Bioinformatics-driven discovery and experimental validation of differentially expressed genes in colorectal adenomas

Colorectal cancer (CRC) progression from benign polyps to malignant adenocarcinomas is a complex process involving the abnormal proliferation and differentiation of colon epithelial cells. Colorectal adenomas (CRAs), the precursors to most CRCs, are histologically classified into tubular adenomas (TAs), tubulovillous adenomas (TVAs), and villous adenomas (VAs). Despite new findings, the molecular signatures and pathways specific to each adenoma type remain poorly understood. This study aimed to identify specific biomarkers and pathways associated with the progression of TA, TVA, and VA to CRC.

We analyzed gene expression data from 169 CRA samples and 65 adjacent normal tissues from the GSE117606 and GSE117607 datasets. Differentially expressed genes (DEGs) were identified for each adenoma type, followed by functional enrichment and protein-protein interaction network analysis. Our results revealed 1,024 DEGs common to all three adenoma types, with COL1A2 and CXCL8 highlighted as hub genes. Additionally, specific genes such as NTRK2, JUN, LAT, and DRD2 were identified for TA; H2AFZ, NME1, MRTO4, and SSRP1 were identified for TVA; and WDR43, POLR1B, and NHP2 were identified for VA. Functional enrichment analysis revealed key pathways involved in adenoma progression, providing insights into the molecular mechanisms driving their malignancy potential. The expression of candidate genes was further validated by RT-qPCR, and repeated cross-validated ROC analysis supported the discriminative potential of CXCL8 and COL1A2 for distinguishing CRA and CRC tissues from adjacent normal mucosa.

These findings provide valuable insights into adenoma biology and offer potential applications for targeted therapies in CRC prevention and treatment.