Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma
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RESEARCH ARTICLE
Open Access
Clinical significance and biological mechanisms of glutathione S-transferase mu gene family in colon adenocarcinoma Erna Guo1,2* , Haotang Wei3, Xiwen Liao4, Liuyu Wu1 and Xiaoyun Zeng1*
Abstract Background: Colon adenocarcinoma (COAD) is the most common form of colon cancer. The glutathione Stransferase Mu (GSTM) gene belongs to the GST gene family, which functions in cell metabolism and detoxification. The relationship between GSTM and COAD and the underlying mechanism remain unknown. Methods: Data extracted from The Cancer Genome Atlas included mRNA expression and clinical information such as gender, age, and tumor stage. Prognostic values of GSTM genes were identified by survival analysis. Function and mechanism of prognostic GSTM genes were identified by gene set enrichment analysis. A nomogram was used to predict the contribution of risk factors to the outcome of COAD patients. Results: Low expression of GSTM1 and GSTM2 was related to favorable OS (adjusted P = 0.006, adjusted HR = 0.559, 95% CI = 0.367–0.849 and adjusted P = 0.002, adjusted HR = 0.519, 95% CI = 0.342–0.790, respectively) after adjusting for tumor stage. Enrichment analysis also showed that genes involved were related to cell cycle, metabolism, and detoxification processes, as well as the Wnt signaling and NF-κB pathways. Conclusions: In conclusion, low expression of GSTM1 and GSTM2 were significantly associated with favorable prognosis in COAD. These two genes may serve as potential biomarkers of COAD prognosis. Keywords: GSTM, Prognosis, mRNA, Expression, Colon adenocarcinoma
Background Colon adenocarcinoma (COAD) is the most common form of colon cancer. There were 140,250 estimated new cases and 50,630 estimated deaths in 2018, and the five years survival rate is 64.5% as determined by the Surveillance, Epidemiology, and End Results Program (SEER; https://seer.cancer.gov) [1]. Alcohol consumption, smoking, and obesity are risk factors for colorectal cancers [2–4]. Identifying appropriate biomarkers for COAD patients prognosis is important. The glutathione S-transferase Mu (GSTM) gene family belongs to the * Correspondence: [email protected]; [email protected] 1 School of Public Health, Guangxi Medical University, 22 Shuang Yong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China Full list of author information is available at the end of the article
GST sub-family, which plays important roles in cell metabolism and detoxification [5–7]. GSTM is encoded by five genes (GSTM1–5) [8–11]. However, the correlation of GSTM with the prognosis of cancers is not clear, and there are no reports about the relationship between the GSTM family and COAD. In the present study, we investigated the expression of the GSTM gene family in COAD, and performed a survival analysis including clinical data. A nomogram model was used to predict the outcome of COAD, and joint-effects survival analysis was carried out to show that low expression of GSTM1 and GSTM2 was a sensitive predictor of favorable pr
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