Identification of gene signatures and transcription factors associated with colorectal cancer through computational based approach

Abstract

Colorectal cancer (CRC), including colon and rectal cancer, is the most widespread malignant tumor worldwide. Besides, different staging groups in CRC complicate the diagnosis of disease conditions. This work explicates the idea of identifying the potential mRNA-miRNA-lncRNA as a prognostic signature for 4 stages of CRC. Datasets of GSE41011 (mRNA), GSE39833(miRNA) and GSE196006 (lncRNA) were chosen. In total, 62 mRNAs, 157 mRNAs as micro-RNA targets, and 101 mRNAs for lncRNAs were retrieved. Prominent genes were identified in stages I and II as RGMB, MND1, CBX2, GDPD5, DUSP15, SPC25 and SPP1. Genes specific for stages III and IV were RNF183, PRMT3, NOTCH3, CPNE7,GDPD5, DSCC1, KLHL35 and SPC25. Genes that play a role in all stages of CRC are PRMT3, SERPINB7, RORA, ARHGAP30, BUB1, CXCL3, EGR1, PXN, PTGES2-AS1, LINC03040 and hsa-miR-126, hsa-miR-1228.In addition, regulatory actions were also related to CRC progression. Moreover, we applied python weighted gene co-expression network analysis to further confirm the related gene expressions significantly altered in different stages of CRC. These correlated genes predicted 680,194 and 937 transcription factors (TFs) from mRNA, miRNA and lncRNA datasets. Subsequently, 17 TFs were revealed as a major interacting target with specific stages namely stage I - JUN, NR3C1, FOS, ESR1, GATA3; stage II - NANOG, GATA2; stage III - MYC, CEBPA, MYCN, POU5F1,SOX17, OTX2, MYB, TFAP2C, PBX1 and stage IV-TAL1.Taken to this factor, these findings will act as potent candidate gene signatures for therapeutic intervention at an early stage of CRC stage prediction.