Abstract
BackgroundGlutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. However, the relationship between GSTM3 expression and the clinical prognosis of esophageal squamous cell carcinoma (ESCC) has not been studied to date. We aimed to characterize the role of GSTM3 in predicting postoperative prognosis of ESCC patients.MethodsIn the retrospective study, GSTM3 mRNA levels in 184 ESCC tissues and matched 43 adjacent nontumorous tissues were measured by quantitative real-time PCR. GSTM3 protein levels in 247 ESCC tissues were measured by immunohistochemistry.ResultsDownregulation of GSTM3 occurred in 62.8 % of primary ESCC tissues compared with their nontumor counterparts. Patients with low GSTM3 expression tended to exhibit an increased rate of poor differentiation in both the mRNA cohort (p = 0.024) and protein cohort (p = 0.004). In the mRNA cohort, low GSTM3 expression was associated with unfavorable 3-year disease-free survival (DFS) (39.2 % vs. 57.4 %) and 5-year DFS (26.8 % vs. 45.1 %) (p = 0.023). The result was confirmed in the protein cohort. Patients with low GSTM3 expression had unfavorable 3-year disease-free survival (DFS) (18.7 % vs. 33.5 %) and 5-year DFS (5.3 % vs. 30.5 %) (p = 0.006). Cox multivariate analysis revealed that GSTM3 expression was an independent prognostic factor.ConclusionsThe findings of the present study provide evidence that GSTM3 may function as a tumor suppressor in ESCC and represents a potential novel prognostic biomarker for disease-free survival for resected ESCC patients.
Highlights
Glutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers
Total RNA was extracted from clinical samples using TRIzol reagent (Invitrogen) according to the manufacturer’s instruction. cDNA was synthesized from 1 μg of total RNA using RevertAid First Strand cDNA Synthesis Kit (Thermo Scientific) and stored at -80°C. cDNA was subjected to quantitative real-time PCR for GSTM3
GSTM3 mRNA expression was initially tested in 43 pairs of primary esophageal squamous cell carcinoma (ESCC) tumors and their adjacent nontumorous tissues by Quantitative real‐time Polymerase Chain Reaction (qPCR)
Summary
Glutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. Esophageal cancer has 2 major histologic types: squamous cell carcinoma (SCC) and adenocarcinoma (ACE) [3]. Patients with ESCC are at increased risk of developing second primary cancers, such as head and neck tumors and lung cancer [8]. This feature suggests that the oxidation-reduction system of patients with ESCC may be impaired. The correlation between GST enzyme activity and tumor incidence has been demonstrated in the esophageal squamous cell carcinoma, esophageal adenocarcinoma, gastric cancer and colorectal cancer [11,12,13,14,15]
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