The clinical significance of isocitrate dehydrogenase 2 in esophageal squamous cell carcinoma.

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 P<0.001) despite no significant difference at mRNA expression level (P>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), P = 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 P<0.005) in ESCC. The OD450 value, colony formation and invasive cell number were decreased in the shIDH2 groups (all P<0.0001). The upregulation of IDH2 in ESCC cells showed opposite effects (all P<0.05). Additionally, IDH2 knockdown phenotype can be rescued by shRNA-resistant IDH2 (all P<0.05). These results demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable prognostic marker for ESCC patients.