Combined prognostic utility of serum CA-125, HE4, and hormonal receptor expression in predicting tumor aggressiveness and clinical outcome in advanced cervical cancer
Abstract
Advanced cervical cancer remains a major cause of cancer-related morbidity and mortality among women worl d wide. Reliable biomarkers capable of predicting tumor aggressiveness and clinical outcome are needed to improve risk stratification and therapeutic decision-making. Serum tumor markers and hormonal receptor expression may provide valuable prognostic information regarding disease progression and metastatic potential. The objective of the present study was t o evaluate the combined prognostic utility of serum CA-125, HE4, and hormonal receptor (ER and PR) expression in predicting tumor aggressiveness, disease stage, metastatic behavior, and clinical outcome in patients with advanced cervical cancer. A case –control study was conducted between July 2025 and April 2026 involving 150 wo m en with FIGO stage III–IV cervical cancer and 50 healthy controls. Serum CA-125, HE4, and SCC-Ag levels were measured using ELISA. Estrogen receptor (ER) and progesterone receptor (PR) expression were assessed by immun o histochemistry in cervical tissue specimens. Associations between biomarkers, FIGO stage, metastatic status, and clinicopathological characteristics were statistically analyzed. The p atients with advanced cervical cancer exhibited significantly higher serum CA-125, HE4, and SCC-Ag levels than the controls. Tumor marker concentrations were significantly elevated in stage IV compared with stage III disease and in the metastatic compared with non metastatic patients. The positivity of ER and PR w as significantly lower among metastatic cases. HE4 demonstrated the strongest correlation with FIGO stage (r = 0.511) and metastatic status (r = 0.486), while the combined CA-125 + HE4 score showed the highest overall correlations with FIGO stage (r = 0.548) and metastasis (r = 0.503). Serum CA-125 and HE4, particularly when combined, are valuable indicators of tumor aggressiveness and metastatic potential in advanced cervical cancer. Reduced ER and PR expression is associated with unfavorable clinicopathological features. Integrating serum tumor markers with hormonal receptor status may enhance prognostic assessment and facilitate personalized management strategies for patients with advanced cervical cancer.References
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