Objective: This study aimed to explore the potential prognostic value and immunoregulatory roles of C-X-C motif chemokine ligand 10 (CXCL10) in ovarian cancer through bioinformatics analysis to identify potential biomarkers for personalized immunotherapy strategies.

Materials and Methods: We integrated Genotype-Tissue Expression (GTEx) normal ovarian tissues (n=88) and The Cancer Genome Atlas (TCGA) ovarian cancer samples (n=427) to screen differentially expressed genes using DESeq2 (version 1.42.0) and limma (version 3.40.2) packages. Protein-protein interaction networks (PPI) were constructed via Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape (version 3.10.1). Survival analysis was performed with Kaplan-Meier method and pathway enrichment was analyzed through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Immune infiltration was assessed using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. Validation was conducted using GEO datasets (GSE10971, GSE14407, GSE18520) and experimental verification through quantitative PCR (qPCR), Western blot, and Cell Counting Kit-8 (CCK-8) assays in ovarian cancer cell lines.

Results: CXCL10 expression was significantly upregulated in ovarian cancer tissues compared to normal tissues (p<0.001) and showed correlation with T-cell and macrophage infiltration (p<0.001). Patients with low CXCL10 expression had poor prognosis (HR < 1), while co-expression with immune checkpoint molecules programmed cell death protein 1 (PDCD1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and forkhead box P3 (FOXP3) was associated with longer survival. Functional enrichment analysis revealed that CXCL10 was significantly enriched in immune-related pathways including lymphocyte-mediated immune response and antigen presentation. Correlation analysis demonstrated strong associations between CXCL10 and immune checkpoint genes including PDCD1 and CTLA-4 (p<0.05). The time-dependent ROC analysis showed limited individual prognostic capability with AUC values of 0.446 for CXCL10, 0.478 for PDCD1, 0.435 for TIGIT, and 0.455 for FOXP3. Experimental validation confirmed that CXCL10 overexpression inhibited A2780 and SKOV3 cell proliferation (p<0.01) and enhanced the efficacy of anti-PD-1 antibodies.

Conclusions: Our findings suggest that CXCL10 may serve as a potential prognostic biomarker and immunotherapeutic target for ovarian cancer. The results indicate possible clinical applications in patient stratification and combination immunotherapy strategies, though further mechanistic studies and clinical validation are warranted.