Ovarian cancer-specific dysregulated genes with prognostic significance: scRNA-Seq with bulk RNA-Seq data and experimental validation.

Abstract

A major cause of gynecological cancer -related deaths worldwide, ovarian cancer is characterized by heterogeneity in both tumor cells and the tumor microenvironment (TME). Our study aimed to characterize tumor cell heterogeneity and the infiltration of M2 tumor-associated macrophages (TAMs) in the ovarian cancer TME by single-cell RNA-Seq (scRNA-Seq) analysis combined with bulk RNA sequencing (bulk RNA-Seq). Several highly variable genes were identified in ovarian cancer tissues, and tumor cell heterogeneity and infiltrating immune tumor cell heterogeneity were characterized in ovarian cancer cells. M2 TAMs in the TME were the predominant phenotype of TAM. Further, M2 TAM infiltration in the TME was negatively correlated with poor prognosis of ovarian cancer patients. Four M2 TAM-associated genes (SLAMF7, GNAS, TBX2-AS1, and LYPD6) correlated with the prognostic survival of ovarian cancer patients. Knockdown of SLAMF7 or GNAS mRNA repressed malignancy and cisplatin resistance of ovarian cancer cells. ScRNA-Seq combined with bulk RNA-Seq identified the same four genes associated with M2 TAMs. The prognostic risk score model based on these four genes may hold favorable predictive value for the prognosis of ovarian cancer patients.