Liu Dongzhe, Sun Liang, Tong Jinxue, Chen Xiuhui, Li Hui, Zhang Qifan
1 Department of Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
2 Harbin Medical University, Harbin, China.
Tumour Biol. 2017 Jun;39(6):1010428317701443. doi: 10.1177/1010428317701443.
Increasing evidence suggests that the glutathione peroxidase 2 may actually play important roles in tumorigenesis and progression in various human cancers such as colorectal carcinomas and lung adenocarcinomas. However, the role of glutathione peroxidase 2 in gastric carcinoma remains to be determined. In this study, the expression and prognostic significance of glutathione peroxidase 2 in gastric carcinoma were investigated and the well-known prognostic factor Ki-67 labeling index was also assessed as positive control. Glutathione peroxidase 2 expression levels in the tumor tissue specimens, the matched adjacent normal tissue specimens, and the lymph node metastases of 176 patients with gastric carcinoma were evaluated by quantitative polymerase chain reaction, western blotting, and immunohistochemical staining. The associations between glutathione peroxidase 2 expression levels, as determined by immunohistochemical staining, and multiple clinicopathological characteristics were determined by Pearson's chi-square test and Spearman's correlation analysis. The relationships between glutathione peroxidase 2 expression and other clinicopathological variables and patient prognoses were analyzed further by the Kaplan-Meier method, the log-rank test, and Cox multivariate regression. The quantitative polymerase chain reaction, western blotting, and immunohistochemical staining results showed that glutathione peroxidase 2 expression levels were upregulated in both the primary tumor foci and the lymph node metastases of patients with gastric carcinoma (all p values < 0.05). Furthermore, Pearson's chi-square tests, as well as Spearman's correlation analysis, revealed that glutathione peroxidase 2 expression levels were strongly correlated with the Ki-67 labeling index, differentiation, histological patterns, Lauren classifications, lymph node metastasis, vascular invasion, tumor-node-metastasis stages, Helicobacter pylori infection, and overall survival (all p values < 0.05). Kaplan-Meier analysis, as well as the log-rank test and multivariate Cox regression analysis, showed that multiple clinicopathological risk factors and glutathione peroxidase 2 expression were novel independent prognostic factors for gastric carcinoma (all p values < 0.05). Glutathione peroxidase 2 expression is a novel independent prognostic biomarker for gastric carcinoma that may be used to devise personalized therapeutic regimens and precision treatments for this disease.
越来越多的证据表明，谷胱甘肽过氧化物酶2实际上可能在多种人类癌症（如结直肠癌和肺腺癌）的肿瘤发生和进展中发挥重要作用。然而，谷胱甘肽过氧化物酶2在胃癌中的作用仍有待确定。在本研究中，对谷胱甘肽过氧化物酶2在胃癌中的表达及其预后意义进行了研究，并将著名的预后因子Ki-67标记指数作为阳性对照进行了评估。通过定量聚合酶链反应、蛋白质印迹法和免疫组织化学染色，对176例胃癌患者的肿瘤组织标本、配对的相邻正常组织标本以及淋巴结转移灶中的谷胱甘肽过氧化物酶2表达水平进行了评估。通过Pearson卡方检验和Spearman相关性分析，确定了免疫组织化学染色所测定的谷胱甘肽过氧化物酶2表达水平与多种临床病理特征之间的关联。通过Kaplan-Meier法、对数秩检验和Cox多因素回归进一步分析了谷胱甘肽过氧化物酶2表达与其他临床病理变量及患者预后之间的关系。定量聚合酶链反应、蛋白质印迹法和免疫组织化学染色结果显示，胃癌患者的原发性肿瘤灶和淋巴结转移灶中谷胱甘肽过氧化物酶2表达水平均上调（所有p值<0.05）。此外，Pearson卡方检验以及Spearman相关性分析显示，谷胱甘肽过氧化物酶2表达水平与Ki-67标记指数、分化程度、组织学类型、Lauren分类、淋巴结转移、血管侵犯、肿瘤-淋巴结-转移分期、幽门螺杆菌感染及总生存期均密切相关（所有p值<0.05）。Kaplan-Meier分析以及对数秩检验和多因素Cox回归分析显示，多种临床病理危险因素和谷胱甘肽过氧化物酶2表达是胃癌新的独立预后因素（所有p值<0.05）。谷胱甘肽过氧化物酶2表达是胃癌新的独立预后生物标志物，可用于制定针对该疾病的个性化治疗方案和精准治疗。
