CLIP2 is a potential biomarker for platinum resistance and prognosis in ovarian cancer: a bioinformatics analysis.

BACKGROUND

Ovarian cancer exhibits the highest mortality rate among gynecologic malignancies. Platinum resistance remains a key determinant of poor clinical outcomes. Early prediction of platinum resistance is critical for personalized treatment. This study aimed to identify CLIP2 as an independent prognostic biomarker and assess its predictive value for platinum resistance and the tumor immune microenvironment in ovarian cancer.

METHODS

Through integrated bioinformatics analysis of ovarian cancer cohorts from TCGA and GEO, we performed differential gene expression profiling, survival analysis, and multivariate Cox regression to identify biomarkers associated with platinum resistance and prognosis. A CLIP2-based logistic regression model was constructed and evaluated using leave-one-out cross-validation (LOOCV). TCGA patients were stratified by CLIP2 expression for comparative analyses of overall survival, mutational landscapes, drug sensitivity, and immunogenomic characteristics.

RESULTS

CLIP2 was identified as an independent predictor of platinum resistance and a significant prognostic biomarker (HR = 1.20; 95% CI: 1.05-1.40; p = 0.007). The CLIP2-based model achieved an AUC of 0.68. The high-CLIP2 subgroup exhibited significantly poorer overall survival (log-rank p = 0.04) and distinct somatic mutation profiles. Drug sensitivity analysis revealed that high CLIP2 expression conferred resistance to platinum-based agents, topotecan, and gemcitabine, but heightened sensitivity to olaparib, cediranib, and pictilisib. Immunogenomic profiling further indicated that CLIP2 overexpression was associated with an immunosuppressive microenvironment, characterized by depleted infiltration of activated dendritic cells, CD8⁺ T cells, M1 macrophages, and helper T cells, alongside positive correlations with inhibitory checkpoints (CD276, ADORA2A, and ENTPD1) and negative correlations with stimulatory checkpoints (CD48 and NCR3).

CONCLUSIONS

Through bioinformatic analysis, this study proposes CLIP2 as a potential biomarker associated with platinum resistance and immune microenvironment patterns in ovarian cancer. These preliminary findings provide a basis for subsequent mechanistic studies and larger validation cohorts to confirm its clinical relevance in guiding immunotherapy and targeted treatment approaches.