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

ABSTRACT 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.