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

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

doi:10.18632/oncotarget.13351

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.

Highlights

Esophageal cancer is the sixth main cause of cancerrelated mortality and the eighth most common cancer worldwide [1]
We aimed to investigate the pattern of expression and clinical significance of isocitrate dehydrogenase 1(IDH1) in esophageal squamous cell carcinoma (ESCC)
The results suggested that IDH1 expression was higher in cancerous tissues than in paracancerous tissues (Figure 2C, 2D, P < 0.001)

Summary

Introduction

Esophageal cancer is the sixth main cause of cancerrelated mortality and the eighth most common cancer worldwide [1]. The high-risk geographic region, referred to as the “esophageal cancer belt,” extends from Northern Iran to North Central China through Central Asia. In this region, more than 90% of the cases are identified as esophageal squamous cell carcinoma (ESCC), in contrast to only 26% in the United States [3]. A number of tumorspecific proteins have been identified as tumor markers for various cancers. These proteins include cancer antigen 125 (CA125) in ovarian cancer, alpha-fetoprotein (AFP) in liver cancer, carcinoembryonic antigen (CEA) in colon cancer, and prostate-specific antigen (PSA) in prostate cancer. New biomarkers with combined high sensitivity and good specificity for the diagnosis and prognosis in ESCC can provide enhanced clinical benefits

Objectives

Methods

Results

Conclusion