Microarray analysis of differentially-expressed genes and linker genes associated with the molecular mechanism of colorectal cancer.

Abstract

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and remains the third leading cause of cancer-associated mortality. The present study aimed to fully elucidate the pathogenesis of CRC and identify associated genes in tumor development. Microarray GSE44076, GSE41328 and GSE44861 datasets were downloaded from the Gene Expression Omnibus database and integrated with meta-analysis. Differentially-expressed genes (DEGs) were identified from CRC samples compared with adjacent non-cancerous controls using the Limma package in R, followed by functional analysis using the Database for Annotation, Visualization, and Integrated Discovery online tool. A protein-protein interaction (PPI) network of DEGs and linker genes was constructed using NetBox software and modules were also mined. Functional annotation was performed for modules with a maximum number of nodes. Subsequent to meta-analysis to pool the data, one dataset that included 327 samples involved in 11,081 genes was obtained. A total of 697 DEGs were identified between CRC samples and adjacent non-cancerous controls. In the PPI network, modules 1 and 5 contained the maximum number of nodes. Collagen, type I, α1 (COL1A1), COL1A2 and matrix metallopeptidase 9 (MMP9) in module 1 and UDP-glucose 6-dehydrogenase (UGDH), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), fatty acid binding protein 4 (FABP4) and monoglyceride lipase (MGLL) in module 5 exhibited a high degree of connectivity. Functional analysis indicated that the genes in module 1 were involved in extracellular matrix (ECM)-associated functions and that the genes in module 5 were involved in metabolism-related functions. Overall, significant DEGs and linker genes, namely COL1A1, COL1A2, MMP9, UGDH, ALDH1A1, FABP4 and MGLL, play a crucial role in the development of CRC via regulating the ECM and cell metabolism.