Abstract Background: Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Identifying novel biomarkers is critical for improving diagnosis, prognosis, and treatment strategies. This study investigates the serum levels of kisspeptin-1 (KISS1), its receptor (KISS1R), growth differentiation factor 15 (GDF15), and carcinoembryonic antigen (CEA) in Iraqi CRC patients. Objectives: Explore associations between serum levels of Kiss1, Kiss1R, GDF, and CEA and disease progression in Iraqi patients with CRC. Methods: A case-control study was conducted, including 72 CRC patients and 36 healthy controls. Patients were stratified into non-metastatic and metastatic groups. Serum biomarker levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses evaluated biomarker correlations, diagnostic accuracy, and associations with CRC stages. Results: Significant elevations of KISS1, KISS1R, GDF15, and CEA levels were observed in CRC patients compared to controls, with metastatic cases showing the highest levels. KISS1 and GDF15 demonstrated strong correlations and were particularly associated with metastatic disease. Receiver operating characteristic (ROC) analysis revealed high diagnostic accuracy for these biomarkers in distinguishing CRC stages. Conclusions: KISS1 and GDF15 are promising biomarkers for CRC progression and metastasis. Their coordinated elevation in metastatic cases suggests potential roles in disease monitoring and therapeutic targeting. Further studies are needed to confirm these findings and explore their clinical applications.
