Identification of hub genes and pathways in colitis-associated colon cancer by integrated bioinformatic analysis

Abstract

Background: Colitis-associated colon cancer (CAC) patients have a younger age of onset, more multiple lesions and invasive tumors than sporadic colon cancer patients. Early detection of CAC using endoscopy is challenging, and the incidence of septal colon cancer remains high. Therefore, identifying biomarkers that can predict the tumorigenesis of CAC is in urgent need. Results: A total of 275 DEGs were identified in CAC. IGF1, BMP4, SPP1, APOB, CCND1, CD44, PTGS2, CFTR, BMP2, KLF4, and TLR2 were identified as hub DEGs, which were significantly enriched in the PI3K-Akt pathway, stem cell pluripotency regulation, focal adhesion, Hippo signaling, and AMPK signaling pathways. Sankey diagram showed that the genes of both the PI3K-AKT signaling and focal adhesion pathways were upregulated (e.g., SPP1, CD44, TLR2, CCND1, and IGF1), and upregulated genes were predicted to be regulated by the crucial miRNAs: hsa-mir-16-5p, hsa-mir-1-3p, et al. Hub gene-TFs network revealed FOXC1 as a core transcription factor. In ulcerative colitis (UC) patients, KLF4, CFTR, BMP2, TLR2 showed significantly lower expression in UC-associated cancer. BMP4 and IGF1 showed higher expression in UC-Ca compared to nonneoplastic mucosa. Survival analysis showed that the differential expression of SPP1, CFRT, and KLF4 were associated with poor prognosis in colon cancer. Conclusion: Our study provides novel insights into the mechanism underlying the development of CAC. The hub genes and signaling pathways may contribute to the prevention, diagnosis and treatment of CAC.