Prognostic and diagnostic potential of isocitrate dehydrogenase 1 in esophageal squamous cell carcinoma

异柠檬酸脱氢酶1在食管鳞状细胞癌中的预后和诊断潜力

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作者:Xuan Chen, Qingbao Li, Cong Wang, Wenzhe Xu, Lihui Han, Yuan Liu, Bowen Liu, Shanghui Guan, Bingxu Tan, Jianbo Wang, Nana Wang, Qingxu Song, Yibin Jia, Jianzhen Wang, Linli Zhao, Yufeng Cheng

Abstract

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.

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