Head and Neck Cancers - Molecular Biology


Literature Analysis

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Tag cloud generated 10 March, 2017 using data from PubMed, MeSH and CancerIndex

Mutated Genes and Abnormal Protein Expression (46)

How to use this data tableClicking on the Gene or Topic will take you to a separate more detailed page. Sort this list by clicking on a column heading e.g. 'Gene' or 'Topic'.

CDKN2A 9p21.3 ARF, MLM, P14, P16, P19, CMM2, INK4, MTS1, TP16, CDK4I, CDKN2, INK4A, MTS-1, P14ARF, P19ARF, P16INK4, P16INK4A, P16-INK4A Prognostic
-CDKN2A Mutations in Head and Neck Cancer
GSTM1 1p13.3 MU, H-B, GST1, GTH4, GTM1, MU-1, GSTM1-1, GSTM1a-1a, GSTM1b-1b -GSTM1 and Head and Neck Cancers
GSTT1 22q11.23 -GSTT1 Polymorphisms and Head and Neck Cancer
PTGS2 1q25.2-q25.3 COX2, COX-2, PHS-2, PGG/HS, PGHS-2, hCox-2, GRIPGHS -PTSG2 (COX2) and Head and Neck Squamous Carcinoma
SDHD 11q23.1 PGL, CBT1, CWS3, PGL1, QPs3, SDH4, cybS, CII-4 -SDHD and Head and Neck Cancers
ALDH2 12q24.2 ALDM, ALDHI, ALDH-E2 -ALDH2 and Head and Neck Cancers
SDHB 1p36.1-p35 IP, SDH, CWS2, PGL4, SDH1, SDH2, SDHIP -SDHB and Head and Neck Cancers
NOTCH1 9q34.3 hN1, AOS5, TAN1, AOVD1 -NOTCH1 mutations in Head and Neck Cancers
TP63 3q28 AIS, KET, LMS, NBP, RHS, p40, p51, p63, EEC3, OFC8, p73H, p73L, SHFM4, TP53L, TP73L, p53CP, TP53CP, B(p51A), B(p51B) -TP63 and Head and Neck Cancers
SDHC 1q23.3 CYBL, PGL3, QPS1, SDH3, CYB560 -SDHC and Head and Neck Cancers
ADH1B 4q23 ADH2, HEL-S-117 -ADH1B and Head and Neck Cancers
MIR21 17q23.1 MIRN21, miR-21, miRNA21, hsa-mir-21 -MicroRNA miR-21 and Head and Neck Cancer
XRCC3 14q32.3 CMM6 -XRCC3 and Head and Neck Cancers
CTTN 11q13.3 EMS1 -CTTN and Head and Neck Cancers
VHL 3p25.3 RCA1, VHL1, pVHL, HRCA1 -VHL and Head and Neck Cancers
ADH1C 4q23 ADH3 -ADH1C and Head and Neck Cancers
OGG1 3p26.2 HMMH, MUTM, OGH1, HOGG1 -OGG1 and Head and Neck Cancers
CKAP4 12q23.3 p63, CLIMP-63, ERGIC-63 -CKAP4 and Head and Neck Cancers
NFIB 9p24.1 CTF, NF1-B, NFI-B, NFIB2, NFIB3, NF-I/B, NFI-RED, HMGIC/NFIB -NFIB and Head and Neck Cancers
CCNA1 13q12.3-q13 CT146 -CCNA1 and Head and Neck Cancers
PGLS 19p13.2 6PGL -PGLS and Head and Neck Cancers
SDHAF2 11q12.2 PGL2, SDH5, C11orf79 -SDHAF2 and Head and Neck Cancers
S100A2 1q21 CAN19, S100L -S100A2 and Head and Neck Cancers
CCR7 17q12-q21.2 BLR2, EBI1, CCR-7, CD197, CDw197, CMKBR7, CC-CKR-7 -CCR7 and Head and Neck Cancers
ERCC4 16p13.12 XPF, RAD1, FANCQ, ERCC11 -ERCC4 and Head and Neck Cancers
SDHA 5p15 FP, PGL5, SDH1, SDH2, SDHF, CMD1GG -SDHA and Head and Neck Cancers
TMEM127 2q11.2 -TMEM127 and Head and Neck Cancers
SLC5A8 12q23.1 AIT, SMCT, SMCT1 -SLC5A8 and Head and Neck Cancers
CIC 19q13.2 -CIC and Head and Neck Cancers
MTHFD1 14q24 MTHFC, MTHFD -MTHFD1 and Head and Neck Cancers
ADAM17 2p25 CSVP, TACE, NISBD, ADAM18, CD156B, NISBD1 -ADAM17 and Head and Neck Cancers
MAGEB2 Xp21.3 DAM6, CT3.2, MAGE-XP-2 -MAGEB2 and Head and Neck Cancers
CCL19 9p13 ELC, CKb11, MIP3B, MIP-3b, SCYA19 -CCL19 and Head and Neck Cancers
FAT1 4q35 FAT, ME5, CDHF7, CDHR8, hFat1 -FAT1 and Head and Neck Cancers
CYP2A13 19q13.2 CPAD, CYP2A, CYPIIA13 -CYP2A13 and Head and Neck Cancers
CSMD1 8p23.2 PPP1R24 -CSMD1 and Head and Neck Cancers
CD3D 11q23.3 T3D, IMD19, CD3-DELTA -CD3D and Head and Neck Cancers
ING3 7q31 Eaf4, ING2, MEAF4, p47ING3 -ING3 and Head and Neck Cancers
LIMD1 3p21.3 -LIMD1 and Head and Neck Cancers
SPECC1 17p11.2 NSP, CYTSB, HCMOGT1, HCMOGT-1 -SPECC1 and Head and Neck Cancers
MIR1271 5q35 MIRN1271, hsa-mir-1271 -MIRN1271 microRNA, human and Head and Neck Cancers
RHOBTB2 8p21.3 DBC2 -RHOBTB2 and Head and Neck Cancers
RNF213 17q25.3 ALO17, MYMY2, MYSTR, NET57, C17orf27, KIAA1618 -RNF213 and Head and Neck Cancers
KLK10 19q13 NES1, PRSSL1 -KLK10 and Tongue Neoplasms
PCSK7 11q23.3 LPC, PC7, PC8, SPC7 -PCSK7 and Head and Neck Cancers

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications

Chen X, Hu H, Liu J, et al.
FOXF2 promoter methylation is associated with prognosis in esophageal squamous cell carcinoma.
Tumour Biol. 2017; 39(2):1010428317692230 [PubMed] Related Publications
Esophageal squamous cell carcinoma is a commonly malignant tumor of digestive tract with poor prognosis. Previous studies suggested that forkhead box F2 ( FOXF2) could be a candidate gene for assessing and predicting the prognosis of human cancers. However, the relationship between FOXF2 promoter methylation and the prognosis of esophageal squamous cell carcinoma remained unclear. Formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma tissues of 135 esophageal squamous cell carcinoma patients were detected for FOXF2 promoter methylation status by methylation-specific polymerase chain reaction approach. DNA methylation results were evaluated with regard to clinicopathological features and overall survival. Our study confirmed that FOXF2 promoter hypermethylation could independently predict a poorer overall survival of esophageal squamous cell carcinoma patients ( p = 0.002), which was consistent with the data mining results of the data from 82 esophageal squamous cell carcinoma patients in The Cancer Genome Atlas datasets ( p = 0.036). In addition, no correlation was found between FOXF2 promoter methylation and other clinic pathological parameters (age, gender, differentiation, lymph node metastasis, stage, cutting edge, vascular invasion, smoking behavior, and drinking history). In conclusion, FOXF2 methylation might be a useful prognostic biomarker for esophageal squamous cell carcinoma patients.

Vrana D, Matzenauer M, Aujesky R, et al.
Potential Predictive Role of MicroRNAs in the Neoadjuvant Treatment of Esophageal Cancer.
Anticancer Res. 2017; 37(2):403-412 [PubMed] Related Publications
Esophageal cancer is a disease with disappointing prognosis. Currently, there are no predictive factors that can identify patients who on the one hand would likely benefit from tri-modality management and, on the other hand, would not be significantly affected by the morbidity accompanying the treatment. MicroRNAs are short non-coding RNAs responsible for post-transcriptional modification of gene expression by binding to 3'-UTR of messenger RNA and represent emerging potential predictive biomarkers of treatment (chemotherapy and radiotherapy) efficacy and toxicity. We reviewed the current literature, addressing the potential predictive role of microRNAs for efficacy of chemotherapy (specifically cisplatin, 5-fluorouracil, doxorubicin and paclitaxel) and radiotherapy, including predicted targets in the cell. Altogether 82 articles were identified and included in this review. This may be the first review on this topic specifically focusing on neoadjuvant treatment of esophageal cancer.

Hsieh R, Nico MM, Camillo CM, et al.
Mutational Status of NRAS and BRAF Genes and Protein Expression Analysis in a Series of Primary Oral Mucosal Melanoma.
Am J Dermatopathol. 2017; 39(2):104-110 [PubMed] Related Publications
Primary oral mucosal melanoma is an extremely rare and aggressive tumor arising from melanocytes located in the mucosal epithelium of the oral cavity. Although malignant melanoma of oral mucosa shares some clinical features with its cutaneous counterpart, it has been associated with a worst prognosis; its etiopathogenesis are still only partially unraveled as there is no influence of UV radiation. It is known that the mitogen-activated protein kinase pathway mediates cellular responses to growth signals and its activation is an important phenomenon in melanoma. The aim of this study was to evaluate NRAS and BRAF genes, both components of mitogen-activated protein kinase molecular pathway, and compare with their protein expression. Point mutations of NRAS (codons 12, 13, and 61) and BRAF (codon 600) were screened by pyrosequencing method, and its results were associated to the protein expression of RAS and BRAF performed by immunohistochemistry. The authors observed mutation in BRAF 600 (3/14), NRAS codons 12 and 13 (2/14), and NRAS codon 61 (2/8). One case showed positive RAS protein expression, but no mutation was observed. Twelve in 14 cases showed positive BRAF protein expression: 3 cases showed BRAF mutation; 2 cases showed NRAS codon 61 mutation; 2 cases showed NRAS codons 12 and 13 mutation but not simultaneously. Although NRAS and BRAF mutation frequency and RAS protein expression are low, BRAF protein expression was intense; probably, NRAS and BRAF mutations are independent events and alternative molecular mechanisms in the primary oral mucosal melanoma tumorigenesis.

Liang S, Zhang S, Wang P, et al.
LncRNA, TUG1 regulates the oral squamous cell carcinoma progression possibly via interacting with Wnt/β-catenin signaling.
Gene. 2017; 608:49-57 [PubMed] Related Publications
Oral squamous cell carcinoma (OSCC) is one the most common cancer affecting the head and neck region, and the molecular mechanisms underlying OSCC development is largely unknown. Long non-coding RNAs (lncRNAs) are emerging as key regulators in tumor development. The present study aimed to investigate the role of lncRNA, taurine upregulated gene 1 (TUG1) in OSCC development. The mRNA and protein expression levels were determined by qRT-PCR and western blotting; flow cytometry and ELISA experiments were employed to examine the cell apoptosis; CCK-8 assay, MTT assay, colony formation assay, and cell invasion assay was used to determine cell growth, cell proliferation and cell invasion, respectively. qRT-PCR results showed that TUG1 was up-regulated in both OSCC tissues and cell lines. The high expression level of TUG1 was significantly correlated with TNM stage, lymph node metastasis and tumor grade in OSCC patients. CCK-8 assay, MTT assay, colony formation assay, and cell invasion assay results showed that knock-down of TUG1 by siRNA transfection suppressed cell growth, cell proliferation, and cell invasion in OSCC cell lines (Tca8113 and TSCCA). The cell apoptosis was induced in Tca8113 and TSCCA cells transfected with TUG1 siRNA. In addition, knock-down of TUG1 in Tca8113 and TSCCA cells significantly suppressed the mRNA and protein expression levels of β-catenin, cyclin D1, and c-myc. Wnt/β-catenin pathway activator (LiCl) reversed the TUG1 knock-down effect on cell proliferation, cell invasion and cell apoptosis in Tca8113 and TSCCA cells. In summary, knock-down of TUG1 suppressed cell growth, proliferation and invasion, and also induced apoptosis of OSCC possibly via targeting Wnt/β-catenin signaling. Our data suggest that knock-down of TUG1 may represent a novel therapeutic target for the management of OSCC.

Liu Y, Li H, Zhang J, Gao X
Potassium Iodate Differently Regulates the Proliferation, Migration, and Invasion of Human Thyroid Cancer Cells via Modulating miR-146a.
Cancer Invest. 2017; 35(2):122-128 [PubMed] Related Publications
The effects of different doses of potassium iodate (KIO3) on the malignancy of thyroid cancer were investigated. Results showed that the proliferation, migration, and invasion of SW579 thyroid cancer cells were improved by 10(-6) M KIO3, which was associated with microRNA(miR)-146a deficit; 10(-2) M KIO3 significantly enhanced miR-146a level and suppressed SW579 cell proliferation, migration, and invasion. The diverse effects of KIO3 on SW579 cells were associated with the expression changes in miR-146a targets, Bcl-2, Bax, and caspase-3. Our study concludes that different doses of KIO3 have counteracting effects on the malignancy of thyroid cancer through modulating miR-146a level.

Fendereski M, Zia MF, Shafiee M, et al.
MicroRNA-196a as a Potential Diagnostic Biomarker for Esophageal Squamous Cell Carcinoma.
Cancer Invest. 2017; 35(2):78-84 [PubMed] Related Publications
We observed significant up-regulation of miR-196a in esophageal squamous cell carcinoma (ESCC) as compared with their adjacent normal tissue (p = .002). Receiver operating characteristics curve analysis confirmed the suitability of miR-196a as a potential tumor marker for diagnosis of ESCC. Furthermore, analysis of miR-196a levels in saliva samples determined an average of 27-fold up-regulations in ESCC patients compared with healthy group. Our results suggest that salivary miR-196a may be a suitable noninvasive biomarker for diagnosis of ESCC. In addition, molecular pathway enrichment analysis of microRNA (miR)-196a determined focal adhesion, spliceosome and p53 signaling pathways as the most relevant pathways with miR-196a targetome.

Zhang CZ
Long non-coding RNA FTH1P3 facilitates oral squamous cell carcinoma progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression.
Gene. 2017; 607:47-55 [PubMed] Related Publications
A growing body of evidence has indicated that long non-coding RNAs (lncRNAs) function as competing endogenous RNAs (ceRNAs) during tumorigenesis. In this study, the qRT-PCR results revealed that the lncRNA ferritin heavy chain 1 pseudogene 3 (FTH1P3) was over-expressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. Ectopic expression of FTH1P3 facilitates cell proliferation and colony formation in OSCC cells. Moreover, FTH1P3 acted as a competitive endogenous RNA (ceRNA), effectively becoming sponge for miR-224-5p and thereby modulating the expression of fizzled 5. Importantly, expression analysis revealed that both FTH1P3 and fizzled 5 were up-regulated in OSCC cell lines and tissues, and over-expression of fizzled 5 also functioned as an oncogene in OSCC cells. Our data demonstrated FTH1P3 facilitated OSCC progression by acting as a molecular sponge of miR-224-5p to modulate fizzled 5 expression. Thus, targeting the ceRNA network referring FTH1P3 may be a therapeutic target for treatment of OSCC.

Kern B, Coppin L, Romanet P, et al.
Multiple HABP2 variants in familial papillary thyroid carcinoma: Contribution of a group of "thyroid-checked" controls.
Eur J Med Genet. 2017; 60(3):178-184 [PubMed] Related Publications
A heterozygous germline variant in the HABP2 gene c.1601G > A (p.Gly534Glu), which negatively impacts its tumor suppressive activity in vitro, has been described in 4-14% of kindreds of European-American ancestry with familial papillary thyroid carcinoma (fPTC). But it is also found in ≈4% of Europeans and European/Americans from public databases that, however, did not provide information on the thyroid function of the controls. To get unbiased results, we decided to compare HABP2 genotypes of patients with fPTC with those of "thyroid-checked" controls. A control group consisting of 136 European patients who were thyroidectomised for medullary thyroid carcinoma and devoid of any histologically detectable PTC or follicular-deriving carcinoma was built. In parallel we recruited 20 patients with fPTC from eleven independent European kindreds. The entire coding region of HABP2 was analyzed by Sanger sequencing the germline DNAs of patients. Nucleotide variants were searched for by Snap Shot analysis in the controls. Two variants, c.1601G > A (p.Gly534Glu) and c.364C > T (p.Arg122Trp), were found in 2 and 3 patients at the heterozygous level respectively (minor allele frequency (MAF): 5.0% and 7.5%, respectively). In controls, the MAF was either similar for the c.1601G > A HABP2 variant (2.94%, ns) or significantly lower for the c.364C > T variant (0.73%, p = 0.016). The Arg122 residue lies in the EGF-3 domain of HABP2 which is important for its activation but, however, superposition of the predicted 3D structures of the wild type and mutated proteins suggests that this variant is tolerated at the protein level. In conclusion, our data do not support the pathogenicity of the HABP2 c.1601G > A variant but highlight the existence of a new one that should be more extensively searched for in fPTC patients and its pathogenicity more carefully evaluated.

Wang B, Lv K, Chen W, et al.
miR-375 and miR-205 Regulate the Invasion and Migration of Laryngeal Squamous Cell Carcinoma Synergistically via AKT-Mediated EMT.
Biomed Res Int. 2016; 2016:9652789 [PubMed] Free Access to Full Article Related Publications
Previous studies have found that miR-375 and miR-205 were significantly dysregulated in laryngeal squamous cell carcinoma, which contributed to the invasion and migration of LSCC. However, the mechanisms of miR-375 and miR-205 regulating the invasion and migration of LSCC remain unknown. qRT-PCR was performed in 40 pairs of tissue samples to investigate the expression of miR-375 and miR-205 in LSCC and paracarcinoma tissues. To investigate whether or not miR-375 and miR-205 regulated the invasion and migration of LSCC synergistically via AKT-mediated epithelial-mesenchymal transition, miR-375 mimic and miR-205 inhibitor were transfected into SNU899 cells and miR-375 inhibitor and miR-205 mimic were transfected into SNU899 cells, respectively, with or without AKT inhibitor. Then the expressions of miR-375 and miR-205 were validated by qRT-PCR, cell migration and invasion were determined by wound healing assay and transwell invasive assay, and western blot analysis was performed to detect the expression of related proteins. Our results showed that miR-375 and miR-205 regulated the invasion and migration of LSCC via AKT-mediated EMT synergistically. In conclusion, our findings provided not only new information about the molecular mechanism of miRNAs regulating invasion and migration of LSCC, but also a theoretical principle for potential targeting therapy of laryngeal squamous carcinoma.

Crescenzi A, Fulciniti F, Bongiovanni M, et al.
Detecting N-RAS Q61R Mutated Thyroid Neoplasias by Immunohistochemistry.
Endocr Pathol. 2017; 28(1):71-74 [PubMed] Related Publications
Recently, the immunohistochemistry (IHC) for N-RAS Q61R has been developed and commercialized for clinical practice. Here, we investigated the reliability of IHC to identify N-RAS Q61R mutated thyroid neoplasia. A series of 24 consecutive thyroid lesions undergone surgery following indeterminate cytology were enrolled. Paraffin sections were stained for IHC using the rabbit monoclonal anti-human N-RAS Q61R, clone SP174. N-RAS mutations in codon 61 were also investigated by automated sequencing. At histology, 12 cases of follicular carcinoma, cytologically defined as follicular lesions, 1 papillary cancer, 7 follicular adenomas, and 4 hyperplastic nodules were found. Of these, 4 showed a positive IHC for anti N-RAS antibody where N-RAS expression was detected mainly at cytoplasmic level with similar intensity of reaction. The remaining cases had negative IHC. A 100% concordance between IHC and molecular analysis for N-RAS Q61R was observed. In conclusion, this study shows high reliability of IHC to identify N-RAS Q61R mutated thyroid lesions with high cost-effectiveness. These data indicate the reliability of IHC to identify N-RAS Q61R mutated thyroid neoplasia and suggest to adopt this approach for a more accurate management of patients, when indicated.

Meng LZ, Fang JG, Sun JW, et al.
Aberrant Expression Profile of Long Noncoding RNA in Human Sinonasal Squamous Cell Carcinoma by Microarray Analysis.
Biomed Res Int. 2016; 2016:1095710 [PubMed] Free Access to Full Article Related Publications
Objectives. This study aimed to identify aberrantly expressed long noncoding RNAs (lncRNAs) profile of sinonasal squamous cell carcinoma (SSCC) and explore their potential functions. Methods. We investigated lncRNA and mRNA expression in SSCC and paired adjacent noncancerous tissues obtained from 6 patients with microarrays. Gene ontology (GO) analysis and pathway analysis were utilized to investigate the gene function. Gene signal-network and lncRNA-mRNA network were depicted. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to validate 5 lncRNAs in a second set of paired SSCC and adjacent noncancerous tissues obtained from 22 additional patients. Results. We identified significantly differentially expressed lncRNAs (n = 3146) and mRNAs (n = 2208) in SSCC relative to noncancerous tissues. The GO annotation indicated that there are some core gene products that may be attributed to the progress of SSCC. The pathway analysis identified many pathways associated with cancer. The results of lncRNA-mRNA network and gene signal-network implied some core lncRNAs/mRNAs might play important roles in SSCC pathogenesis. The results of qRT-PCR showed that all of the 5 lncRNAs were differentially expressed and consistent with the microarray results. Conclusion. Our study is the first screening and analysis of lncRNAs expression profile in SSCC and may offer new insights into pathogenesis of this disease.

Chen P, Shan Z, Zhao J, et al.
NFAT1 promotes cell motility through MMP-3 in esophageal squamous cell carcinoma.
Biomed Pharmacother. 2017; 86:541-546 [PubMed] Related Publications
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors and the prognosis of patients remains poor. Increasing evidence suggests that nuclear factor of activated T cell (NFAT1) plays an important role in the development and progression of cancers. Herein, we show that NFAT1 was overexpressed in human ESCC, which was significantly associated with advanced tumor stage and lymph node metastasis. Functional studies found that NFAT1 silencing could suppress cell migration and invasion through MMP-3. The data therefore suggest that NFAT1 plays an important adverse role in the development and progression of ESCC, implicating possible application in clinics as a biomarker and a potential new therapeutic target.

Wang YL, Gong WG, Yuan QL
Effects of miR-27a upregulation on thyroid cancer cells migration, invasion, and angiogenesis.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Thyroid cancer is the most common type of endocrine tumor. MicroRNAs (miRNAs) play a critical role in a variety of diseases, especially cancer occurrence and progression. However, the specific mechanism by which miRNAs trigger disease states has not been fully elucidated. This study aims to investigate the role of miR-27a in thyroid cancer cells. A wound healing assay was adopted to examine cell migration. A transwell assay was applied to assess cell invasion. A thyroid cancer xenograft model was established using BALB/c nude mice. Western blot was performed to quantify iNOS expression. Tumor tissue blood vessel density was evaluated via immunohistochemistry assays. The results indicated that miR-27a downregulation inhibited thyroid cancer cell migration, while upregulation of miR-27a promoted thyroid cancer cell migration (P < 0.05). Furthermore, reduction in miR-27a expression suppressed thyroid cancer cell invasion (P < 0.05). In the nude mouse model of thyroid cancer xenograft, upregulation of miR-27 induced iNOS expression in pathological tumor tissues, whereas miR-27a inhibition resulted in the opposite effect (P < 0.05). CD105 level was also significantly increased during miR-27a upregulation, and was declined when miR-27a was inhibited (P < 0.05). In conclusion, miR-27a upregulation in thyroid cancer cells affects tumor cell migration, invasion, and angiogenesis by targeting downstream genes. Therefore, miR27a may act as a biomarker of thyroid cancer.

Laytragoon-Lewin N, Cederblad L, Andersson BÅ, et al.
Single-Nucleotide Polymorphisms and Cancer Risk, Tumor Recurrence, or Survival of Head and Neck Cancer Patients.
Oncology. 2017; 92(3):161-169 [PubMed] Related Publications
OBJECTIVE: This paper aims at studying the influence of single-nucleotide polymorphisms (SNPs) on cancer risk, tumor recurrence, and survival in head and neck (H&N) cancer patients.
METHODS: A total of 45 SNPs in 41 genes were investigated. A total of 174 Caucasian H&N cancer patients and 245 healthy blood donors were enrolled in the study.
RESULTS: Ten SNPs were associated with H&N cancer risk, but the identified SNPs differed among males and females. Some of the SNPs were related to immune response genes. The immune response gene SNPs were also related to survival. In particular, we noted that the tumor necrosis factor alpha (TNFα) rs1800629 could have an influence on cancer risk, tumor recurrence as well as survival.
CONCLUSION: Genetic variation of the TNFα rs1800629 might be useful as a biomarker in clinical decision-making since it was found to be related to cancer risk, tumor recurrence, and survival of H&N cancer patients.

Zhang H, Zhao JH, Suo ZM
Knockdown of HOXA5 inhibits the tumorigenesis in esophageal squamous cell cancer.
Biomed Pharmacother. 2017; 86:149-154 [PubMed] Related Publications
Homeobox A5 (HOXA5) is a member of the homeobox (HOX) family and was upregulated in many types of tumors. However, its expression and role in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, the aim of this study was to investigate the expression and function of HOXA5 in ESCC. Our results showed that HOXA5 was highly expressed in ESCC cell lines. The in vitro experiments demonstrated that knockdown of HOXA5 significantly inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, the in vivo experiments showed that knockdown of HOXA5 significantly inhibited the tumor growth of ESCC in mice xenograft model. Finally, sh-HOXA5 inhibited the expression of β-catenin, cyclin D1 and c-Myc in ESCC cells. Taken together, these data revealed that knockdown of HOXA5 suppressed the proliferation and metastasis partly by interfering with Wnt/β-catenin signaling pathway in ESCC cells. Therefore, these findings suggest that HOXA5 may be a potential therapeutic target for the treatment of ESCC.

Xu CZ, Jiang C, Wu Q, et al.
A Feed-Forward Regulatory Loop between HuR and the Long Noncoding RNA HOTAIR Promotes Head and Neck Squamous Cell Carcinoma Progression and Metastasis.
Cell Physiol Biochem. 2016; 40(5):1039-1051 [PubMed] Related Publications
BACKGROUND/AIMS: The lncRNA Homeobox (HOX) transcript antisense RNA (HOTAIR) is overexpressed in numerous cancers. HuR is also overexpressed during tumourigenesis and is abnormally present within the cytoplasm, where it binds to AU-rich elements in the 3'UTRs of target mRNA and post-transcriptionally regulates the expression of its target genes. However, whether HOTAIR is regulated and the mechanisms by which it affects head and neck squamous cell carcinoma (HNSCC) are not well understood.
METHODS: MTT, cell cycle arrest and apoptotic assays were used to examine the effects of HOTAIR and HuR on cell viability in SCC25 and FaDu cells. Wound healing and transwell invasion analysis were performed to detect the effects of HOTAIR and HuR on cell migration and invasion. The interaction between HuR and HOTAIR was confirmed via qRT-PCR, western blots, luciferase reporter and RIP assays. Finally, qRT-PCR analysis was used to detect the levels of HuR and HOTAIR in HNSCC tumours and adjacent normal tissues.
RESULTS: Knockdown of HOTAIR and HuR decreased cell viability, cellular migration and invasion. Moreover, HuR interacted and stabilized HOTAIR stability and thus promoted HOTAIR expression. Notably, HOTAIR acted as a miRNA sponge for HuR. HuR also reinforced HOTAIR sponge activity through miRNA recruitment, thus enhancing HuR expression in turn. Finally, HuR and HOTAIR levels were positively correlated and significantly up-regulated in tumours samples.
CONCLUSION: We demonstrated the existence of a regulatory loop in which the expression of HOTAIR and HuR is reciprocally and temporally regulated during the metastasis and progression of HNSCC.

Otsuka Y, Sato H, Oikawa T, et al.
High expression of EPB41L5, an integral component of the Arf6-driven mesenchymal program, correlates with poor prognosis of squamous cell carcinoma of the tongue.
Cell Commun Signal. 2016; 14(1):28 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Squamous cell carcinoma of the tongue (tongue SCC) is a major subtype of head and neck squamous cell carcinoma (HNSCC), which is an intractable cancer under current therapeutics. ARF6 and its effector AMAP1 are often overexpressed in different types of cancers, such as breast cancer and renal cancer, and in these cancers, AMAP1 binds to EPB41L5 to promote invasion, metastasis, and drug resistance. EPB41L5 is a mesenchymal-specific protein, normally induced during epithelial-mesenchymal transition (EMT) to promote focal adhesion dynamics. Similarly to breast cancer and renal cancer, the acquisition of mesenchymal phenotypes is the key process that drives the malignancy of HNSCC. We previously showed that the overexpression of AMAP1 in tongue SCC is statistically correlated with the poor outcome of patients. In this study, we examined whether tongue SCC also expresses EPB41L5 at high levels.
RESULTS: Immunohistochemical staining of clinical specimens of tongue SCC demonstrated that high expression levels of EPB41L5 statistically correlate with poor disease-free survival and poor overall survival rates of patients. The tongue SCC cell line SCC-9, which overexpress Arf6 and AMAP1, also expressed EPB41L5 at high levels to promote invasiveness, whereas the weakly invasive SCC-25 cells did not express EPB41L5 at notable levels. Among the different EMT-associated transcriptional factors, ZEB1 was previously found to be most crucial in inducing EPB41L5 in breast cancer and renal cancer. In contrast, expression levels of ZEB1 did not correlate with the expression levels of EPB41L5 in tongue SCC, whereas KLF8 and FOXO3 levels showed positive correlations with EPB41L5 levels. Moreover, silencing of EPB41L5 only marginally improved the drug resistance of SCC-9 cells, even when coupled with ionizing radiation.
CONCLUSION: Our results indicate that activation of the cancer mesenchymal program in tongue SCC, which leads to EPB41L5 expression, closely correlates with the poor prognosis of patients. However, ZEB1 was not the major inducer of EPB41L5 in tongue SCC, unlike in breast cancer and renal cancer. Thus, processes that trigger the mesenchymal program of tongue SCC, which drives their malignancies, seem to be substantially different from those of other cancers.

Jili S, Eryong L, Lijuan L, Chao Z
RUNX3 inhibits laryngeal squamous cell carcinoma malignancy under the regulation of miR-148a-3p/DNMT1 axis.
Cell Biochem Funct. 2016; 34(8):597-605 [PubMed] Related Publications
Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. Runt-related transcription factor 3 (RUNX3), an important tumor suppressor, is known to related to lymph node metastasis and the development of LSCC. However, the biological roles and potential mechanisms RUNX3 expression was not well understood. In this study, we reported that the RUNX3 was significantly downregulated and highly methylated in LSCC compared with their matched normal. The enforced expression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. We identified that RUNX3 was regulated by miR-148a-3p and found that the expression level of miR-148-3p was significantly decreased and positively related with the expression of RUNX3 in LSCC. We also identified that DNA methyltransferase enzyme DNA (cytosine-5-)-methyltransferase 1 (DNMT1) was targeted by miR-148a-3p in LSCC. The knockdown of DNMT1 promoted the expression of RUNX3 and inhibited migration, invasion, and proliferation in LSCC cells. In summary, our study demonstrated that miR-148a-3p may regulate RUNX3 expression through the modulation of DNMT1-dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC. LSCC is a highly aggressive malignant cancer and accounts for 1% to 2% of all malignancies diagnosed worldwide. In this study, we reported that RUNX3, an important tumor suppressor, was significantly downregulated and highly methylated in LSCC compared with their matched normal. The overexpression of RUNX3 inhibited LSCC cell migration, invasion, and proliferation, whereas the inhibition of RUNX3 did the opposite. Moreover, RUNX3 was regulated by miR-148a-3p, which targeted DNA methyltransferase enzyme DNMT1 in LSCC cells. Therefore, miR-148a-3p may regulate RUNX3 expression through the modulation of DNMT1-dependent DNA methylation in LSCC, providing a novel target and a potential therapeutic pathway against LSCC.

Hu HB, Jie HY, Zheng XX
Three Circulating LncRNA Predict Early Progress of Esophageal Squamous Cell Carcinoma.
Cell Physiol Biochem. 2016; 40(1-2):117-125 [PubMed] Related Publications
BACKGROUND/AIMS: Previous studies revealed that circulating (either from plasma or serum) long non-coding RNA may predict the occurrence or prognosis of multiple human malignant tumors. In this study, we mainly explored whether circulating lncRNAs can be utilized as biomarkers predicting the development of human esophageal squamous cell carcinoma (ESCC).
METHODS: LncRNA microarray was applied to screen the potential biomarkers for ESCC. Each group contained three individual plasma samples. A multi-stage validation and risk score formula detection were used for validation.
RESULTS: Eleven dysregulated lncRNAs were obtained after Venny analysis. Further validation in a larger cohort including 205 ESCC patients, 82 patients suffering from esophagus dysplasia and 210 healthy controls confirmed that increased Linc00152, CFLAR-AS1 and POU3F3 might be potential biomarkers for predicting the early progress with an area under curve (AUC) of 0.698, 0.651 and 0.584, respectively. The merged AUC of the three factors and merged with CEA was 0.765 and 0.955, respectively. We also revealed that circulating levels of three lncRNAs were associated with poor post-surgery prognosis of ESCC patients.
CONCLUSIONS: The three circulating lncRNAs might serve as potential biomarkers for predicting the early occurrence of ESCC.

Song W, Zou SB
Prognostic role of lncRNA HOTAIR in esophageal squamous cell carcinoma.
Clin Chim Acta. 2016; 463:169-173 [PubMed] Related Publications
BACKGROUND: HOX transcript antisense intergenic RNA (HOTAIR) may be implicated in cancer development and progression. Clinical studies have suggested that HOTAIR may be related to poor prognosis in esophageal squamous cell carcinoma (ESCC). This study was designed to clarify the prognostic role of HOTAIR in ESCC.
METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) databases were searched to identify studies evaluating the prognostic significance of HOTAIR in ESCC. Pooled hazard ratios (HRs) for overall survival (OS), lymph node metastasis (LNM), and cancer stage were calculated using fixed-effects/random-effects models.
RESULTS: A total of 510 patients from five studies were included. Meta-analysis revealed that high HOTAIR expression was significantly correlated with poor OS (HR, 2.37; 95% CI, 1.80-3.11; P<0.00001) and positive LNM (RR, 1.96; 95% CI, 1.07-3.60; P=0.03).
CONCLUSION: Elevated lncRNA HOTAIR indicated a poor prognosis for patients with ESCC, and it may also have predictive potential for ESCC metastasis.

Wang Y, Chen C, Wang X, et al.
Lower DSC1 expression is related to the poor differentiation and prognosis of head and neck squamous cell carcinoma (HNSCC).
J Cancer Res Clin Oncol. 2016; 142(12):2461-2468 [PubMed] Related Publications
PURPOSE: Although desmocollins have an important position in cancer-related research, there are little reports about the relations between cancers and desmocollin 1 (DSC1). The present study was designed to investigate the correlations between DSC1 and head and neck squamous cell carcinoma (HNSCC).
METHODS: First we analyzed the GEO database; then, HNSCC and pericarcinous tissues were collected to verify the results. DSC1 expression was detected by western blot and real-time PCR. The co-expression genes of DSC1 were extracted from Cancer Cell Line Encyclopedia database (CCLE database), and their correlation was analyzed in The Cancer Genome Atlas HNSCC database (TCGA HNSCC database). Next the gene ontology analysis (GO) was carried out. Moreover, we suppressed DSC1 in FaDu cell to investigate the internal mechanism.
RESULTS: GEO database showed that DSC1 was higher in HNSCC and patients with higher DSC1 had unfavorable prognosis. The results of the samples showed that DSC1 was significantly higher in HNSCC than in normal tissue, which was consistent with the results of GEO database. The co-expression genes of DSC1 were extracted from CCLE database and verified in TCGA HNSCC database. It revealed that DSC1 was related to cell signal transduction. In FaDu/siDSC1 cells, the proliferation and migration were decreased compared to FaDu cells, and the expression levels of β-catenin, c-myc and cyclin D1 down-regulated significantly.
CONCLUSIONS: The increased expression of DSC1 can promote the occurrence of HNSCC and is associated with tumor. The increased expression of DSC1 also indicates a poor prognosis of the patients with HNSCC.

Song JH, Han YM, Kim WH, et al.
Oxidative stress from reflux esophagitis to esophageal cancer: the alleviation with antioxidants.
Free Radic Res. 2016; 50(10):1071-1079 [PubMed] Related Publications
The incidence of reflux esophagitis increases in world, affecting approximately 20% of Western populations and its consequent lesion, Barrett's esophagus (BE), established as the primary precursor lesion of esophageal adenocarcinoma (EAC) or Barrett associated adenocarcinoma (BAA), is also increasing in incidence in Asian countries as well as Western countries. The fact that surveillance strategies have not had a major benefit in decreasing the incidence of EAC increased attention to arrest or delay the progression of BE to EAC. Since sustained inflammation and consequent oxidative stress plays core pathogenic role in reflux esophagitis, BE, and BAA, attention paid to anti-inflammatory and antioxidative agents in the treatment of reflux esophagitis. Since the risk of esophagitis is associated with hiatal hernia, body mass index, and duodenogastric reflux, and acid exposure, lifestyle modification and agents to control gastric acidity might be mainstay for treatment, but several studies consistently showed the implication of robust oxidative stress in reflux associated esophageal diseases. In this review article, the pathogenic implication of oxidative stress will be introduced in the development of reflux esophagitis, BE, and EAC. Also, since there is great interest in complete healing of reflux esophagitis and chemoprevention to prevent or slow malignant transformation, the contribution of antioxidants or antioxidative agents, which was delivered during SFRR-Asia 2015 (Chiangmai, Thailand), will be described. Also, the molecular mechanisms how the antioxidative drugs, rebamipide, ecabet sodium, and pantoprazole exerted significant protection from acids or bile acids-associated esophagitis are included.

Wu WQ, Zhang LS, Liao SP, et al.
Association between XRCC1 polymorphisms and laryngeal cancer susceptibility in a Chinese sample population.
Genet Mol Res. 2016; 15(4) [PubMed] Related Publications
Laryngeal cancer is the major malignant tumor affecting the upper respiratory tract. Previous studies have reported on the association between XRCC1 genetic polymorphisms and risk of laryngeal cancer, but with conflicting results. In this study, we attempted to assess the association between XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms and risk of laryngeal cancer in a Chinese population. A total of 126 laryngeal cancer patients and 254 control subjects were recruited to this study from the Second Medical College of Jinan University between December 2013 and May 2015. The XRCC1 Arg194Trp, Arg280His, and Arg399Gln polymorphic sites were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Our results revealed a significant association between the AA genotype of XRCC1 Arg280His [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.29-4.87, P = 0.01] and an increased risk of laryngeal cancer susceptibility compared to the GG genotype. Moreover, the A allele showed a higher risk of laryngeal cancer susceptibility compared to the G allele (OR = 1.63, 95%CI = 1.19-2.50, P = 0.002). In conclusion, the results of our study suggest that the AA genotype and A allele of the XRCC1 Arg280His polymorphism are associated with an increased laryngeal cancer risk in a Chinese population.

Kamata YU, Sumida T, Kobayashi Y, et al.
Introduction of ID2 Enhances Invasiveness in ID2-null Oral Squamous Cell Carcinoma Cells via the SNAIL Axis.
Cancer Genomics Proteomics. 2016 11-12; 13(6):493-497 [PubMed] Free Access to Full Article Related Publications
AIM: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells.
MATERIALS AND METHODS: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP).
RESULTS: ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1).
CONCLUSION: ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2-SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC.

Juodzbalys G, Kasradze D, Cicciù M, et al.
Modern molecular biomarkers of head and neck cancer. Part I. Epigenetic diagnostics and prognostics: Systematic review.
Cancer Biomark. 2016; 17(4):487-502 [PubMed] Related Publications
INTRODUCTION: Nearly half of the head and neck cancer cases are diagnosed in late stages. Traditional screening modalities have many disadvantages. The aim of the present article was to review the scientific literature about novel head and neck cancer diagnostics - epigenetic biomarkers.
EVIDENCE ACQUISITION: A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015.
EVIDENCE SYNTHESIS: A total of thirty three relevant studies were included in the review. Fifteen of them concerned DNA methylation alterations, nine evaluation of abundancies in histone expressions and nine miRNA expression changes in HNC.
CONCLUSIONS: Considerable number of epigenetic biomarkers have been identified in both tumor tissue and salivary samples. Genes with best diagnostic effectiveness rates and further studying prospects were: TIMP3, DCC, DAPK, CDH1, CCNA1, AIM1, MGMT, HIC1, PAX1, PAX5, ZIC4, p16, EDNRB, KIF1A, MINT31, CD44, RARβ , ECAD. Individual histone and miRNA alterations tend to be hnc specific. Prognostic values of separate biomarkers are ambiguous. No established standards for molecular assay of head and neck cancer was found in order to elude the paradoxical results and discrepancies in separate trials.

Liu W, Dong Z, Liang J, et al.
Downregulation of Potential Tumor Suppressor miR-203a by Promoter Methylation Contributes to the Invasiveness of Gastric Cardia Adenocarcinoma.
Cancer Invest. 2016; 34(10):506-516 [PubMed] Related Publications
Like many tumor suppressor genes, some miRNA genes harboring CpG islands undergo methylation-mediated silencing. In the study, we found significant downregulation and proximal promoter methylation of miR-203a and miR-203b in gastric cardia adenocarcinoma (GCA) tissues. The methylation status of miR-203a and miR-203b in tumor tissues was negatively correlated with their expression level. GCA patients in stage III and IV with reduced expression or hypermethylation of miR-203a demonstrated poor patient survival. In all, miR-203a and miR-203b may function as tumor suppressive miRNAs, and reactivation of miR-203a may have therapeutic potential and may be used as prognostic marker for GCA patients.

Zhuo X, Song J, Liao J, et al.
Does CYP2E1 RsaI/PstI polymorphism confer head and neck carcinoma susceptibility?: A meta-analysis based on 43 studies.
Medicine (Baltimore). 2016; 95(43):e5156 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Previous reports showed that CYP2E1 RsaI/PstI polymorphism may be a risk factor for cancers. Published meta-analyses in 2010 and 2011, respectively, on the relationship of CYP2E1 RsaI/PstI polymorphisms with the susceptibility to head and neck carcinoma (HNC) have generated inconsistent results. Thus, this study aimed to conduct an updated meta-analysis involving published studies up to Nov 2015 to get a more confidential result.
METHODS: Eligible studies up to Nov 2015 were retrieved and screened. Data were extracted and a quantitative meta-analysis was conducted. Subgroup analyses on ethnicity, source of controls, sample size, genotyping method, smoking status, and drinking status were also performed.
RESULTS: Forty-one publications including a total of 43 case-control studies were selected for analysis. The overall data under a homozygote comparison model indicated a significant association of CYP2E1 RsaI/PstI polymorphisms with HNC risk (c2c2 vs c1c1: odds ratio [OR] = 1.97; 95% confidence interval [CI] = 1.53-2.53). Similar results were observed in the Asian subgroup (c2c2 vs c1c1: OR = 1.98; 95%CI = 1.51-2.60; c2 vs c1: OR = 1.20; 95%CI = 1.03-1.39) and mixed population (c2 vs c1: OR = 1.41; 95%CI = 1.06-1.86) when the data were stratified by ethnicities. Interestingly, increased cancer risk only was shown among never-smokers (c2c2+c1c2 vs c1c1: OR = 1.44; 95%CI = 1.05-1.98) but not ever-smokers.
CONCLUSION: CYP2E1 RsaI/PstI polymorphisms may modify the susceptibility to HNC, particularly among Asians, mixed population, and never-smokers. Future large and well-designed studies are needed to verify this conclusion.

Qiu W, Yang Z, Fan Y, Zheng Q
ZNRF3 is downregulated in papillary thyroid carcinoma and suppresses the proliferation and invasion of papillary thyroid cancer cells.
Tumour Biol. 2016; 37(9):12665-12672 [PubMed] Related Publications
Zinc and ring finger 3 (ZNRF3) is a transmembrane E3 ubiquitin ligase that has emerged as an important regulator of cancer development; however, its cancer-related function remains controversial. Here, we investigated the possible role of ZNRF3 in thyroid carcinoma (TC). We found that ZNRF3 is downregulated in papillary thyroid carcinoma (PTC) compared to normal thyroid tissues and inversely correlated with the degree of cell differentiation. Overexpression of ZNRF3 significantly suppressed cell malignant behaviors, including cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Consistent with recent studies showing that ZNRF3 is involved in the Wnt/β-catenin pathway, ZNRF3 overexpression negatively regulated β-catenin activation, modulating PTC cell behaviors. Clinical specimens revealed a significant inverse correlation between ZNRF3 and β-catenin mRNA levels. Taken together, these results provide insight into a potential tumor suppressor role of ZNRF3 in PTC progression, and may have potential clinical relevance for the prognosis and treatment of PTC.

Hudcova K, Raudenska M, Gumulec J, et al.
Expression profiles of miR-29c, miR-200b and miR-375 in tumour and tumour-adjacent tissues of head and neck cancers.
Tumour Biol. 2016; 37(9):12627-12633 [PubMed] Related Publications
Altered expression of microRNAs (miRNAs) has been shown in many types of malignancies including the head and neck squamous cell carcinoma (HNSCC). Although there are many new and innovative approaches in the treatment of HNSCC, a clear marker of this disease is still missing. Three candidate miRNAs (miR-29c-3p, miR-200b-5p and miR-375-3p) were studied in connection with HNSCC using quantitative real-time PCR expression levels in 42 tissue samples of HNSCC patients and histologically normal tumour-adjacent tissue samples of these patients. Primary HNSCC carcinoma tissues can be distinguished from histologically normal-matched noncancerous tumour-adjacent tissues based on hsa-miR-375-3p expression (sensitivity 87.5 %, specificity 65 %). Additionally, a significant decrease of hsa-miR-200b-5p expression was revealed in tumour-adjacent tissue samples of patients with node positivity. Lower expression of hsa-miR-200b-5p and hsa-miR-29c-3p in HNSCC tumour tissue was associated with higher tumour grade. Consequently, survival analysis was performed. Lower expression of hsa-miR-29c-3p in tumour-adjacent tissue was associated with worse overall and disease-specific survivals. Lower expression of miR-29c-3p in tumourous tissue was associated with worse relapse-free survival. hsa-miR-375-3p seems to be a relatively promising diagnostic marker in HNSCC but is not suitable for prognosis of patients. Furthermore, this study highlighted the importance of histologically normal tumour-adjacent tissue in HNSCC progress (significant decrease of hsa-miR-200b-5p expression in tumour-adjacent tissue of patients with node positivity and low expression of hsa-miR-29c-3p in HNSCC tumour-adjacent tissue associated with worse prognosis).

Samsonov R, Burdakov V, Shtam T, et al.
Plasma exosomal miR-21 and miR-181a differentiates follicular from papillary thyroid cancer.
Tumour Biol. 2016; 37(9):12011-12021 [PubMed] Related Publications
Thyroid cancer (TC) is the most common endocrine malignancy and its incidence has increased over the last few decades. As has been revealed by a number of studies, TC tissue's micro-RNA (miRNA) profile may reflect histological features and the clinical behavior of tumor. However, alteration of the miRNA profile of plasma exosomes associated with TC development has to date not been explored. We isolated exosomes from plasma and assayed their characteristics using laser diffraction particle size analysis, atomic force microscopy, and western blotting. Next, we profiled cancer-associated miRNAs in plasma exosomes obtained from papillary TC patients, before and after surgical removal of the tumor. The diagnostic value of selected miRNAs was evaluated in a large cohort of patients displaying different statuses of thyroid nodule disease. MiRNA assessment was performed by RT-qPCR. In total, 60 patients with different types of thyroid nodal pathology were included in the study. Our results revealed that the development of papillary TC is associated with specific changes in exosomal miRNA profiles; this phenomenon can be used for differential diagnostics. MiRNA-31 was found to be over-represented in the plasma exosomes of patients with papillary TC vs. benign tumors, while miRNA-21 helped to distinguish between benign tumors and follicular TC. MiRNA-21 and MiRNA-181a-5p were found to be expressed reciprocally in the exosomes of patients with papillary and follicular TC, and their comparative assessment may help to distinguish between these types of TC with 100 % sensitivity and 77 % specificity.

Recurring Structural Abnormalities

Selected list of common recurrent structural abnormalities

Abnormality Type Gene(s)
del(13q) in Head and Neck CancersDeletion

This is a highly selective list aiming to capture structural abnormalies which are frequesnt and/or significant in relation to diagnosis, prognosis, and/or characterising specific cancers. For a much more extensive list see the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer.

del(13q) in Head and Neck Cancers

Maestro R, Piccinin S, Doglioni C, et al.
Chromosome 13q deletion mapping in head and neck squamous cell carcinomas: identification of two distinct regions of preferential loss.
Cancer Res. 1996; 56(5):1146-50 [PubMed] Related Publications
Heal and neck squamous cell carcinomas show frequent cytogenetic alterations involving the long arm of chromosome 13. To define the extent of 13q deletions and to identify the minimal areas of chromosome loss, 48 primary squamous cell carcinomas of the head and neck were analyzed for loss of heterozygosity using 11 different polymorphic loci. About 67% of the tumors displayed loss of genetic material at 13q. Most of the cases showed loss of the entire long arm of the chromosome. However, the presence of partial deletions in 10 cases provided evidence of the existence of two preferential sites of chromosome loss at 13q32-ter and 13q14.2-q14.3. The colocalization of the 13q14 minimal region of deletion with the retinoblastoma (RB) gene, which has been proposed as an oncosuppressor in diverse tumor types, prompted us to verify the involvement of this gene in the development of head and neck cancer. No significant variation in RB protein or RB mRNA expression was detected, thus excluding a role for such a gene in the genesis of this type of tumor. Taken together, our data suggest the existence of two new tumor suppressor genes (one close to and one distal to RB), which play a role in the development and/or progression of head and neck squamous cell carcinomas.

Gupta VK, Schmidt AP, Pashia ME, et al.
Multiple regions of deletion on chromosome arm 13q in head-and-neck squamous-cell carcinoma.
Int J Cancer. 1999; 84(5):453-7 [PubMed] Related Publications
Several lines of evidence suggest that the progression of head-and-neck squamous-cell carcinoma (HNSCC) involves inactivation of at least one and possibly several tumor-suppressor genes on the long arm of chromosome 13. The fact that neither Rb1 nor BRCA2 appears to be inactivated in the majority of head-and-neck cancers suggests that novel tumor-suppressor genes are involved. We have used microsatellite repeat polymorphisms and PCR to detect several distinct minimal regions of deletion on 13q in supraglottic and oral squamous-cell carcinomas. One region maps to 13q34, the second to 13q14.3 and a potential third region, not reported in previous studies, maps to 13q12.1. Overall, 69% of the 145 tumors examined demonstrated allelic loss at one or more loci on 13q. We investigated whether a novel suppressor candidate mapping to 13q14. 3-q21, leukemia-associated gene 1, might also be involved in the progression of squamous-cell carcinomas. Multiplexed PCR revealed homozygous deletion of leu1 in one oral cavity tumor. This suggests that this gene or one nearby may be the actual target of deletions in this region of the chromosome arm.

Sanchez-Cespedes M, Okami K, Cairns P, Sidransky D
Molecular analysis of the candidate tumor suppressor gene ING1 in human head and neck tumors with 13q deletions.
Genes Chromosomes Cancer. 2000; 27(3):319-22 [PubMed] Related Publications
The candidate tumor-suppressor gene ING1 encodes p33(ING1), a nuclear protein which physically interacts with TP53. It has been shown that p33(ING1) acts in the same biochemical pathway as TP53, leading to cell growth inhibition. Interestingly, a rearrangement of the ING1 gene was found in a neuroblastoma cell line, supporting its involvement in tumor development. Because ING1 resides on the long arm of chromosome 13 (13q34) (a region frequently deleted in many tumor types), we sought to characterize its role in head and neck squamous-cell carcinoma (HNSCC). We first analyzed 44 primary tumors for loss of heterozygosity (LOH) at 13q, using four widely spaced microsatellite markers (13q14, 13q14.3-q22, 13q22, and 13q34). Twenty (48%) of the tumor samples showed LOH in all of the informative markers tested, including D13S1315 at 13q34. Two of the tumors displayed partial losses restricted to one marker (D13S118 at 13q14 in tumor 1164, and D13S135 at 13q14.3-q22 in tumor 1398). We then determined the genomic structure of the ING1 gene and sequenced the entire coding region in 20 primary tumors showing 13q LOH and in five head and neck cancer cell lines. A single germline polymorphism was detected in 10 of the tumors analyzed (T to C change) located 110 nucleotides upstream of the starting methionine. No somatic mutations were found in any of the samples, suggesting that ING1 is not a tumor suppressor gene target in head and neck cancer. Genes Chromosomes Cancer 27:319-322, 2000.

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