Prolactin and CA-125 Crosstalk: A Narrative Review of Hormonal Influence in Ovarian Cancer

Abstract

Ovarian cancer (OC) is the most lethal gynecological malignancy, largely due to its asymptomatic progression and lack of reliable early diagnostic tools. The established biomarker CA-125 remains limited by inadequate sensitivity and specificity, particularly in early-stage disease, underscoring the urgent need for complementary biomarkers and multimodal diagnostic strategies. Prolactin (PRL), a pleiotropic hormone with demonstrated onco-modulatory roles in various cancers, has emerged as a potential candidate to enhance OC detection and prognosis. This narrative review synthesizes current evidence on the crosstalk between prolactin and CA-125 and evaluates their combined utility in ovarian cancer diagnosis and risk stratification.

Through a systematic analysis of existing literature, this thesis addresses key research gaps: the inconsistent evidence regarding prolactin’s diagnostic value, the underexplored biological interaction between prolactin and CA-125, and the absence of a validated multimodal model integrating these biomarkers with transvaginal ultrasound (TVS). The review highlights that while some studies report elevated prolactin levels in OC and correlate them with tumor aggressiveness and poor survival, others show no significant association, partly due to pre-analytical variability and heterogeneous study designs. Evidence suggests that prolactin may enhance diagnostic accuracy when combined with CA-125, as demonstrated in biomarker panels such as MIF-OPN-PROL-CA125, which have shown superior performance over CA-125 alone.

Mechanistically, prolactin exerts pro-tumorigenic effects in OC through signaling pathways such as JAK/STAT, MAPK/ERK, and PI3K/Akt/mTOR, which overlap with pathways influencing CA-125 expression and tumor progression. This crosstalk suggests potential synergistic roles in disease pathogenesis. Furthermore, integrating prolactin and CA-125 with TVS could offer a more robust, multi-parameter approach to improving early detection, especially in high-risk populations.

In conclusion, this review advocates for the development and clinical validation of an integrated diagnostic framework incorporating prolactin, CA-125, and imaging to improve early detection, prognostic assessment, and personalized management of ovarian cancer. Future research should focus on standardized biomarker measurement, prospective validation of combined panels, and exploration of the molecular interplay between prolactin and CA-125 in OC pathogenesis.