Abstract
Colorectal cancer (CRC) is one of the most common tumors worldwide and is associated with high mortality. Here we performed bioinformatics analysis, which we validated using immunohistochemistry in order to search for hub genes that might serve as biomarkers or therapeutic targets in CRC. Based on data from The Cancer Genome Atlas (TCGA), we identified 4832 genes differentially expressed between CRC and normal samples (1562 up-regulated and 3270 down-regulated in CRC). Gene ontology (GO) analysis showed that up-regulated genes were enriched mainly in organelle fission, cell cycle regulation, and DNA replication; down-regulated genes were enriched primarily in the regulation of ion transmembrane transport and ion homeostasis. Weighted gene co-expression network analysis (WGCNA) identified eight gene modules that were associated with clinical characteristics of CRC patients, including brown and blue modules that were associated with cancer onset. Analysis of the latter two hub modules revealed the following six hub genes: adhesion G protein-coupled receptor B3 (BAI3, also known as ADGRB3), cyclin F (CCNF), cytoskeleton-associated protein 2 like (CKAP2L), diaphanous-related formin 3 (DIAPH3), oxysterol binding protein-like 3 (OSBPL3), and RERG-like protein (RERGL). Expression levels of these hub genes were associated with prognosis, based on Kaplan–Meier survival analysis of data from the Gene Expression Profiling Interactive Analysis database. Immunohistochemistry of CRC tumor tissues confirmed that OSBPL3 is up-regulated in CRC. Our findings suggest that CCNF, DIAPH3, OSBPL3, and RERGL may be useful as therapeutic targets against CRC. BAI3 and CKAP2L may be novel biomarkers of the disease.
Highlights
Colorectal cancer (CRC), which includes colon and rectal cancers, is one of the most common cancers of the digestive system [1]
Some studies have used Weighted gene co-expression network analysis (WGCNA) to explore molecular markers related to its pathogenesis, diagnosis and prognosis [34,35,36], the present work provided a more complete novel idea
We performed bioinformatics analyses across independent patient cohorts to identify biomarkers, one of Consistent with the predicted functional enrichment of our CRC differentially expressed gene (DEG) genes, the cell cycle has been shown to be dysregulated in many types of cancer [37]
Summary
Colorectal cancer (CRC), which includes colon and rectal cancers, is one of the most common cancers of the digestive system [1]. It is the second leading cause of cancer-related mortality and the third leading cause of cancer-related incidence worldwide [2]. It occurs in three histopathological types, including adenocarcinoma, squamous cell carcinoma, and mucinous carcinoma; adenocarcinoma is the most common type, accounting for ∼95% of all CRC cases [3]. Up to 15% of CRC cases involve DNA microsatellite instability, which leads to DNA replication errors [8]
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