Research IndicatorsGraph generated 01 September 2019 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex
Specific Cancers (6)
Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
Cancer Genome Anatomy Project, NCI
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: IL1RL1 (cancer-related)
Thammineni KL, Thakur GK, Kaur N, Banerjee BDSignificance of MMP-9 and VEGF-C expression in North Indian women with breast cancer diagnosis.
Mol Cell Biochem. 2019; 457(1-2):93-103 [PubMed
] Related Publications
Metastasis accounts for the majority of cancer-associated mortality and renders the targeted therapy fruitless in the patients of breast cancer. Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF-C) are thought to be involved in tumor progression and metastasis. The aim of this study was to investigate the expression of MMP-9 and VEGF-C at both mRNA and protein levels in breast cancer and to correlate with lymph node metastasis and other clinicopathological characteristics. Biopsy specimens (N = 100) of breast cancer & benign breast disease (N = 100) were investigated for the mRNA expression of MMP-9 and VEGF-C by Real-time PCR and Protein expression by Western blot. Elevated levels of MMP-9 (p < 0.001) and VEGF-C (p < 0.001) expression were detected in breast cancer with corresponding to benign breast disease. Additionally, we found significantly increased levels of MMP-9 and VEGF-C in node-positive group with respect to node-negative group. Moreover, the levels of MMP-9 were significantly increased in larger tumor size (T3/T4) (p < 0.05) as compared to smaller size (T1/T2), which suggests that MMP-9 plays an important role in the progression of breast cancer. VEGF-C expression was associated with the TNM stage of tumor (p < 0.05). Further, a significant positive correlation was established between the mRNA levels of these two genes (p < 0.001). However, we could not obtain any significant correlation between expression of these genes with other clinicopathological parameters like tumor grade, age, menopausal status, and receptor status like ER, PR, and Her2. This study suggests that the high expression of MMP-9 and VEGF-C could act as markers for the tumor presence in breast cancer. In addition, this study recommends that expression of MMP-9 and VEGF-C was significantly associated with lymph node status and may provide valuable diagnosis of lymph node metastasis in breast cancer patients. Further, MMP-9 expression was associated with the tumor size and VEGF-C expression was correlated with the staging of the tumor, although no association was observed with other clinicopathological variables.
Moghimi M, Sobhan MR, Jarahzadeh MH, et al.Association of GSTM1, GSTT1, GSTM3, and GSTP1 Genes Polymorphisms with Susceptibility to Osteosarcoma: a Case- Control Study and Meta-Analysis
Asian Pac J Cancer Prev. 2019; 20(3):675-682 [PubMed
] Related Publications
Background: Some studies have investigated the association of GSTM1, GSTT1, GSTM3, and GSTP1
polymorphisms with susceptibility to osteosarcoma; however, these studies results are inconsistent and inconclusive. In
order to drive a more precise estimation, the present case-control study and meta-analysis was performed to investigate
association of GSTM1, GSTT1, GSTM3, and GSTP1 polymorphisms with osteosarcoma. Methods: Eligible articles
were identified by a search of several electronic databases for the period up to May 5, 2018. Odds ratios were pooled
using either fixed-effects or random effects models. Results: Finally, a total of 24 case-control studies with 2,405
osteosarcoma cases and 3,293 controls were included in the present meta-analysis. Overall, significantly increased
osteosarcoma risk was found when all studies were pooled into the meta-analysis of GSTT1 (Null vs. Present: OR= 1.247
95% CI 1.020-1.524, P= 0.031) and GSTP1 polymorphism (B vs. A: OR= 8.899 95% CI 2.722-29.094, P≤0.001). In
the stratified, significantly increased osteosarcoma risk was observed for GSTT1 polymorphism among Asians (Null
vs. Present: OR= 1.300 95% CI 1.034-1.635, P= 0.025), but not among Caucasians. Conclusions: This meta-analysis
demonstrated that GSTP1 and GSTT1 null genotype are associated with the risk of osteosarcoma. Future large welldesigned
epidemiological studies are warranted to validate our results.
Kalacas NA, Garcia JA, Sy Ortin T, et al.GSTM1 and GSTT1 Genetic Polymorphisms and Breast Cancer Risk in Selected Filipino Cases
Asian Pac J Cancer Prev. 2019; 20(2):529-535 [PubMed
] Related Publications
Background: The association of genetic polymorphisms with cancer development has been shown to be race- and
tumor site-specific. Thus, this study aimed to determine whether polymorphisms in the GSTM1 and GSTT1 genes
are associated with breast cancer among selected Filipinos. Methods: A total of 136 histologically confirmed breast
cancer cases were age- and sex-matched with 136 clinically healthy controls. Genomic DNA extracted from blood
samples of participants were screened for GSTM1 and GSTT1 genetic polymorphisms by multiplex PCR. Results:
The frequency of null genotypes among the cases (GSTM1: n=78; 57.4%; GSTT1: n=61; 44.9%) was not significantly
different (p>0.05) from the controls (GSTM1: n=93; 68.4%; GSTT1: n=59; 43.4%). It was also demonstrated that risk
for breast cancer was increased in passive smokers carrying the GSTM1 null (OR=2.56; 95% CI=1.38-4.75) or GSTT1
positive (OR=2.00; 95% CI=1.05-3.83) genotypes. Moreover, risk was decreased in alcohol users carrying the GSTT1
null (OR=0.39; 95% CI=0.16-0.97) genotype. Conclusion: This study suggests that variants of GSTM1 and GSTT1
may not be risk factors for breast cancer development among Filipinos. However, the risk may be increased when these
genotypes were combined with lifestyle or environmental factors.
Izumi D, Gao F, Toden S, et al.A genomewide transcriptomic approach identifies a novel gene expression signature for the detection of lymph node metastasis in patients with early stage gastric cancer.
EBioMedicine. 2019; 41:268-275 [PubMed
] Free Access to Full Article Related Publications
BACKGROUND: Although identification of lymph node (LN) metastasis is a well-recognized strategy for improving outcomes in patients with gastric cancer (GC), currently there is lack of availability of adequate molecular biomarkers that can identify such metastasis. Herein we have developed a robust gene-expression signature for detecting LN metastasis in early stage GC by using a transcriptome-wide biomarker discovery and subsequent validation in multiple clinical cohorts.
METHODS: A total of 532 patients with pathological T1 and T2 GC from 4 different cohorts were analyzed. Two independent datasets (n = 96, and n = 188) were used to establish a gene signature for the identification of LN metastasis in GC patients. The diagnostic performance of our gene-expression signature was subsequently assessed in two independent clinical cohorts using qRT-PCR assays (n = 101, and n = 147), and subsequently compared against conventional tumor markers and image-based diagnostics.
FINDINGS: We established a 15-gene signature by analyzing multiple high throughput datasets, which robustly distinguished LN status in both training (AUC = 0.765, 95% CI 0.667-0.863) and validation cohorts (AUC = 0.742, 95% CI 0.630-0.852). Notably, the 15-gene signature was significantly superior compared to the conventional tumor markers, CEA (P = .04) and CA19-9 (P = .005), as well as computed tomography-based imaging (P = .04).
INTERPRETATION: We have established and validated a 15-gene signature for detecting LN metastasis in GC patients, which offers a robust diagnostic tool for potentially improving treatment outcomes in gastric cancer patients. FUND: NIH: CA72851, CA181572, CA14792, CA202797, CA187956; CPRIT: RP140784: Baylor Sammons Cancer Center polot grants (AG), VPRT: 9610337, CityU 21101115, 11102317, 11103718; JCYJ20170307091256048 (XW).
Maccormick TM, Carvalho CES, Bravo Neto GP, Carvalho MDGDCComparative analysis of glutathione transferase genetic polymorphism, Helicobacter pylori and Epstein-Barr virus between the tumor area and the proximal and distal resection margins of gastric cancer.
Rev Col Bras Cir. 2019; 46(1):e2068 [PubMed
] Related Publications
OBJECTIVE: to compare the polymorphism of the Glutathione S-transferase theta 1 (GSTT1) and Glutathione S-transferase mu 1 (GSTM1) genes from the tumor area with the proximal and distal margins of stomach specimens resected from patients with gastric cancer, and to investigate the presence of Epstein-Barr virus (EBV) DNA and Helicobacter pylori.
METHODS: we prospectively collected tissue specimens from the tumor area and from the proximal and distal resection margins of the stomachs of ten patients with gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy, and submitted these specimens to DNA extraction. We compared the tumor area with the proximal and distal margins of the resected stomachs for polymorphism of GSTT1 and GSTM1 genes and investigated the presence of EBV-DNA and H. pylori. We used the p53 exon 5 gene as an internal control of the multiplex PCR reaction.
RESULTS: in one patient, we detected null GSTT1 and GSTM1 genotypes in the tumor area, in contrast to the presence of both genes in the proximal and distal margins. We found EBV-DNA and H. pylori in the tumor area and also in the proximal and distal margins. In another patient, the proximal margin was negative for GSTT1, and EBV-DNA was negative in the distal margin. In three patients, EBV-DNA was negative only in the distal margin.
CONCLUSION: this is the first report where different genotypes, EBV-DNA and H. pylori infection were observed in the same patient, indicating a probable deletion of these genes in response to tumor progression and intratumoral heterogeneity.
Vetto JT, Hsueh EC, Gastman BR, et al.Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.
Future Oncol. 2019; 15(11):1207-1217 [PubMed
] Related Publications
AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity?
PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively.
RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors.
CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy.
Cheng H, Huang C, Tang G, et al.Emerging role of EPHX1 in chemoresistance of acute myeloid leukemia by regurlating drug-metabolizing enzymes and apoptotic signaling.
Mol Carcinog. 2019; 58(5):808-819 [PubMed
] Related Publications
Microsomal epoxide hyrolase 1 (EPHX1) is a critical biotransformation enzyme and participants in both the detoxification and activation of potentially genotoxic epoxides. In this study, we firstly aimed to investigate the role of EPHX1 in the chemoresistance of acute myeloid leukemic cells to aclarubicin (ACM) and mitoxantrone (MIT). EPHX1 mRNA expression and prognosis were measured in acute myeloid leukemia (AML) patients, and the function of EPHX1 in leukemic cell viability and apoptosis induced by ACM and MIT was also measured. Our results found that EPHX1 expression is obviously associated with recurrence rate, overall survival and time of obtaining first complete remission in AML patients. EPHX1 silencing promoted ACM and MIT induced decrease in cell viability and cell apoptosis of HL-60, K562, and THP-1 that was inhibited by EPHX1 overexpression. EPHX1 reduced the susceptibility of leukemic cells to ACM and MIT by regulating drug-metabolizing enzymes (CYP1A1, GSTM1, and GSTT1) and apoptotic signaling (Bax, Bcl-2, Caspase-3, Caspase-9, and PARP1). Moreover, Nrf2 overexpression significantly increased EPHX1 expression and leukemic cell viability and decreased leukemic cell apoptosis. Taken together, we summarized the recent findings about the chemoresistance-promoting role of EPHX1, and the potential of targeting EPHX1 was proposed to counteract drug resistance in leukemia treatment.
Renal carcinoma cells express Membrane Type 1-Matrix Metalloproteinase (MT1-MMP, MMP-14) to degrade extracellular matrix components and a range of bioactive molecules to allow metastasis and cell proliferation. The activity of MT1-MMP is modulated by the endogenous inhibitors, Tissue Inhibitor of Metalloproteinases (TIMPs). In this study, we describe a novel strategy that would enable a "designer" TIMP-1 tailored specifically for MT1-MMP inhibition (V4A/P6V/T98L;
We observed inconsistent conclusions regarding the genetic role of glutathione S-transferase gene polymorphisms, including glutathione S-transferase M1 (
Xue F, Liu Z, Xu J, et al.Neferine inhibits growth and migration of gastrointestinal stromal tumor cell line GIST-T1 by up-regulation of miR-449a.
Biomed Pharmacother. 2019; 109:1951-1959 [PubMed
] Related Publications
BACKGROUND: Gastrointestinal stromal tumor (GIST) threatens the health of middle-aged and older people with high recurrence rate and low survival rate. In this study, Neferin (Nef) was hoped to control growth and migration of GIST cell line GIST-T1.
METHODS: Cell viability, proliferation, apoptosis, and migration were determined by cell counting kit-8 (CCK-8) assay, bromodeoxyuridine (BrdU) assay, Annexin V-FITC/PI double staining method, and Transwell assay, respectively. The expression level of miR-449a was determined by qRT-PCR. Cell transfection was conducted to alter the expression level of miR-449a. Protein expression levels of key factors involved in cell cycle, cell apoptosis, cell migration, PI3K/AKT pathway and Notch pathways were analyzed by western boltting.
RESULTS: Nef significantly inhibited GIST-T1 cell viability, proliferation, migration, but promoted cell apoptosis. The expression level of miR-449a was up-regulated in GIST-T1 cells after Nef treatment. Suppression of miR-449a reversed the Nef-induced GIST-T1 cell proliferation and migration inhibition, as well as cell apoptosis. Importantly, Nef inactivated PI3K/AKT and Notch pathways in GIST-T1 cells by up-regulating miR-449a. Inhibitors of PI3K/AKT and Notch pathways notably reversed the effects of Nef + miR-449a inhibitor on GIST-T1 cell proliferation, apoptosis and migration. Besides, Nef also suppressed human gastric cancer SGC7901 cell migration and induced cell apoptosis.
CONCLUSION: Nef suppressed growth and migration of GIST-T1 cells possibly via up-regulation of miR-449a and then inactivation of PI3K/AKT and Notch pathways.
Dong Z, Huang K, Liao B, et al.Prediction of sorafenib treatment-related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation.
Eur Radiol. 2019; 29(5):2272-2282 [PubMed
] Related Publications
PURPOSE: To investigate the feasibility of prediction for targeted therapy-related gene expression in hepatocellular carcinoma (HCC) using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI).
MATERIALS AND METHODS: Ninety-one patients (81 men, mean age 53.9 ± 12 years) with solitary HCC who underwent preoperative enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, intratumoral vessels, peritumor enhancement, peritumor hypointensity, signal intensity ratio on DWI, T1 relaxation times, and the reduction rate between pre- and post-contrast enhancement images were assessed. The operation and histopathological evaluation were performed within 2 weeks after MRI examination (mean time 7 days). The expression levels of BRAF, RAF1, VEGFR2, and VEGFR3 were evaluated. The associations between these imaging features and gene expression levels were investigated.
RESULTS: Tumor incomplete capsules or non-capsules (p = 0.001) and intratumoral vessels (p = 0.002) were significantly associated with BRAF expression, and tumor incomplete capsules or non-capsules (p = 0.001) and intratumoral vessels (p = 0.013) with RAF1 expression. There was no significant association between the expression of VEGFR2, VEGFR3, and all examined MRI features. Multivariate logistic regression showed that incomplete tumor capsule (p = 0.002) and non-capsule (p = 0.004) were independent risk factors of HCC with high BRAF expression; incomplete tumor capsule (p < 0.001) and non-capsule (p = 0.040) were independent risk factors of HCC with high RAF1 expression.
CONCLUSION: The presence of incomplete capsule or intratumoral vessels and the absence of capsule are potential indicators of high BRAF and RAF1 expression. Gadoxetic acid-enhanced MRI may facilitate the choice of gene therapy for patients with HCC.
KEY POINTS: • Incomplete tumor capsule and non-capsule were independent risk factors of HCC with high BRAF and RAF1 expression. • The presence of intratumoral vessels was a potential indicator of high BRAF and RAF1 expression. • Gadoxetic acid-enhanced MRI may be a predictor of efficacy of treatment with sorafenib.
BACKGROUND: The Oncotype DX
METHODS: The National Cancer Database was used to identify all patients with T1-T3, ER-positive, HER2-negative primary invasive breast cancer diagnosed from 2010 to 2015 who had Oncotype DX recurrence scores (RS) and received NCT. RS were classified as low, intermediate, or high. Unadjusted and adjusted regression analyses were performed to determine the association between pathologic complete response (pCR) and RS.
RESULTS: A total of 989 patients (mean age, 54.6 years) with available RS who underwent NCT were identified. RS were low in 227 (23.0%) patients, intermediate in 450 (45.5%) patients, and high in 312 (31.5%) patients. Most patients had a T1 (431 [43.6%]) or T2 tumor (451 [45.6%]). Most had N0 disease (757 [76.5%]). Tumor grades were 1 (123 [12.4%]), 2 (517 [52.3%]), or 3 (349 [35.3%]). pCR was achieved by 42 (4.3%) patients. Adjusted multivariable analysis showed a significant association between pCR and high RS (odds ratio 4.87; 95% confidence interval 2.01-11.82).
CONCLUSIONS: High Oncotype DX RS was associated with pCR after NCT in this national cohort of ER-positive, HER2-negative patients. Oncotype DX testing could help to identify patients most suited for NCT and should be considered for incorporation into the multidisciplinary decision-making process.
Ling T, Yu F, Cao HmiR-182 controls cell growth in gastrointestinal stromal tumors by negatively regulating CYLD expression.
Oncol Rep. 2018; 40(6):3705-3713 [PubMed
] Related Publications
Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor of the digestive tract. MicroRNAs (miRNAs) are short non-coding RNAs, which control gene expression at a post-transcriptional level. Dysregulated miRNAs are involved in various types of human disease, including cancer. In the present study, it was revealed that miRNA-182 (miR-182) expression was significantly upregulated in human GISTs compared with adjacent normal tissues. Overexpression of miR-182 enhanced GIST-T1 cell growth, with increased proliferation and decreased apoptosis. miR-182 upregulation also promoted colony formation and migration of GIST-T1 cells. In addition, cylindromatosis (CYLD) was identified as a direct target of miR-182. Overexpression of miR-182 suppressed CYLD expression and enhanced downstream nuclear factor (NF)-κB activation. It was also determined that the expression of CYLD was downregulated in association with upregulated miR-182 in human GISTs. In conclusion, these results demonstrated that miR-182 promoted GIST cell growth by negatively regulating CYLD expression. These findings indicated that miR-182 antagonist may be a promising therapeutic strategy for the treatment of human GIST.
Kakurina GV, Kondakova IV, Spirina LV, et al.Expression of Genes Encoding Cell Motility Proteins during Progression of Head and Neck Squamous Cell Carcinoma.
Bull Exp Biol Med. 2018; 166(2):250-252 [PubMed
] Related Publications
The model of head and neck squamous cell carcinoma (HNSCC) was used to study the expression of genes encoding actin-binding proteins depending on the type of cell motility. The expression of SNAIL1 and CAPN2 mRNA in HNSCC tissue was higher than in specimens of dysplastic epithelium of the larynx and hypopharynx, which can be explained by activation of mesenchymal and amoeboid types of cell motility. In biopsy material of HNSCC patients with T1-2N0M0, expression of genes responsible for actin-binding proteins differed from that of patients with pretumor pathology of the larynx and hypopharynx: expression of FSCN was lower, while expressions of EZR and CAP1 were higher. The data attest that progression of HNSCC is associated with activation of both types of cell motility and with the changes in the expression of mRNA encoding cell motility proteins.
Spake CSL, Reid DBC, Daniels AHRapid Progression of Metastatic Panspinal Epidural Non-Small Cell Lung Cancer After Discontinuation of Alectinib.
World Neurosurg. 2019; 122:590-592 [PubMed
] Related Publications
BACKGROUND: Rapid progression of metastatic non-small cell lung cancer (NSCLC) after discontinuation of tyrosine kinase inhibitors or anaplastic lymphoma kinase (ALK) inhibitors has been described and is associated with a poor prognosis. We describe the first reported case of accelerated NSCLC tumor extension throughout the entire spinal epidural space.
CASE DESCRIPTION: A 68-year-old woman with stage IV ALK-positive metastatic NSCLC presented with acute neck pain, urinary retention, and lower extremity weakness 15 days post discontinuation of alectinib. Magnetic resonance imaging (MRI) with contrast was significant for a new compressive lesion spanning the entire cervical, thoracic, and lumbar spine, which was new compared with MRI obtained 20 days before and was suspicious for infection. Cervical (C3-C7), thoracic (T9-T12), and lumbar (L3-L5) decompression were performed with collection of culture and pathology specimens. Repeat MRI obtained for acute neurologic deterioration on postoperative day 2 noted further progression of disease and continued thoracic cord compression. After urgent T1-9 laminectomy, specimens were again sent for pathology, cultures, and cytology. No evidence of infection was noted, and all pathologic specimens evaluated were consistent with metastatic adenocarcinoma. Despite operative intervention, the patient continued to decline, suffering from recurrent pleural effusions, and eventual cardiopulmonary arrest 11 days after admission.
CONCLUSIONS: The differential diagnosis when evaluating presumed spine epidural abscess should include tumor and metastatic disease, even in cases of rapid development. Recent termination of tyrosine kinase inhibitors or ALK inhibitors may result in severe disease flares, and a history of such should raise clinical suspicion for metastatic progression. In addition to cultures, biopsy for pathologic diagnosis should be collected during decompressive surgery.
Wang M, Wu K, Zhang P, et al.The Prognostic Significance of the Oncotype DX Recurrence Score in T
Ann Surg Oncol. 2019; 26(5):1227-1235 [PubMed
] Related Publications
BACKGROUND: This study aimed to evaluate the prognostic significance of the Oncotype DX recurrence score (RS) in T
METHODS: The Surveillance, Epidemiology, and End Results database was searched to identify ER-positive invasive ductal breast cancer in T
RESULTS: The study enrolled 4059 cases categorized into prognostic stages IA to IIB. The RS risk groups were positively correlated with pathological prognostic stages (P < 0.001). The RS risk groups differed significantly in terms of BCSS and OS (P < 0.001). According to the multivariate analysis, RS risk group was an independent prognostic factor for BCSS and OS together with the pathological prognostic stage. The subgroup analysis showed similar survival rates across pathological prognostic stages in the RS low-risk group but significant differences in survival rates among pathological prognostic stages in the RS intermediate-risk group. The survival rates among the RS risk groups also differed significantly in pathological prognostic stage IA.
CONCLUSIONS: Oncotype DX RS provided independent prognostic significance to complement the prognostic staging system.
OBJECTIVE: To study the effects of single-nucleotide polymorphisms of the
METHODS: A total of 225 Chinese Han nationality patients undergoing thoracoscopic-assisted radical resection of lung cancer were enrolled in the present study. Among them, 132 were males (58.67%) and 93 (41.33%) were females having American Society of Anesthesiologists statuses classified as grades I or II. The rs1799971, rs563649 and rs1323040 genotypes of the
RESULTS: The sufentanil doses at T1, T2 and T3 were significantly higher in radical-operation lung cancer patients with mutant homozygous rs1799971 and rs1323040 loci in the
CONCLUSION: The rs1799971 and rs1323040 polymorphisms of the
Chernaya G, Mikhno N, Khabalova T, et al.The expression profile of integrin receptors and osteopontin in thyroid malignancies varies depending on the tumor progression rate and presence of BRAF V600E mutation.
Surg Oncol. 2018; 27(4):702-708 [PubMed
] Related Publications
Thyroid cancer (TC) is one of the most common malignancy of the human endocrine system. BRAF V600E mutation is the most frequent genetic alteration of papillary carcinoma, the most frequent TC, which effects RAS-RAF-MEK intracellular signaling pathway. These alterations in RAS-RAF-MEK pathway lead to changes in expression levels of cell membrane integrin receptors and their ligand - extracellular matrix protein osteopontin, which in turn increases the metastatic potential of tumor cells. Thus, integrins and their ligand osteopontin can be considered as potential biomarkers of tumor progression and aggressive tumor phenotypes. The aim of the study was to evaluate the expression levels of integrin receptors ITGA2, ITGA3, ITGAV, ITGA6, ITGA9, ITGB1, ITGB3 and their ligands OPNa, OPNb in the thyroid cancer with different BRAF V600E mutation status.
METHODS: Thyroid tumor samples of 70 patients obtained during surgical treatment were analyzed. Expression levels of the investigated genes were evaluated by real time RT-PCR. Fluorescent immunohistochemistry (IHC) was used to confirm the PCR results and to estimate the amount of protein levels. For IHC frozen sections were used. BRAF V600E mutation was determined using allele-specific amplification. Nonparametric criteria (Kruskal Wallis, Wilcoxon and Mann-Whitney tests) were used to evaluate group differences. P values of less than 0.05 were considered as statistically significant.
RESULTS: A higher gene expression level of ITGA2 (1.9-fold, p = 0.037), ITGA3 (21.1-fold, p = 0.041) and ITGA5 (2.08-fold, p = 0.048) was observed in papillary thyroid cancer (PTC) tissue in comparison with median expression level in control samples (conventionally normal tissue of thyroid gland). These changes were confirmed by IHC (significant changes for α2 integrin). ITGAV expression level was statistically significantly higher in follicular thyroid cancer (FTC) (2.0-fold, p = 0.040). Next, high gene expression levels in tissue samples of lymph node metastases were observed for ITGA5 (2.92-fold, p = 0.015), OPNb (4.36-fold, p = 0.037). For genes ITGA3 (37.48-fold, p = 0.017790), ITGA6 (18.76-fold, p = 0.028921) and ITGA9 (12.52-fold, p = 0.026710) higher expression level was detected in T
CONCLUSION: Identified changes in expression levels of the studied genes indicate that they could play an important role in tumor progression, and their expression could be affected by the product of mutant BRAF gene. Integrins and their ligand osteopontin might be considered as potential markers in determining prognosis and treatment of TC.
BACKGROUND: Prostate cancer is a common malignancy of the male genitourinary system that occurs worldwide. The current research aims to investigate caveolin-1 expression in prostate cancer tissue and its relationship with pathological grade, clinical pathologic staging, and preoperative prostate-specific antigen (PSA) levels.
METHODS: From January 2012 to December 2014, samples from 47 patients with prostate cancer who had received transurethral prostatic resection (TURP) and 20 patients with benign prostatic hyperplasia were collected at the First Affiliated Hospital of Guangxi Medical University. Caveolin-1 was detected by streptavidin-perosidase (SP) immunohistochemical staining in pathological tissue slices. The results were statistically analyzed for pathological grade, clinical stage, and preoperative PSA level.
RESULTS: The expression of caveolin-1 was significantly higher in prostate cancer samples than in benign prostatic hyperplasia samples (P < 0.05), and caveolin-1 expression was significantly different among the pathological grades of poorly, moderately and well-differentiated prostate cancer (P < 0.05). The difference in caveolin-1 expression was significant for different clinical stages (T1-T2 and T3-T4) of prostate cancer (P < 0.05). The difference in caveolin-1 expression was not significant among samples with different preoperative PSA levels (0-10, 10-100 and > 100 μg/L) (P > 0.05).
CONCLUSIONS: Caveolin-1 is closely related to the pathological grade and clinical stage of prostate cancer after transurethral surgery, and it may be a novel tumor marker for prostate cancer. The expression of caveolin-1 is not associated with preoperative serum PSA levels.
BACKGROUND: We conducted a meta-analysis to evaluate the relationship between the glutathione S-transferase μ1 (GSTM1)- and glutathione S-transferase θ1 (GSTT1)- null genotypes and susceptibility to bladder cancer.
METHODS: We identified association reports from the databases of PubMed, Embase, the Cochrane Library and the China Biological Medicine Database (CBM disc) on July 1, 2017 and synthesized eligible investigations. Results were expressed using odds ratios (ORs) for dichotomous data, and we also calculated 95% confidence intervals (CIs).
RESULTS: In this meta-analysis, we found that the GSTM1-null genotype was associated with bladder cancer risk in the overall population, and individually in whites, Africans and Asians (overall population: OR = 1.40, 95% CI: 1.31-1.48, P<0.00001; whites: OR = 1.39, 95% CI: 1.26-1.54, P<0.00001; Africans: OR = 1.54, 95% CI: 1.16-2.05, P = 0.003; Asians: OR = 1.45, 95% CI: 1.33-1.59, P<0.00001). The GSTT1-null genotype was associated with bladder cancer risk in the overall population, but not in whites, in Africans or Asians (overall population: OR = 1.11, 95% CI: 1.01-1.22, P = 0.03; whites: OR = 1.16, 95% CI: 0.99-1.36, P = 0.07; Africans: OR = 1.07, 95% CI: 0.65-1.76, P = 0.79; Asians: OR = 1.05, 95% CI: 0.91-1.22, P = 0.51). Interestingly, a dual-null GSTM1-GSTT1 genotype was associated with bladder cancer risk in the overall population and in Asians (overall population: OR = 1.48, 95% CI: 1.15-1.92, P = 0.002; Asians: OR = 1.62, 95% CI: 1.15-2.28, P = 0.006). In conclusion, the GSTM1-null, GSTT1-null and dual-null GSTM1-GSTT1 genotypes might be associated with the onset of bladder cancer, but additional genetic-epidemiological studies should be conducted to explore this association further.
Ishida Y, Tsuda M, Sawamura Y, et al."Integrated diagnosis" of pilocytic astrocytoma: Molecular diagnostic procedure for an unusual case.
Pathol Int. 2018; 68(12):694-699 [PubMed
] Related Publications
A 24 year-old female presented with a mass lesion in the right temporal lobe. This case was difficult to diagnose using histological and immunological methods and therefore molecular analyses were applied to provide a definitive diagnosis. The tumor was well-demarcated, partially cystic, and irregularly-enhanced on gadolinium-enhanced T1-weighted magnetic resonance images. Pathologically, a large part of the tumor consisted of cells with fine cytoplasmic processes on a myxoid and mucinous background. Cells formed a microcystic structure around the mucinous tissue. Numerous eosinophilic granular bodies, but not Rosenthal fibers, were present. The solid and compact regions of the tumor were composed of fasciculation of dense fibrous glial tissues and occasional multinucleated giant cells. Tumor cells and their fragmented cytoplasmic processes were positively stained with GFAP, while eosinophilic granular bodies were both positive and negative. Xanthomatous changes were not detected and the reticulin fibers were restricted to vascular tissues. The MIB1 index was scored as approximately 10%. In molecular analyses of BRAF, the KIAA1549-BRAF (K16-B9) fusion gene was detected in all tumor regions, whereas BRAF V600E mutation was not detected by either conventional Sanger sequencing or the Eprobe-PCR method. Based on the results of the molecular analyses, this case was diagnosed as pilocytic astrocytoma.
Adibhesami G, Shahsavari GR, Amiri A, et al.Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) Polymorphisms and Lung Cancer Risk among a Select Group of Iranian People
Asian Pac J Cancer Prev. 2018; 19(10):2921-2927 [PubMed
] Free Access to Full Article Related Publications
Objective(s): Lung cancer, caused primarily by smoking, is one of the leading determinants of mortality throughout
the world. Here we investigated the effects of polymorphisms in two enzymes, i.e., GSTT1 and GSTM1, related to
the antioxidant defense line against carcinogens associated with lung cancer among a select group of Iranian people.
Materials and Methods: One hundred and twenty lung cancer patients from two referral centers in Tehran, Iran, were
recruited for comparison with 120 healthy controls. Genomic DNA was extracted from the FFPE tumor tissues of
the select cases and peripheral blood buffy coats of healthy controls. The polymorphisms of GSTT1 and GSTM1 were
investigated by multiplex polymerase chain reaction. Results: With the 240 samples studied, no specific relationship
with lung cancer was discerned for the GSTM1 (P=0.35; OR=1/33; 95% CI=0.79-2.25) polymorphism, but the GSTT1
(P=0.005; OR=2.4; CI=1.32-4.35) gene polymorphism revealed a notable association on logistic regression, taking
into account age and sex factors. Furthermore, the GSTT1 genotype distribution in patients with LSCC was different
from that of healthy cases (P=0.006; OR=3.11; CI=1.38-7.04). The risk of developing lung cancer with the T0M1
genotype was 3.46 times higher than with T1M1 genotype (P=0.002; OR=3.46; CI=1.61-7.46). Moreover, the risk of
developing LSCC cancer in people with T0M1 genotypes was significantly elevated (P=0.004; OR=4.5; CI=1.62-12.52).
Conclusion: Unlike GSTM1, the GSTT1 genotype distribution is associated with the incidence of lung cancer in Iranian
people. Different types of lung cancer appear to show various correlations with GST polymorphisms in this regard.
Objective: Prostate cancer (PCa) is a major public health problem worldwide, with high morbidity and mortality
levels. Advanced age, androgen stimulation, and ethnicity have been reported to be possible risk factors. It has been
suggested that particular genetic polymorphisms in glutathione S-transferases (GST), xenobiotic-metabolising enzymes,
could predispose to prostate cancer through heritable deficiency in detoxification of environmental carcinogens.
Conflicts in the published results and the absence of similar in depth studies in Algeria prompted us to perform the
present case-control study of GSTM1 and GSTT1 polymorphisms and their possible association with PCa in an Algerian
population. Methods: We determined GSTM1 and GSTT1 genotypes for 49 histologically verified prostate cancer
patients and in 41 age-matched healthy controls by multiplex polymerase chain reaction (PCR) using peripheral blood
DNA samples. Result: While an association between the GSTM1 null genotype and PCa risk (OR= 3.69, 95% CI=
1.30-10.44; P = 0.01) was evident, the GSTT1 null genotype (OR= 0.92, 95% IC= 0.32-2.62; P = 0.49) appeared without
influence. Furthermore, no statistically significant differences between the double null genotype and PCa is detected,
also no statistically significant differences between smoking status and PCa is detected. Conclusion: The GSTM1 null
genotype may increase individual susceptibility to prostate cancer. On the other hand, the null-activity genotype of
GSTT1 did not appear to contribute to the risk of prostate cancer in our population.
AIM: To evaluate the association between polymorphisms in glutathione S transferases (GSTs) and the risk of sporadic colorectal cancer (SCRC), tumor progression and the survival of patients.
METHODS: A case-control study of 970 individuals from the Brazilian population was conducted (232 individuals from the case group with colorectal cancer and 738 individuals from the control group without a history of cancer). PCR multiplex and PCR-RFLP techniques were used to genotype the GST polymorphisms. The tumors were categorized according to the TNM classification: tumor extension (T), affected lymph nodes (N), and presence of metastasis (M). Logistic regression, multiple logistic regression and survival analysis were used to analyze the data. The results are presented in terms of odds ratio (OR) and 95% confidence interval (CI). The level of significance was set at 5% (
RESULTS: Age equal to or over 62 years (OR = 8.79; 95%CI: 5.90-13.09,
CONCLUSION: Females aged 62 years or older are more susceptible to SCRC. Polymorphisms of
BACKGROUND: MicroRNAs (miRNAs) are important regulators of cellular function and have been associated with both aging and cancer, but the impact of chemotherapy on age-related miRNAs has barely been studied. Our aim was to examine whether chemotherapy accelerates the aging process in elderly breast cancer patients using miRNA expression profiling.
METHODS: We monitored age-related miRNAs in blood of women, aged 70 or older, receiving adjuvant chemotherapy (docetaxel and cyclophosphamide, TC) for invasive breast cancer (chemo group, CTG, n = 46). A control group of older breast cancer patients without chemotherapy was included for comparison (control group, CG, n = 43). All patients underwent geriatric assessment at inclusion (T0), after 3 months (T1) and 1 year (T2). Moreover, we analysed the serum expression of nine age-related miRNAs (miR-20a, miR-30b, miR-34a, miR-106b, miR-191, miR-301a, miR-320b, miR-374a, miR-378a) at each timepoint.
RESULTS: Except for miR-106b, which behaved slightly different in CTG compared to CG, all miRNAs showed moderate fluctuations during the study course with no significant differences between groups. Several age-related miRNAs correlated with clinical frailty (miR-106b, miR-191, miR-301a, miR-320b, miR-374a), as well as with other biomarkers of aging, particularly Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1) (miR-106b, miR-301a, miR-374a-5p, miR-378a-3p). Moreover, based on their 'aging miRNA' profiles, patients clustered into two distinct groups exhibiting significantly different results for several biological/clinical aging parameters.
CONCLUSIONS: These results further corroborate our earlier report, stating that adjuvant TC chemotherapy does not significantly boost aging progression in elderly breast cancer patients. Our findings also endorsed specific age-related miRNAs as promising aging/frailty biomarkers in oncogeriatric populations.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT00849758 . Registered on 20 February 2009. This clinical trial was registered prospectively.
Wang H, Gao X, Zhang X, et al.Glutathione S-Transferase Gene Polymorphisms are Associated with an Improved Treatment Response to Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer (NSCLC): A Meta-Analysis.
Med Sci Monit. 2018; 24:7482-7492 [PubMed
] Free Access to Full Article Related Publications
BACKGROUND Previous studies have shown an association with glutathione S-transferase (GST) gene polymorphisms in patients with non-small cell lung cancer (NSCLC) and treatment response. This study aimed to undertake a literature review and meta-analysis of GST gene polymorphisms, including GSTT1, GSTM1, and GSTP1 IIe105Val, and the treatment response to cisplatin-based chemotherapy in patients with NSCLC. MATERIAL AND METHODS A literature search was undertaken of the main medical publication databases for publications, up to March 2017, on the association between GSTT1, GSTM1, and GSTP1 IIe105Val polymorphisms and the clinical outcome in patients with NSCLC treated with cisplatin-based chemotherapy. A random fixed-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (CI) to evaluate the associations, considering multiple genetic models. A subgroup analysis according to ethnicity was performed. RESULTS Twenty-three published studies were identified that showed that both the null GSTM1 and the GG genotype of GSTP1 IIe105Val were associated with improved treatment response to cisplatin-based chemotherapy (GSTT1 present/null: OR=1.328; 95% CI, 1.074-1.643) (GSTP1 GG + AG vs. AA: OR=0.596; 95% CI, 0.468-0.759). In subgroup analysis, the GSTP1 polymorphism was significantly associated with treatment response in East-Asian patients, but not in Caucasian patients. CONCLUSIONS Meta-analysis showed that the GG genotype of GSTP1 IIe105Val and the null GSTM1 genotype were associated with an improved treatment response to cisplatin-based chemotherapy in patients with NSCLC, especially in East-Asian patients.
Braczkowski RS, Kwiatkowski R, Danikiewicz A, et al.Vitamin D receptor gene polymorphisms and prostate cancer.
J Biol Regul Homeost Agents. 2018 Sep-Oct; 32(5):1245-1248 [PubMed
] Related Publications
Prostate cancer (PC) is the most common cancer among men worldwide and its pathogenesis is complex. The development of PC depends on family and environmental factors. Vitamin D can be associated with both of these factors. Its reduced serum concentration has been reported in a number of tumors. However, in the case of PC, the study results are conflicting. Polymorphism of VDR gene may also be involved in the development of this cancer. The aim of the study was to compare the frequency of selected polymorphisms in patients with PC and in men without this disease. Seventy-two Caucasian males aged 35-75 years with histologically proven PC (T1/T2) were enrolled in the study group. Seventy-two random age-matched Caucasian out-patient subjects formed the control group. VDR (FokI, BsmI and TaqI) gene polymorphism (rs2228570, rs1544410, rs731236) was determined by TaqMan® SNP Genotyping. The Hardy-Weinberg Equilibrium (HWE) - p> 0.05 was in all studied polymorphisms. Deviations from the HWE were not found. There were no differences between the study group and the control group. No difference was found when the groups were compared in terms of age or the Gleason score.
BACKGROUND: In the past 2 decades, metastasis-associated gene 1 (MTA1) has attracted attention for its close association with cancer progression and its roles in chromatin remodeling processes, making it a central gene in cancer. The present meta-analysis was performed to assess MTA1 expression in solid tumors.
MATERIALS AND METHODS: This analysis identified studies that evaluated the relationship between MTA1 expression and clinical characteristics or prognosis of patients with solid tumors via the PubMed, Cochrane Library, and Embase electronic databases. Fixed-effect and random-effect meta-analytical techniques were used to correlate MTA1 expression with outcome measures. The outcome variables are shown as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI).
RESULTS: Analysis of 40 cohort studies involving 4564 cancer patients revealed a significant association of MTA1 overexpression with tumor patient age (>50 vs. <50 years: combined OR 0.73, 95% CI 0.57-0.94), tumor grade (G3/4 vs. G1/2: combined OR 1.94, 95% CI 1.48-2.53), tumor size (>3 cm vs. <3 cm: combined OR 2.35, 95% CI 1.73-3.19), T stage (T3/4 vs. T1/2: combined OR 2.11, 95% CI 1.74-2.56), lymph node metastasis (yes vs. no: combined OR 2.92, 95% CI 2.26-3.75), distant metastasis (yes vs. no: combined OR 2.26, 95% CI 1.42-3.59), TNM stage (III/IV vs. I/II: combined OR 2.50, 95% CI 1.84-3.38), vascular invasion (yes vs. no: combined OR 2.26, 95% CI 1.92-3.56), and poor overall survival time (HR 1.83; 95% CI: 1.53-2.20; P = .000).
CONCLUSIONS: Our analyses demonstrate that MTA1 was an effective predictor of a worse prognosis in tumor patients. Moreover, MTA1 may play important role in tumor progression and outcome, and targeting MTA1 may be a new strategy for anti-cancer therapy.
Chin-Lenn L, De Boer RH, Segelov E, et al.The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.
Asia Pac J Clin Oncol. 2018; 14(6):410-416 [PubMed
] Related Publications
OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs.
METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought.
RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%.
CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.
BACKGROUND: Aldo-keto reductases (AKRs) modify carbonyl groups on aldehyde or ketones to form primary or secondary alcohols, which are then conjugated with sulfates or glucuronide for excretion. The AKR1B10 gene encodes a member of the AKR superfamily. Overexpression of AKR1B10 plays an important role in the tumorigenesis of lung cancer cells; however, the prognostic value of AKR1B10 expression in patients with lung adenocarcinoma has not been well demonstrated.
METHODS: A total of 96 patients with resected lung adenocarcinoma were included in the study. AKR1B10 expression was determined by immunohistochemistry in tumor specimens. The prognostic value of AKR1B10 overexpression and its relationship with clinicopathological variables were investigated.
RESULTS: AKR1B10 overexpression was identified in 22 (22.9%) of the 96 patients and tended to be significantly associated with N1 or N2 status (P = 0.055). AKR1B10 overexpression was not a significant prognostic factor for overall survival (P = 0.301) but was a significant prognostic factor for poor recurrence-free survival (P = 0.015). T status (T3 or T4 vs. T1 or T2; P = 0.020), N1 or N2 (vs. N0; P = 0.019), predominant pattern group (lepidic/acinar/papillary vs. micropapillary/solid; P = 0.023), and AKR1B10 overexpression (P = 0.013) were significant prognostic factors for poor recurrence-free survival in multivariate analysis.
CONCLUSIONS: AKR1B10 overexpression was a significant prognostic factor for poor recurrence-free survival in patients with resected lung adenocarcinoma. This information is useful to stratify patients at high-risk of recurrence after lung adenocarcinoma resection.