Background: The coiled-coil domain-containing protein 80 (CCDC80) has known roles in signal transduction and as a structural protein that stabilizes the extracellular matrix (ECM). CCDC80 is also linked to drug resistance in cancers; however, the specific role of CCDC80 in platinum resistance in ovarian cancer (OC) remains unclear. This study used a variety of gene analysis and complementary experimental approaches to examine the prognostic significance of CCDC80 and the potential of this protein as a therapeutic target in OC. Methods: Differentially expressed genes (DEGs) were identified in the Gene Expression Omnibus (GEO) datasets (GSE15372, GSE51373, GSE114206) using the Limma package. The Kaplan-Meier analysis highlighted CCDC80 as a key gene. Weighted gene co-expression network analysis (WGCNA) identified a CCDC80-related module as being enriched in cell chemotaxis and ECM remodeling pathways. Quantitative reverse transcription polymerase chain reaction, Western blotting, and immunohistochemistry were used to confirm CCDC80 expression in platinum-resistant ovarian cancer (PROC) cell lines and clinical samples. Functional assays (cell count kit-8, colony formation, flow cytometry) were used to evaluate cisplatin sensitivity. Lastly, gene set enrichment analysis (GSEA), correlation analysis, and Western blotting were applied to investigate the mechanisms through which CCDC80 affected the platinum resistance of OC cells. Results: The Limma package and Kaplan-Meier analysis identified CCDC80 in the GEO datasets, and the WGCNA linked this protein to cell chemotaxis and ECM remodeling. The CCDC80 mRNA and protein expression levels were shown to be significantly higher in PROC cell lines and ovarian cancer tissue samples. Functional assays indicated that CCDC80 expression increases cisplatin resistance, while the GSEA and correlation analysis suggested that the epithelial–mesenchymal transition (EMT) pathway is a downstream target of CCDC80. Platinum resistance in OC cells was reduced by suppressing CCDC80 expression and increased by stimulating EMT, confirming the role of the CCDC80-EMT axis in platinum resistance. Conclusions: This study shows that CCDC80 expression is significantly elevated in platinum-resistant OC cells and that platinum resistance arises from CCDC-mediated activation of the EMT pathway. The CCDC80-EMT link provides a new understanding of the mechanisms leading to platinum resistance in OC and highlights CCDC80 as a possible therapeutic target to prevent the development of chemotherapy resistance.
Xu et al. (Fri,) studied this question.