Identification of key gene modules and genes in colorectal cancer by co-expression analysis weighted gene co-expression network analysis

Peng Wang,Xiaoyan Xuan,Jiayu Zhang,Huaixin Zheng,Pingping Liu,Ying Du,Qianru Li,Yashu Wang

doi:10.1042/bsr20202044

Abstract

Colorectal cancer (CRC) has been one of the most common malignancies worldwide, which tends to get worse for the growth and aging of the population and westernized lifestyle. However, there is no effective treatment due to the complexity of its etiology. Hence, the pathogenic mechanisms remain to be clearly defined. In the present study, we adopted an advanced analytical method—Weighted Gene Co-expression Network Analysis (WGCNA) to identify the key gene modules and hub genes associated with CRC. In total, five gene co-expression modules were highly associated with CRC, of which, one gene module correlated with CRC significantly positive (R = 0.88). Functional enrichment analysis of genes in primary gene module found metabolic pathways, which might be a potentially important pathway involved in CRC. Further, we identified and verified some hub genes positively correlated with CRC by using Cytoscape software and UALCAN databases, including PAICS, ATR, AASDHPPT, DDX18, NUP107 and TOMM6. The present study discovered key gene modules and hub genes associated with CRC, which provide references to understand the pathogenesis of CRC and may be novel candidate target genes of CRC.

Highlights

Besides lung cancer and breast cancer, colorectal cancer (CRC) is the most commonly diagnosed malignant cancer worldwide, which accounts for over 9% of all cancer incidences [1]
Due to its distinct advantages, Weighted Gene Co-expression Network Analysis (WGCNA) has been widely utilized to discover the synergetically expressed modules and candidate key hub genes associated with various diseases, such as allergic asthma [7], T-cell lymphoma [17], osteosarcoma [18], hepatocellular carcinoma [19], uveal melanoma [20] and other cancers
There is almost no relevant paper adopting WGCNA approach to investigate hub genes associated with CRC pathogenesis

Summary

Introduction

Besides lung cancer and breast cancer, colorectal cancer (CRC) is the most commonly diagnosed malignant cancer worldwide, which accounts for over 9% of all cancer incidences [1]. It is the fourth leading cause of cancer deaths in men and the third in women in the world, which accounted for nearly 8% of all cancer deaths in 2012 [1,2,3]. It has been recognized that CRC risks are closely associated with environmental factors and gene mutations. The pathogenesis of CRC has not been well revealed, as it is a heterogeneous disease associated with multiple genes and pathways. Deep and systematic understanding of genetic etiology and pathology of CRC, which may find new candidate target genes and provide new potential treatment strategies and methods

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Conclusion