Differential connectivity in colorectal cancer gene expression network

Abstract

Background: Colorectal cancer (CRC) is one of the challenging types of cancers; thus, exploring effective biomarkers related to colorectal could lead to significant progresses toward the treatment of this disease. Methods: In the present study, CRC gene expression datasets have been reanalyzed. Mutual differentially expressed genes across 294 normal mucosa and adjacent tumoral samples were then utilized in order to build two independent transcriptional regulatory networks. By analyzing the networks topologically, genes with differential global connectivity related to cancer state were determined for which the potential transcriptional regulators including transcription factors were identified. Results: The majority of differentially connected genes (DCGs) were up-regulated in colorectal transcriptome experiments. Moreover, a number of these genes have been experimentally validated as cancer or CRC-associated genes. The DCGs, including GART, TGFB1, ITGA2, SLC16A5, SOX9, and MMP7, were investigated across 12 cancer types. Functional enrichment analysis followed by detailed data mining exhibited that these candidate genes could be related to CRC by mediating in metastatic cascade in addition to shared pathways with 12 cancer types by triggering the inflammatory events. Conclusion: Our study uncovered correlated alterations in gene expression related to CRC susceptibility and progression that the potent candidate biomarkers could provide a link to disease.