From Tumor Marker to Congestion Indicator: The Expanding Role of CA‐125 in Heart Failure and Beyond

Background and Aims: To evaluate the transition of Carbohydrate antigen 125 (CA-125) from an ovarian tumor marker to a versatile indicator of systemic congestion and fluid overload. Methods: A literature review (1984-2025) was conducted using PubMed, Scopus, and Web of Science. Keywords included "CA-125," "systemic congestion," and related terms. Studies on the diagnostic and prognostic value of CA-125 in congestive disorders were analyzed. Results: CA-125 is synthesized by mesothelial cells in response to mechanical stress and inflammation, particularly via c-Jun N-terminal kinase (JNK) signaling pathways. It provides significant prognostic value in heart failure (HF), renal failure, and cirrhosis, often rivaling or complementing NT-proBNP. Conclusion: CA-125 is a versatile biomarker for systemic congestion, offering diagnostic and prognostic value across cardiology, nephrology, and hepatology. Refining its clinical application could optimize fluid management in diverse patient populations.