Integrated Analysis of the Gene Expression Changes During Colorectal Cancer Progression by Bioinformatic Methods

摘要

We attempted to analyze the aberrant pathways and genes underlying the successive stages of colorectal cancer (CRC). The CRC related microarray data (GSE77953) were retrieved from Gene Expression Omnibus database, which included 17 colonic adenoma, 17 carcinoma, 11 CRC metastases, and 13 normal colonic epithelium samples. The differential expression patterns in colonic adenoma, carcinoma, and metastases were analyzed. Gene functional interaction (FI) and coexpressed network were constructed. Pathway enrichment analysis was performed to investigate the perturbed pathways, and disease-related genes were explored based on the Comparative Toxicogenomics Database. Total 438 genes were identified to be differentially expressed in colonic adenoma, 885 in carcinoma and 736 in metastases. The upregulated genes in adenoma were significantly related with ribosome, oxidative phosphorylation, and protein export related pathways. The downregulated genes in carcinoma and metastases were enriched in the same pathways, such as nitrogen metabolism, mineral absorption, and steroid hormone biosynthesis. FI network was constructed with 219 and 3914 edges, which were further divided to 12 modules. The genes in module 0 were closely related with ribosome, protein export, and RNA transport. Coexpressed genes were enriched in ribosome, protein export, and mineral absorption pathways. Total eight common upregulated genes were found to be the CRC-related genes such as RNF43 (ring finger protein 43), EIF3H (eukaryotic translation initiation factor 3 subunit H), and STRAP (serine/threonine kinase receptor associated protein). The common downregulated genes included ABCG2 (ATP binding cassette subfamily G member 2), GCG (glucagon), and SULT1A1 (sulfotransferase family 1A member 1). Oxidative phosphorylation, nitrogen metabolism, mineral absorption, and protein synthesis may significantly be perturbed in the progression of CRC. The overexpression of EIF3H may be the predictor for CRC formation.