Chen Xuan, Li Qingbao, Wang Cong, Xu Wenzhe, Han Lihui, Liu Yuan, Liu Bowen, Guan Shanghui, Tan Bingxu, Wang Jianbo, Wang Nana, Song Qingxu, Jia Yibin, Wang Jianzhen, Zhao Linli, Cheng Yufeng
Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
Department of Cardiac Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, China.
Oncotarget. 2016 Dec 27;7(52):86148-86160. doi: 10.18632/oncotarget.13351.
We aimed to investigate the pattern of expression and clinical significance of isocitrate dehydrogenase 1(IDH1) in esophageal squamous cell carcinoma (ESCC). The IDH1 expression was determined by quantitative real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis using 38 pairs of frozen tissues. Enzyme-linked immunosorbent assay was employed to measure 67 pairs of serum samples from patients and their controls to evaluate its diagnostic value. Immunohistochemistry analysis of 111 formalin-fixed paraffin embedded tissue samples was conducted for explaining its prognostic value. After shRNA transfection, CCK8 and clonal efficiency assays were carried on for verifying the function of IDH1 in vitro. Increased expression at mRNA (P < 0.001) and protein levels (immunohistochemistry: P < 0.001, Western blot analysis: P < 0.001) were observed. Similarly, the IDH1 expression in serum from patients with ESCC was significantly upregulated relative to that from healthy controls (P < 0.001). Kaplan-Meier curve indicated that IDH1 upregulation predicted worse overall survival (OS) and progression-free survival (PFS). Univariate and multivariate analyses identified IDH1 expression as an independent prognostic factor for OS and PFS. Furthermore, OD450 values and colony numbers were decreased in sh-IDH1 groups (all P < 0.05). In conclusion, IDH1 is upregulated in patients with ESCC and can be used as a good potential biomarker for diagnosis and prognosis.
我们旨在研究异柠檬酸脱氢酶1（IDH1）在食管鳞状细胞癌（ESCC）中的表达模式及其临床意义。采用定量实时聚合酶链反应、免疫组织化学和蛋白质印迹分析方法，对38对冷冻组织样本进行IDH1表达检测。采用酶联免疫吸附测定法检测67对患者及其对照的血清样本，以评估其诊断价值。对111份福尔马林固定石蜡包埋组织样本进行免疫组织化学分析，以阐释其预后价值。shRNA转染后，进行CCK8和克隆形成率测定以验证IDH1在体外的功能。结果观察到，IDH1在mRNA水平（P < 0.001）和蛋白质水平（免疫组织化学：P < 0.001，蛋白质印迹分析：P < 0.001）均呈表达增加。同样，ESCC患者血清中的IDH1表达相对于健康对照显著上调（P < 0.001）。Kaplan-Meier曲线表明，IDH1上调预示总生存期（OS）和无进展生存期（PFS）较差。单因素和多因素分析确定IDH1表达为OS和PFS的独立预后因素。此外，sh-IDH1组的OD450值和集落数均降低（均P < 0.05）。总之，ESCC患者中IDH1上调，可作为诊断和预后的良好潜在生物标志物。
