Identification of an Immune Gene-Based Cisplatin Response Model and CD27 as a Therapeutic Target against Cisplatin Resistance for Ovarian Cancer

Abstract

Objective. Evidence demonstrates that the immune microenvironment is extensively associated with chemotherapy response of ovarian cancer (OV). Herein, this study is aimed at establishing a cisplatin response prediction model for OV on the basis of immune genes. Methods. The expression profiles of cisplatin-sensitive and cisplatin-resistant OV specimens were integrated from multiple public datasets. The abundance scores of 22 immune cells were estimated with CIBERSORT algorithm. Differentially expressed immune genes (DEGs) were determined between cisplatin-sensitive and cisplatin-resistant groups. Thereafter, a cisplatin response model was constructed based on prognostic DEGs with logistic regression analysis. The prediction performance was validated in independent cohorts. The possible relationships between the model and immunotherapy were then assessed. Results. Treg scores were significantly decreased in cisplatin-resistant than cisplatin-sensitive OV specimens, with the opposite results for naïve B cells and activated dendritic cells. Fourteen prognostic DEGs were identified and used to develop a cisplatin-response model. The response scores, estimated by the model, showed favorable performance in discriminating cisplatin-response and nonresponse samples. The response scores also presented significantly negative correlations with three well-known cisplatin-resistant pathways and a positive correlation with the expression of CD274 (PD-L1). Moreover, the decreased CD27 expression was observed in cisplatin-resistant groups, and OV specimens with higher CD27 expressions were more sensitive to cisplatin treatment. Conclusion. Altogether, our findings proposed a cisplatin response prediction model and identified CD27 that might be involved in cisplatin resistance. Further investigations suggested that CD27 could be a promising immunotherapeutic target for cisplatin-resistant subset of OV.