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

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.

Combination Susceptibility Testing of Common Antimicrobials in Vitro and the Effects of Sub-MIC of Antimicrobials on Staphylococcus aureus Biofilm Formation

“…These outcomes suggested that biofilm formation depends on biofilm-related genes and associated proteins under treatment with sub-MIC of antibiotics. And similar results have been reported previously (Bai et al, 2015 ; Chen et al, 2016 ). Nevertheless, the mechanisms by which drugs affect biofilm formation should be investigated further.…”

IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies

“…It is thought that the effect of IDH2 expression on neoplastic progression and drug resistance differs with respect to the site of origin and histological type. [50][51][52][53][54][55] Our study suggests the hypothesis that inhibition of wild-type IDH2 may have therapeutic potentials, regardless of IDH2 expression levels. Concordantly, we excluded that the IDH2 mutational status or its aberrant expression was associated to PI responsiveness in MM cells.…”

Low level of isocitrate dehydrogenase 1 predicts unfavorable postoperative outcomes in patients with clear cell renal cell carcinoma

“…In recent years, mutations in IDH1 gene were reported in various tumors, which confer IDH1 the new enzymatic function of catalyzing α-KG to R-2-hydroxyglutarate (2-HG) [ 29 ]. The role of IDH1 gene mutation in esophageal squamous cell carcinoma [ 30 ], glioma [ 31 ] and acute myeloid leukemia (AML) have been successively reported [ 32 ]. The expression level of IDH1-R132H, which is the most common mutation type, correlates with poor outcomes in several cancers, such as gastrointestinal cancer and nonenhancing diffuse glioma [ 16 , 33 ].…”