AbstractAdenocarcinoma of the colon is the fourth most common malignancy worldwide with significant rates of mortality. Hence, the identification of novel molecular biomarkers with prognostic significance is of particular importance for improvements in treatment and patient outcome. Clinical traits and RNA-Seq data of 551 patient samples and 18,205 genes in the UCSC Toil Recompute Compendium of TCGA TARGET and GTEx datasets (restricted to |Primary_site| = colon) were obtained from the Xena platform. Weighted gene co-expression network analysis was completed, and 24 unique modules were assembled to specifically examine the association between gene networks and cancer cell invasion. One module, containing 151 genes, was significantly correlated with lymphatic invasion, a histopathological feature of higher-risk colon cancer. Search tool for the retrieval of interacting genes/proteins (STRING) and gene ontology (GO) analyses identified the module to be enriched in genes related to cytoskeletal organization and apoptotic signaling, suggesting involvement in tumor cell survival and migration along with epithelial-mesenchymal transformation. Of genes that were differentially expressed and significant for overall survival, DAPK3 (death-associated protein kinase 3) was revealed as the pseudo-hub of the module. Although DAPK3 expression was reduced in colon cancer patients, survival analysis revealed that high expression of DAPK3 was significantly correlated with greater lymphovascular invasion and poor overall survival.
Network analysis identifies DAPK3 as a potential biomarker for lymphovascular invasion and prognosis of colon adenocarcinoma
