Transcriptomic Signatures in Colorectal Cancer Progression

Abstract

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.

Identification of GUCA2A and COL3A1 as prognostic biomarkers in colorectal cancer by integrating analysis of RNA-Seq data and qRT-PCR validation

“…Liu et al 77 used analysis of the TCGA database revealed that the expression of GUCA2A and GUCA2B was significantly downregulated in CRC tissues, which is consistent with our results. As reported by Ershov et al 78 the expression of GUCA2A was considerably downregulated in CRC tissues, which is consistent with our findings. According to Xu et al 79 , GUCA2A expression level in colorectal cancer tissues were lower than in healthy tissues, which is consistent with the experimental findings from our investigations.…”

Collagen Family as Promising Biomarkers and Therapeutic Targets in Cancer

“…In the remodeling steps during tumor growth, the normal ECM collagens are substituted with a tumor-specific collagen profile [ 70 ]. Increased expression of different collagens was associated with tumor progression and a poor prognosis in various types of epithelial cancers including colorectal [ 71 ], esophagus [ 72 ], glioma [ 73 ], gastric [ 74 , 75 ], head and neck [ 76 ], lung [ 77 ], ovarian [ 78 ], pancreatic [ 79 ], renal [ 80 ], breast [ 81 , 82 ], and cervical cancer [ 83 ]. The profile of different collagen types expressed in various solid cancers is presented as a heatmap in Figure 2 .…”

Identification of shared molecular mechanisms and diagnostic biomarkers between heart failure and idiopathic pulmonary fibrosis

“…This protein is present in many fibrotic illnesses included multiple organs, such as heart, lung fibrosis, kidney and liver [ [25] , [26] , [27] ]. Collagen III contributes to cell adhesion, motility, and differentiation through its interaction with integrins [ 28 ] THBS2 is associated with metastatic colorectal cancer, is shown to be expressed at higher levels in lung cancer, and participates in focal adhesion signalling pathways [ [29] , [30] ]. CCND1 gene regulates cell cycle progression and its upregulation promotes the development of various tumours.…”