Expression of ERCC1, TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal squamous cell carcinoma: A hierarchical clustering analysis

Yongkang Yu,Lie Yang,Yifeng Zheng,Jianqing Jiang,Yu Liang,Sheng Ding,Wei Li,Xiushan Zheng

doi:10.3892/etm.2014.1659

Abstract

The aim of the present study was to investigate the correlation between the expression levels of excision repair cross complementing 1 (ERCC1), thymidylate synthase (TYMS), class III β-tubulin (TUBB3), ribonucleoside-diphosphate reductase (RRM1) and topoisomerase IIα (TOP2A) with the clinical characteristics of patients with esophageal squamous cell carcinoma (ESCC). A total of 29 ESCC tissue samples were collected from patients that had not previously received systematic treatment. The expression levels of ERCC1, TYMS, TUBB3, RRM1 and TOP2A were determined using a microarray technique, while Spearman’s rank correlation analysis was used to determine the strength of the correlations between the expression levels of the biomarkers and the pathogenesis of esophageal cancer. High expression levels of TYMS and TOP2A were observed in 24% of the samples and high expression levels of TUBB3 and RRM1 were identified in 7% of the samples. Hierarchical clustering analysis of these biomarkers enabled the samples to be grouped. Group 1 patients exhibited low expression levels of TYMS, RRM1 and TOP2A and high expression of ERCC1 and TUBB3, while group 2 samples had low expression levels of ERCC1 and TUBB3 and high expression levels of TYMS, RRM1 and TOP2A. Analysis using Fisher’s exact test demonstrated a statistically significant difference in the severity of carcinoma invasion between the two groups (P<0.05), however, no significant differences were identified with regard to the clinical stage or lymphatic metastasis (P>0.05). Therefore, hierarchical clustering analysis indicated that the expression levels of ERCC1, TYMS, TUBB3, RRM1 and TOP2A were closely associated with the clinical characteristics of patients with ESCC.

Highlights

Esophageal cancer (EC) is the third most common type of gastrointestinal malignancy and has been considered as a leading cause for cancer‐induced mortality worldwide
High expression levels of thymidylate synthase (TYMS) and TOP2A were observed in 24.14% of the samples, while high expression levels of TUBB3 and RRM1 were observed in 6.9% of the samples (Table II)
To the best of our knowledge, no study has been conducted investigating the expression of excision repair cross complementing 1 (ERCC1), TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal squamous cell carcinoma (ESCC)

Summary

Introduction

Esophageal cancer (EC) is the third most common type of gastrointestinal malignancy and has been considered as a leading cause for cancer‐induced mortality worldwide. Recent studies have been conducted with regard to the screening of tumor biomarkers in the pathogenesis and prognosis of various types of carcinomas. Low expression of RRM1 is associated with a poor survival rate among patients with non‐small‐cell lung cancer (NSCLC) [3]. ERCC1 mRNA expression levels are associated with non‐response and/or survival rates of patients with colon cancer and NSCLC [4,5]. The topoisomerase IIα (TOP2A) gene encodes an enzyme that is involved in DNA replication, and is associated with the sensitivity to anthracycline therapy in various carcinomas. To the best of our knowledge no study has been conducted using ERCC1, TYMS, TUBB3, RRM1 and TOP2A simultaneously in esophageal squamous cell carcinoma (ESCC)

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