Title:Transcriptomic Signatures in Colorectal Cancer Progression
Volume: 23
Issue: 3
Author(s): Pavel Ershov*, Stanislav Poyarkov, Yulia Konstantinova, Egor Veselovsky and Anna Makarova
Affiliation:
- Department of Analysis and Forecasting of Medical and Biological Health Risks, Federal State Budgetary
Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal
Medical Biological Agency, Moscow, Russia
Keywords:
Transcriptomics, hub-genes, colorectal cancer, networks, differential expression, prognostic value, protein-protein interactions.
Abstract:
Aims: Due to a large number of identified hub-genes encoding key molecular
regulators, which are involved 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 the 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 cancerassociated
pathways. Of them, there were two discrete clusters enriched in chemokine
signaling and cell cycle regulatory 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.
Conclusión: Results obtained are of useful fundamental information on revealing the
mechanism of pathogenicity, cellular target selection for optimization of therapeutic
interventions, as well as transcriptomics prognostic and predictive biomarkers
development.
