title: The clinical significance of isocitrate dehydrogenase 2 in esophageal squamous cell carcinoma.
abstract: 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, allP<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 (allP<0.005) in ESCC. The OD450value, colony formation and invasive cell number were decreased in the shIDH2 groups (allP<0.0001). The upregulation of IDH2 in ESCC cells showed opposite effects (allP<0.05). Additionally, IDH2 knockdown phenotype can be rescued by shRNA-resistant IDH2 (allP<0.05). These results demonstrated that IDH2 was upregulated in ESCC and could be used as a valuable prognostic marker for ESCC patients.
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Imaging, Shandong Medical College Jinan 250002, Shandong, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Shanghui
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute Jinan 250117, Shandong, China.
authors.forename: Xintong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute Jinan 250117, Shandong, China.
authors.forename: Dianzheng
authors.initials: D
authors.lastname: An
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Pengxiang
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Qilu Hospital of Shandong University Jinan 250012, Shandong, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Cheng
keywords: ESCC; IDH2; expression; prognosis