Identification of FGF۱۹ and CTNNA۲ as Novel Dual-Gene Signatures for Early and Late-Onset Colorectal Cancer Diagnosis: A Systems Biology Approach

Introduction Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide. While the majority of CRC cases are detected in older individuals, the incidence of early-onset colorectal cancer (EOCRC), appearing in the age<۵۰ years old, steadily has been rising worldwide and its causes are incompletely defined. Understanding the differential expression profiles between EOCRC and late-onset colorectal cancer (LOCRC) may provide critical insights into their biological behavior and report age-specific therapeutic strategies. Therefore, this study aimed to investigate the differential expression of genes (DEGs) between EOCRC and LOCRC to identify unique gene-expression signatures that may underlie the distinct biological behaviors of these two groups. Methods Based on a systems biology approach, RNA-seq data was extracted from the GEO under accession number GSE۲۱۳۰۹۲ and TCGA-COAD dataset to identify DEGs between EOCRC and LOCRC. Then, the co-expression network of DEGs associated with CRC and their target genes was constructed using the weighted gene co-expression network analysis (WGCNA) algorithm. Finally, pathway enrichment analysis clarified their roles in biological processes and molecular pathways driving CRC in different age groups. Results The intersection of genes between WGCNA and DEG showed that significant upregulated FGF۱۹ and CTNNA۲ are hub genes of ECOCRC. These findings indicated that the genes were mostly enriched in the signaling pathways involved in carcinogenesis such as Hippo, RAS, and MAPK. Therefore, novel dual-gene signatures (FGF۱۹, CTNNA۲) were identified as a potential predictor in developing colorectal cancer at a young age that can classify patients into ECOCRC and LOCRC groups. Conclusion The systems biology approach indicated distinct gene expression profiles between EOCRC and LOCRC, highlighting novel dual-gene signatures that may assist in the differences in CRC onset by age. Also, this gene co-expression network offers new insights into the pathogenesis of CRC. It may inform the development of targeted therapies and diagnostic tools for early and late-onset colorectal cancer.

کلیدواژه ها:

Early-onset colorectal cancer ، Later-onset colorectal cancer ، Systems biology ، Gene-expression signatures