Low GSTM3 expression is associated with poor disease-free survival in resected esophageal squamous cell carcinoma

Diagn Pathol. 2021 Jan 22;16(1):10. doi: 10.1186/s13000-021-01069-4.

Abstract

Background: Glutathione 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.

Methods: In 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.

Results: Downregulation 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.

Conclusions: The 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.

Keywords: Biomarker; Disease‐free survival; Esophageal squamous cell carcinoma; Glutathione S-transferase mu 3; Prognosis.

MeSH terms

  • Cohort Studies
  • Disease-Free Survival
  • Down-Regulation
  • Esophageal Neoplasms / diagnosis*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / diagnosis*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Retrospective Studies
  • Tissue Array Analysis

Substances

  • GSTM3 protein, human
  • Glutathione Transferase