Identification of a Recurrence Gene Signature for Ovarian Cancer Prognosis by Integrating Single-Cell RNA Sequencing and Bulk Expression Datasets

Abstract

Ovarian cancer is one of the most common gynecological malignancies in women, with a poor prognosis and high mortality. With the expansion of single-cell RNA sequencing technologies, the inner biological mechanism involved in tumor recurrence should be explored at the single-cell level, and novel prognostic signatures derived from recurrence events were urgently identified. In this study, we identified recurrence-related genes for ovarian cancer by integrating two Gene Expression Omnibus datasets, including an ovarian cancer single-cell RNA sequencing dataset (GSE146026) and a bulk expression dataset (GSE44104). Based on these recurrence genes, we further utilized the merged expression dataset containing a total of 524 ovarian cancer samples to identify prognostic signatures and constructed a 13-gene risk model, named RMGS (recurrence marker gene signature). Based on the RMGS score, the samples were stratified into high-risk and low-risk groups, and these two groups displayed significant survival difference in two independent validation cohorts including The Cancer Genome Atlas (TCGA). Also, the RMGS score remained significantly independent in multivariate analysis after adjusting for clinical factors, including the tumor grade and stage. Furthermore, there existed close associations between the RMGS score and immune characterizations, including checkpoint inhibition, EMT signature, and T-cell infiltration. Finally, the associations between RMGS scores and molecular subtypes revealed that samples with mesenchymal subtypes displayed higher RMGS scores. In the meanwhile, the genomics characterization from these two risk groups was also identified. In conclusion, the recurrence-related RMGS model we identified could provide a new understanding of ovarian cancer prognosis at the single-cell level and offer a reference for therapy decisions for patient treatment.