LAUSR

AIMS Due to a large number of identified hub-genes, encoding key molecular regulators, which involve in signal transduction and metabolic pathways in cancers, it is relevant to systemize and update these findings. BACKGROUND Colorectal cancer (CRC) is the third leading cause of cancer death in the world with high metastatic potential. Elucidating the pathogenic mechanisms and selection of novel biomarkers in CRC is of great clinical significance. OBJECTIVE This analytical review aims at systematization of bioinformatics and experimental identification of hub-genes, associated with CRC, for a more consolidated understanding of common features in networks and pathways in CRC progression as well as hub-genes selection. RESULTS In total, 301 hub-genes were derived from 40 articles. The "core" consisted of 28 hub-genes (CCNB1, LPAR1, BGN, CXCL3, COL1A2, UBE2C, NMU, COL1A1, CXCL2, CXCL11, CDK1, TOP2A, AURKA, SST, CXCL5, MMP3, CCND1, TIMP1, CXCL8, CXCL1, CXCL12, MYC, CCNA2, GCG, GUCA2A, PAICS, PYY and THBS2) mentioned in not less than three articles and having clinical significance in cancer-associated pathways. Of them, there were two discrete clusters enriched in chemokine signaling and cell cycle regulation genes. High expression levels of BGN and TIMP1 and low expression levels of CCNB1, CXCL3, CXCL2, CXCL2 and PAICS were associated with unfavorable overall survival of patients with CRC. Differently expressed genes such as LPAR1, SST, CXCL12, GUCA2A, and PYY were shown as down regulated, whereas BGN, CXCL3, UBE2C, NMU, CXCL11, CDK1, TOP2A, AURKA, MMP3, CCND1, CXCL1, MYC, CCNA2, PAICS were up regulated genes in CRC. It was also found that MMP3, THBS2, TIMP1 and CXCL12 genes were associated with metastatic CRC. Network analysis in ONCO.IO showed that upstream master regulators RELA, STAT3, SOX2, FOXM1, SMAD3 and NF-kB were connected with "core" hub-genes. CONCLUSION Results obtained are of useful fundamental information on revealing mechanism of pathogenicity, cellular targets selection for optimization of therapeutic interventions as well as transcriptomics prognostic and predictive biomarkers development.