Department of Thoracic Surgery, Shanghai Jiaotong University First People's Hospital, 200080, Shanghai, People's Republic of China.
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 510060, Guangzhou, People's Republic of China.
Diagn Pathol. 2021 Jan 22;16(1):10. doi: 10.1186/s13000-021-01069-4.
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.
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.
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.
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.
谷胱甘肽 S-转移酶 mu3(GSTM3)在多种癌症的肿瘤进展中发挥着关键作用。然而,迄今为止,GSTM3 表达与食管鳞状细胞癌(ESCC)的临床预后之间的关系尚未得到研究。我们旨在探讨 GSTM3 在预测 ESCC 患者术后预后中的作用。
在回顾性研究中,通过实时定量 PCR 测定了 184 例 ESCC 组织和 43 例匹配的非肿瘤组织中的 GSTM3 mRNA 水平。通过免疫组织化学法测定了 247 例 ESCC 组织中的 GSTM3 蛋白水平。
与非肿瘤组织相比,原发性 ESCC 组织中 GSTM3 的表达下调了 62.8%。在 mRNA 队列(p=0.024)和蛋白队列(p=0.004)中,GSTM3 低表达的患者倾向于表现出更高的低分化率。在 mRNA 队列中,GSTM3 低表达与不利的 3 年无病生存率(DFS)(39.2%对 57.4%)和 5 年 DFS(26.8%对 45.1%)相关(p=0.023)。该结果在蛋白队列中得到了证实。GSTM3 低表达的患者 3 年无病生存率(DFS)(18.7%对 33.5%)和 5 年 DFS(5.3%对 30.5%)较差(p=0.006)。Cox 多变量分析显示,GSTM3 表达是独立的预后因素。
本研究的结果表明,GSTM3 可能在 ESCC 中作为肿瘤抑制因子发挥作用,是可切除 ESCC 患者无病生存率的潜在新型预后生物标志物。