The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis.

Jingwei Liu,Hao Li,Zhenning Wang,Yuan Yuan,Xue Feng,Liping Sun,Chengzhong Xing

doi:10.1155/2018/9651320

Abstract

Background Nucleotide excision repair (NER) plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development. Method Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. Results ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5 expression indicated deeper T stage and distant metastasis; DDB2 expression suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS) in colon cancer (HR = 1.53, P = 0.043). Colon cancer patients with high ERCC4 expression showed favorable OS in males (HR = 0.54, P = 0.035). High XPC expression demonstrated decreased death hazards in rectal cancer (HR = 0.40, P = 0.026). Conclusion ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis.

Highlights

As one of the leading cause of cancer-related mortality worldwide, colorectal cancer (CRC) develops from normal epithelial cells through benign adenomas to malignant carcinomas [1]
ERCC1, ERCC2, ERCC5, and DDB2 were highly expressed in CRC tissues compared to matched normal tissues, while ERCC4 was found to be downregulated in CRC (Table 2)
Nucleotide excision repair (NER) consists of transcription-coupled nucleotide excision repair (TCNER) and global genome nucleotide excision repair (GGNER) [20], each step of which requires specific NER members to accomplish functions including

Summary

Introduction

As one of the leading cause of cancer-related mortality worldwide, colorectal cancer (CRC) develops from normal epithelial cells through benign adenomas to malignant carcinomas [1]. Unrepaired DNA damage would have deleterious effects to normal biological functions of cells and contribute to the development of CRC [12]. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development. Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC. ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS) in colon cancer (HR = 1.53, P = 0.043). ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis

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Results