Chen Xuan, Xu Wenzhe, Wang Cong, Liu Fang, Guan Shanghui, Sun Yi, Wang Xintong, An Dianzheng, Wen Zhihua, Chen Pengxiang, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
Department of Neurosurgery, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
Am J Cancer Res. 2017 Mar 1;7(3):700-714. eCollection 2017.
Isocitrate dehydrogenase 2 (IDH2) is the rate-limiting enzyme in the tricarboxylic acid (TCA) cycle in cellular metabolism. Growing evidence indicates that IDH2 plays a crucial role in the development of cancer. We aimed to investigate the expression level of IDH2 and its prognostic value in esophageal squamous cell cancer (ESCC). We evaluate the IDH2 expression and prognostic value in ESCC by immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK8), clonogenic and invasion assays were performed to verify the IDH2 function in vitro. The protein expression level of IDH2 was significantly upregulated in ESCC tissues (IHC, Western blotting, all <0.001) despite no significant difference at mRNA expression level (>0.05). Kaplan-Meier analysis showed that IDH2 overexpression in ESCC patients was significantly related to worse overall survival (OS) and progression-free survival (PFS), = 0.003 and 0.002, respectively. The univariate and multivariate analyses revealed that IDH2 overexpression served as an independent prognostic factor for OS and PFS (all <0.005) in ESCC. The OD value, colony formation and invasive cell number were decreased in the shIDH2 groups (all <0.0001). The upregulation of IDH2 in ESCC cells showed opposite effects (all <0.05). Additionally, IDH2 knockdown phenotype can be rescued by shRNA-resistant IDH2 (all <0.05). These results demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable prognostic marker for ESCC patients.
异柠檬酸脱氢酶2（IDH2）是细胞代谢中三羧酸（TCA）循环的限速酶。越来越多的证据表明，IDH2在癌症发展中起关键作用。我们旨在研究IDH2在食管鳞状细胞癌（ESCC）中的表达水平及其预后价值。我们通过免疫组织化学（IHC）染色、定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法评估ESCC中IDH2的表达及其预后价值。进行细胞计数试剂盒-8（CCK8）、克隆形成和侵袭试验以在体外验证IDH2的功能。尽管mRNA表达水平无显著差异（>0.05），但ESCC组织中IDH2的蛋白表达水平显著上调（IHC、蛋白质免疫印迹法，均<0.001）。Kaplan-Meier分析表明，ESCC患者中IDH2过表达与较差的总生存期（OS）和无进展生存期（PFS）显著相关，分别为=0.003和0.002。单因素和多因素分析显示，IDH2过表达是ESCC患者OS和PFS的独立预后因素（均<0.005）。shIDH2组的光密度值、集落形成和侵袭细胞数均降低（均<0.0001）。ESCC细胞中IDH2的上调显示出相反的效果（均<0.05）。此外，IDH2敲低表型可被抗shRNA的IDH2挽救（均<0.05）。这些结果表明，IDH2在ESCC中上调，可作为ESCC患者有价值的预后标志物。
