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Clinical and Experimental Immunology | sB7-H4 as a Diagnostic Biomarker for Epithelial Ovarian Cancer and Its Correlation with Platinum Resistance

Clinical and Experimental Immunology | sB7-H4 as a Diagnostic Biomarker for Epithelial Ovarian Cancer and Its Correlation with Platinum Resistance
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This study systematically evaluated sB7-H4 concentrations in plasma and ascites of patients with epithelial ovarian cancer (EOC) and analyzed their correlation with clinical parameters such as FIGO stage, histological subtype, surgical resection status, and platinum resistance. Results demonstrate that sB7-H4 serves as a potential biomarker for EOC, with enhanced diagnostic accuracy when combined with CA125 and HE4. It also provides predictive insights for platinum resistance.

 

Literature Overview
The article 'sB7-H4 is a diagnostic biomarker in epithelial ovarian cancer and correlates to platinum resistance' published in *Clinical and Experimental Immunology* reviews sB7-H4 expression in plasma and ascites of ovarian cancer patients, emphasizing its association with disease staging, surgical outcomes, lymphatic metastasis, and platinum resistance. Using ELISA, immunohistochemistry, and multiplex immunofluorescence, the study systematically analyzed the positive correlation between sB7-H4 expression in EOC tissues and plasma levels, highlighting its potential in diagnosis and prognosis.

Background Knowledge
Epithelial ovarian cancer (EOC) is a leading cause of mortality among gynecological malignancies, with ~70% of patients presenting at advanced stages due to asymptomatic early phases and limited effective biomarkers. As an immune-regulatory protein in the B7 family, B7-H4 suppresses T cell activation, facilitating tumor immune evasion. It is overexpressed in multiple cancers and linked to poor prognosis. In ovarian cancer, B7-H4 is associated with treatment resistance, immune microenvironment remodeling, and tumor progression. This study focuses on soluble sB7-H4 expression in EOC, exploring its utility as a non-invasive biomarker for platinum resistance and surgical evaluation. It addresses the current clinical gap in systemic sB7-H4 analysis, providing theoretical foundations for personalized therapy and immunotherapy target development.

 

 

Research Methods and Experiments
The study enrolled 55 EOC patients diagnosed at the First Affiliated Hospital of Soochow University between January 2022 and January 2023, alongside non-EOC controls (22 borderline ovarian tumors and 54 benign ovarian epithelial tumors). A healthy control group (n=43) was recruited from the health check-up center. Venous blood, intraoperative ascites, and primary tumor tissues were collected. sB7-H4 concentrations were measured by ELISA, while tissue expression and cellular localization were analyzed via immunohistochemistry and multiplex immunofluorescence. Statistical analyses were performed using GraphPad Prism 9 and SPSS 25.0 to evaluate correlations between sB7-H4 and clinical indicators (e.g., stage, lymphatic metastasis, platinum resistance), with diagnostic performance assessed via ROC curves.

Key Conclusions and Perspectives

  • sB7-H4 levels in EOC patients' plasma were significantly higher than in healthy controls, benign tumors, and borderline tumors, with ROC analysis showing an AUC of 0.893, sensitivity of 76.4%, and specificity of 92% for EOC diagnosis.
  • sB7-H4 concentrations were elevated in advanced-stage EOC, high-grade serous ovarian cancer (HGSOC), lymphatic metastasis, and postoperative residual disease, indicating strong associations with disease progression and treatment resistance.
  • Ascites sB7-H4 levels exceeded plasma levels and positively correlated with tissue expression, suggesting localized tumor release followed by systemic circulation impact on the immune microenvironment.
  • Combining sB7-H4 with traditional biomarkers CA125 and HE4 significantly improved diagnostic efficacy, particularly for predicting platinum resistance and lymphatic metastasis.
  • sB7-H4 levels decreased after surgery/chemotherapy but rose sharply in recurrence cases, demonstrating its value as a monitoring indicator for treatment response.

Research Significance and Prospects
This study pioneers the systemic analysis of sB7-H4 expression in EOC and its correlation with platinum resistance and surgical outcomes, introducing a novel non-invasive biomarker for clinical use. Future work should validate findings through larger cohorts and mechanistic studies to explore its applications in immunotherapy and targeted treatments.

 

 

Conclusion
This study systematically evaluated sB7-H4 expression in epithelial ovarian cancer and its relationship with clinical features, revealing significantly elevated levels in EOC patients' plasma and ascites, particularly in advanced stages, lymphatic metastasis, and platinum-resistant cases. sB7-H4 demonstrates potential as an independent biomarker for early diagnosis, staging, and treatment monitoring of EOC. When combined with CA125 and HE4, its diagnostic sensitivity and specificity improve further, providing theoretical support for precision medicine. Future B7-H4-targeted immunotherapy may offer new strategies to reverse EOC drug resistance.

 

Reference:
Ying Zhou, Jingluan Tian, Yu Shen, Juan Wang, and Yanzheng Gu. sB7-H4 is a diagnostic biomarker in epithelial ovarian cancer and correlates to platinum resistance. Clinical and Experimental Immunology.