Association and discriminative performance of TNF-α and CA125 for disease severity and pain severity in endometriosis patients

Abstract

Endometriosis is a chronic inflammatory disease frequently associated with pelvic pain and disease progression. Tumor necrosis factor-alpha (TNF-α) and cancer antigen 125 (CA125) have been proposed as potential biomarkers reflecting inflammatory activity and disease burden. However, evidence remains limited on whether these biomarkers are associated with both anatomical disease severity and pain severity, particularly among patients with histopathologically confirmed endometriosis. The aim of this study was to evaluate the associations and discriminative performance of TNF-α and CA125 in relation to endometriosis severity and pain severity. A cross-sectional study was conducted at Dr. Zainoel Abidin Hospital, Banda Aceh, Indonesia, from October 2025 to January 2026, in which women with histopathologically confirmed endometriosis were included. Disease severity was classified intraoperatively using the revised American Society for Reproductive Medicine (rASRM) system. Pain severity was assessed using the Numeric Rating Scale (NRS). Peritoneal fluid TNF-α was measured using enzyme-linked immunosorbent assay (ELISA), and serum CA125 was measured using electrochemiluminescence immunoassay (ECLIA). Associations were analyzed using Spearman correlation, and discriminative ability was assessed using receiver operating characteristic (ROC) curve analysis. CA125 showed a significant positive correlation with rASRM stage (r=0.401; p=0.005) and TNF-α showed no significant correlation (r=0.068; p=0.649). ROC analysis demonstrated that CA125 had good discriminative ability for disease severity (AUC=0.808; p<0.001) with an optimal cut-off value of 32 U/mL. For pain severity, both CA125 (r=0.344; p=0.018) and TNF-α (r=0.338; p=0.020) had weak but significant positive correlations with NRS scores. ROC analysis indicated fair discriminative ability of CA125 (AUC=0.700; p=0.010) and TNF-α (AUC=0.674; p=0.031) for severe pain, with optimal cut-off values of 50.85 U/mL and 0.023 pg/mL, respectively. These findings highlight that CA125 is more consistently associated with endometriosis severity than TNF-α, while both biomarkers show limited ability to discriminate pain severity.