Differential diagnosis of benign and malignant ovarian tumors with combined tumor and systemic inflammation-related markers

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Abstract

Background: To explore the diagnostic significance of pre-surgery peripheral blood tumor markers cancer antigen 125 (CA125) and human epitope protein 4 (HE4), in conjunction with neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet count-to-lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII), in the differential diagnosis of epithelial ovarian cancer (EOC) and benign ovarian tumors. Determine the best combination of diagnostic indicators for early diagnosis of EOC. Methods: We retrospectively analyzed clinical data from 189 patients with EOC and 202 patients with benign ovarian tumors, comparing levels of CA125, HE4, and inflammatory markers, and evaluated the efficacy of these markers in diagnosing EOC alone or in combination by calculating sensitivity, specificity, and receiver operating characteristic curve (ROC). Results: Serum concentrations of CA125, HE4, NLR, PLR, MLR, and SII were significantly higher in the EOC group than in the benign ovarian tumor group (P < 0.001). In 189 cases of EOC, CA125 and HE4 were significantly higher in advanced stages than in early stages (P = 0.000, P = 0.012). NLR, PLR, MLR, and SII showed no significant difference between early and advanced stages (P>0.05), and this was also the case in 141 patients with high-grade serous ovarian cancer. CA125, HE4, NLR, PLR, MLR, and SII showed no significant differences across age groups, menopausal states, or pathological types (P > 0.05 for all). For diagnosing EOC, both the CA125+HE4+NLR+PLR+MLR+SII and CA125+HE4+PLR+MLR+SII models achieved the highest AUC values (AUC = 0.951 for both). No statistically significant difference was observed between these two models in AUC comparison (P=0.9305). NLR alone showed the lowest AUC at 0.696. The CA125+HE4+PLR+MLR+SII model demonstrated the highest sensitivity (84.66%), while CA125+HE4 showed the highest specificity (95.54%). Conclusion: Preoperative peripheral blood tumor markers combined with inflammatory markers can improve the diagnostic efficiency of EOC. Among these combinations, CA125+HE4+PLR+MLR+SII demonstrated optimal diagnostic performance with the highest efficacy and sensitivity, providing a clinical basis for enhanced EOC diagnosis.

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Song, D., Liu, T., Han, C., Zhang, C., & Kong, W. (2025). Differential diagnosis of benign and malignant ovarian tumors with combined tumor and systemic inflammation-related markers. Journal of Cancer, 16(10), 3192–3201. https://doi.org/10.7150/jca.112768

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