Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance

Abstract

BackgroundOvarian cancer (OC) is one of the most common types of gynecologic tumor over the world. The Glutathione S-transferase Mu (GSTM) has five members, including GSTM1-5. These GSTMs is involved in cell metabolism and detoxification, but their role in OC remains unknown.MethodsData from multiple public databases associated with OC and GSTMs were collected. Expression, prognosis, function enrichment, immune infiltration, stemness index, and drug sensitivity analysis was utilized to identify the roles of GSTMs in OC progression. RT-qPCR analysis confirmed the effect of AICAR, AT-7519, PHA-793887 and PI-103 on the mRNA levels of GSTM3/4.ResultsGSTM1-5 were decreased in OC samples compared to normal ovary samples. GSTM1/5 were positively correlated with OC prognosis, but GSTM3 was negatively correlated with OC prognosis. Function enrichment analysis indicated GSTMs were involved in glutathione metabolism, drug metabolism, and drug resistance. Immune infiltration analysis indicated GSTM2/3/4 promoted immune escape in OC. GSTM5 was significantly correlated with OC stemness index. GSTM3/4 were remarkedly associated with OC chemoresistance, especially in AICAR, AT-7519, PHA-793887 and PI-103.ConclusionGSTM3 was negatively correlated with OC prognosis, and associated with OC chemoresistance and immune escape. This gene may serve as potential prognostic biomarkers and therapeutic target for OC patients.

Multi-database analysis showed that genes associated with inflammatory response are important for prognosis prediction of renal clear cell carcinoma

“…[21] Similarly, a large number of studies have found that GSTM3 plays an important role in glioma, pancreatic cancer, and esophageal cancer. [22][23][24][25] This also con rms the value of this study. HPGD undertakes a wide range of functions in the body, and the proteins it encodes are distributed throughout the body.…”

Immunological Aspects of Cancer Cell Metabolism

“…Database analysis of ovarian cancer cells identified that the high expression of GSTM2, -3, and -4 correlates with the decreased expression of immune checkpoint molecules, such as CTLA-4 and TIGIT. Thus, the results highlighted the expression of GSTM2, -3, and -4 in promoting immune escape in ovarian cancer [62]. In addition, GSTA3 was identified as one of the highest contributing GST is a family of phase II detoxification enzymes that protect cells from the attack of reactive electrophiles.…”

“…Moreover, there is a report that the high expression of GPx3 in alveolar type 2 (AT2) epithelial cells induced the production of IL-10 in the premetastatic niche. IL-10-producing GPx3 AT2 cells were found to increase Treg and decrease CD4+ T cell proliferation; conversely, the deletion of GPx3 in AT2 cells suppressed lung metastasis [62]. GPx is a selenium-containing antioxidant enzyme that protects cells by reducing hydrogen peroxide and lipid peroxide into water and lipid alcohols.…”

A precise prognostic signature in CTNNB1-mutant hepatocellular carcinoma: Prognosis prediction and precision treatment exploration

“…Besides, a phase I study published in 2011 investigated that PHA-793887 induces severe, dose-related hepatic toxicity [ 57 ]. However, some latest studies have revealed the effective role of PHA-793887 in against osteosarcoma [ 58 ], lung cancer [ 59 ], prostate cancer [ 60 ] and ovarian cancer [ 61 ]. Therefore, our findings provided new application of PHA-793887 in HCC and theoretical basis for promoting the clinical application of PHA-793887 in CTNNB1-mutant HCC.…”