Site-Specific Gene Expression Patterns Driving Liver and Lung Metastasis in Colorectal and Pancreatic Cancer

Metastasis, a critical phase in cancer progression, involves the dissemination of malignant cells to distant organs, significantly driving mortality. The hypothesis that genetic and molecular signatures regulate metastatic site selection underpins this study. Transcriptomic analyses of four common metastatic patterns, colorectal cancer (CRC) to lung or liver, and pancreatic cancer (PC) to these organs, were performed using GEO microarray datasets (GSE71729, GSE41258). Differentially expressed genes (DEGs) were identified by comparing metastatic and primary tissue profiles, excluding broadly shared metastatic genes to isolate site specific markers, and analyzed via Cytoscape with the MCC algorithm to determine 10 hub genes per site. Liver metastases in both CRC and PC shared nine hub genes: ALB, APOH, AHSG, APOA2, FGA, SERPINC1, FGB, HPX , and APOA1 , linked to cholesterol metabolism and coagulation, regulated by transcription factors (HNF4A, FOXA2, NR2F1), microRNAs (hsa-miR-124-3p, hsa-miR-182-5p), and lncRNAs (TUG1, NEAT1, XIST). Lung metastases across both cancers shared five hub genes: SFTPC, SFTPB, SCGE1A1, NKX2-1 , and ABCA3 , associated with ABC transporter and phagosome pathways, modulated by FOXA1, microRNAs (hsa-miR-15a-5p, hsa-miR-34a-5p, hsa-let-7b-5p), and lncRNAs (NEAT1, KCNQ1OT1). These consistent genetic and regulatory patterns provide strong evidence that genetic and molecular signatures determine metastatic site specificity, laying a foundation for targeted therapies.