Sun Xuren, Sun Zhe, Zhu Zhi, Li Chenyan, Zhang Junyan, Xu Huimian, Sun Mingjun
Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Surgical Oncology, First Affiliated Hospital of China Medical University, Shenyang, China.
Tumour Biol. 2015 Sep;36(10):7521-30. doi: 10.1007/s13277-015-3470-7. Epub 2015 Apr 26.
Smad interacting protein 1 (SIP1) plays an important role in the epithelial-mesenchymal transition (EMT) process by downregulating E-cadherin. Lactate dehydrogenase A (LDHA) is a crucial enzyme that plays an important role in the final step of the Warburg effect by converting pyruvate to lactate irreversibly. EMT and Warburg effect are the hallmarks of advanced gastric cancer progression. Recently, EMT has been thought to be implicated in cancer metabolism. In this study, we want to find whether there was a correlation between the expressions of SIP1 and LDHA in gastric cancer and whether expression of SIP1 alone or in combination with LDHA is associated with the progression of gastric cancer. In the present study, we examined SIP1 and LDHA expression by immunohistochemistry analysis on tissue microarray (TMA) containing tumor tissues and matched non-neoplastic mucosa (NNM). Prognostic value and correlation with other clinicopathologic factors were evaluated. In this study, we investigated the expression of SIP1 and LDHA in 261 cancer tissues and their matched NNM using tissue microarray. The immunohistochemistry analysis showed that the expression of SIP1 and LDHA was significantly higher in cancer tissues than in NNM (P = 0.002 P = 0.000, respectively). The expression of SIP1was significantly associated with age, Lauren grade, and histologic differentiation (P < 0.05). The expression of SIP1 was strongly correlated with LDHA expression in gastric cancer (P = 0.000, R = 0.589). The combined expression of SIP1 and LDHA was significantly associated with age, Lauren grade, and histologic differentiation (P < 0.05). Survival analysis demonstrated that the expression of SIP1 or LDHA was associated with significantly shorter overall survival (OS) (P = 0.003, P = 0.000, respectively) and disease-free survival (DFS) (P = 0.003, P = 0.000, respectively). The combined expression of SIP1 and LDHA was associated with less survival time in gastric cancer patients (P = 0.000). The multivariate analysis showed that the expressions of SIP1 and LDHA in gastric cancer (GC) were independent prognostic factors for OS (hazard ratio = 1.465, 95 %CI 1.128-1.901, P = 0.004, hazard ratio = 1.514, 95 %CI 1.091-2.101 P = 0.013, respectively) and DFS (hazard ratio = 1.461, 95 %CI 1.130-1.890, P = 0.004, hazard ratio = 1.550 95 %CL1.119-2.147 P = 0.008, respectively). Our study indicated that expressions of SIP1 and LDHA are independent prognostic factors in gastric cancer patients and may be predictive of poor outcomes.
Smad相互作用蛋白1（SIP1）通过下调E-钙黏蛋白在上皮-间质转化（EMT）过程中发挥重要作用。乳酸脱氢酶A（LDHA）是一种关键酶，通过将丙酮酸不可逆地转化为乳酸，在瓦伯格效应的最后一步中发挥重要作用。EMT和瓦伯格效应是进展期胃癌的标志。最近，EMT被认为与癌症代谢有关。在本研究中，我们想探究胃癌中SIP1和LDHA的表达之间是否存在相关性，以及单独的SIP1表达或与LDHA联合表达是否与胃癌进展相关。在本研究中，我们通过免疫组织化学分析检测了包含肿瘤组织和配对的非肿瘤黏膜（NNM）的组织微阵列（TMA）上的SIP1和LDHA表达。评估了其预后价值以及与其他临床病理因素的相关性。在本研究中，我们使用组织微阵列研究了261例癌组织及其配对的NNM中SIP1和LDHA的表达。免疫组织化学分析显示，SIP1和LDHA在癌组织中的表达显著高于NNM（P分别为0.002和0.000）。SIP1的表达与年龄、劳伦分级和组织学分化显著相关（P<0.05）。胃癌中SIP1的表达与LDHA表达密切相关（P = 0.000，R = 0.589）。SIP1和LDHA的联合表达与年龄、劳伦分级和组织学分化显著相关（P<0.05）。生存分析表明，SIP1或LDHA的表达与总生存期（OS）显著缩短相关（P分别为0.003和0.000）以及无病生存期（DFS）（P分别为0.003和0.000）。SIP1和LDHA的联合表达与胃癌患者的生存期缩短相关（P = 0.000）。多因素分析显示，胃癌（GC）中SIP1和LDHA的表达是OS（风险比=1.465，95%CI 1.128 - 1.901，P = 0.004，风险比=1.514，95%CI 1.091 - 2.101，P = 0.013）和DFS（风险比=1.461，95%CI 1.130 - 1.890，P = 0.004，风险比=1.550，95%CL1.119 - 2.147，P = 0.008）的独立预后因素。我们的研究表明，SIP1和LDHA的表达是胃癌患者的独立预后因素，可能预示不良预后。
