The prognostic impact of GSTM1/GSTP1 genetic variants in bladder Cancer

Abstract

BackgroundThe glutathione S-transferases (GSTs) are a superfamily of phase II detoxifying enzymes that inactivates a wide variety of potential carcinogens through glutathione conjugation. Polymorphic changes in the GST genes have been reported to be associated with increased susceptibility to cancer development and anticancer drug resistance. In this study, we investigated the association between genetic variants in GSTM1 and GSTP1 and patients’ clinicopathological parameters. The prognostic values of such associations were evaluated among bladder cancer patients.MethodsGenotyping of GSTM1 and GSTP1 in bladder cancer patients was assessed using polymerase chain reaction followed by DNA sequencing. Overall survival was estimated using the Kaplan-Meier method and multiple logistic regression and correlation analysis were performed.ResultsThe GSTM1 null genotype was significantly associated with poor overall survival compared with the wild-type GSTM1 genotype. There was a trend towards better overall survival in patients with wild-type GSTP1 allele (AA) compared with GSTP1 (AG/GG) genotype. Interestingly, Kaplan-meier survival curve for GSTM1 null patients adjusted for sub-cohort with amplified HER2 gene showed poor survival compared with the GSTM1 null/ non-amplified HER2 gene. Also the same population when adjusted with HER2 protein expression, data showed poor survival for patients harboring GSTM1 null/high HER2 protein expression compared with low protein expression.ConclusionThis study focuses on the impact of GSTM1 null genotype on bladder cancer patients’ outcome. Further investigations are required to delineate the underlying mechanisms of combined GSTM−/− and HER2 status in bladder cancer.

Ligandability Assessment of Human Glutathione Transferase M1-1 Using Pesticides as Chemical Probes

“…It is well-known that certain GSTs classes, namely a, μ and π, are involved in the development of anti-cancer drug-resistance phenomena [ 11 ]. For example, GSTA1-1 and GSTP1-1 were reported to be, in short, connected with an increased risk of gastric, breast and pancreatic cancer [ 1 , 12 , 13 , 14 , 15 , 16 ]. Moreover, the isoenzyme GSTM1-1 is mostly studied in humans for its correlation with many types of cancer [ 13 , 14 , 15 ], while other studies support its pertinence with Parkinson’s disease [ 17 , 18 ].…”

“…For example, GSTA1-1 and GSTP1-1 were reported to be, in short, connected with an increased risk of gastric, breast and pancreatic cancer [ 1 , 12 , 13 , 14 , 15 , 16 ]. Moreover, the isoenzyme GSTM1-1 is mostly studied in humans for its correlation with many types of cancer [ 13 , 14 , 15 ], while other studies support its pertinence with Parkinson’s disease [ 17 , 18 ]. Many studies have shown that an overexpression of GSTM1-1 may have direct impact on chemoresistance [ 13 , 19 ].…”

<p>Phosphorylated MAPK14 Promotes the Proliferation and Migration of Bladder Cancer Cells by Maintaining RUNX2 Protein Abundance</p>

“…Bladder cancer, the ninth most common cancer worldwide, is a highly heterogeneous disease and an important cause of cancer metastasis-related death. 1 In the United States, it has been estimated that there would be about 80,470 new bladder cancer cases and 17,670 deaths in 2019. 2 The incidence of bladder cancer is higher in males and 70% of patients with bladder cancer are initially diagnosed as non-muscular invasive diseases.…”

“…There are several risk factors related to bladder cancer, such as smoking, aging and exposure to the products of chemical industries. 1 , 3 In recent years, despite the progress in clinical diagnosis and treatment of bladder cancer, it remains to be a perplexing problem in clinical management due to its high metastasis rate. 4 Therefore, a comprehensive understanding of the pathogenetic mechanism of bladder cancer would improve the prognosis of patients.…”

Prognostic and predictive value of a mRNA signature in peripheral T‐cell lymphomas: A mRNA expression analysis

“…It has also been demonstrated that DOCK2 was abnormally elevated expressed in B-cell lymphoma and the overexpressed DOCK2 correlated with the reduced prognosis of chronic lymphocytic leukaemia 40,41. GSTM1 (glutathione S-transferase M1) is a member of the family of cytosolic GSTs, and the null genotype of GSTM1 has been proven to be associated with risk of colorectal cancer, renal cell carcinoma, oesophageal cancer, nasopharyngeal cancer and bladder cancer [42][43][44][45][46]. LAPTM5 (lysosomal-associated protein transmembrane 5) is a membrane protein that can inhibit the expression of T-cell receptor (TCR) and play a positive role in migration and invasion of ovarian cancer cell but play a negative regulator of T-cell or B-cell receptor downstream signalling.…”