Transcriptome-based Stemness Indices Analysis Reveals Platinum-based Chemotheraputic Response Indicators in Advanced-stage Serous Ovarian Cancer

Abstract Background: Serous ovarian cancer (SOC) is a main histological subtype of ovarian cancer (OC). Cancer stem cells (CSCs), with self-renewal and differentiation potential, are considered to be the cause of chemoresistance in SOC. However, the underlying modulation mechanisms of chemoresistance led by cancer stemness are still undefined. Results: We found that mRNAsi and corrected mRNAsi (by tumor purity) scores were both greater in tumors of Grade 3 and 4 than that of Grade 1 and 2, indicating a stronger stemness in cancer cells of higher grades. A total of 42 key genes were obtained from the most significant mRNAsi-related gene module. Functional annotation revealed that these key genes were mainly involved in mitotic division and were closely related to cell proliferation. A total of 13 potential platinum response indicators were selected from the genes enriched to platinum-response associated pathways. Among the 13 key genes, we identified 11 genes with prognostic value of progression-free survival (PFS) in advanced-stage SOC patients treated with chemotherapy containing platinum and 7 prognostic genes in patients treated with the combination of platinum and taxol. The expression of the 13 key genes was also validated between platinum-resistant and sensitive SOC samples of advanced stages in two Gene Expression Omnibus (GEO) datasets. Conclusion: The results revealed that CDC20 was a potential platinum-based chemotherapeutic response indicator in advanced-stage SOC and the findings may provide new insight into the prediction of drug response thus to guiding the use of chemotherapies in patients of advanced-stage SOC in the clinic.