Prognostic and Immunotherapeutic Potential of Regulatory T Cell- Associated Signature in Ovarian Cancer

Abstract Background: Immunosuppression is a key feature of cancer, promoting tumor growth and progression. Regulatory T cells (Tregs) are a specialized subset of T lymphocytes that mediate immunosuppression in cancer. However, the role of Treg-related genes in ovarian cancer (OC) remains largely unexplored. Methods: To identify marker genes related to Tregs in OC, we utilized scRNA-seq analysis. Treg scores were then constructed using single-sample gene set enrichment analysis (ssGSEA) based on these markers. To identify gene modules with the strongest correlation with Treg scores in bulk RNA-seq data, we employed the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm. Multiple machine learning algorithms were then used to construct risk models with superior predictive performance, which were validated using external independent datasets. A risk score was developed for each OC sample based on the optimal model to evaluate differences in prognosis, immune infiltration, pathway activity, and immunotherapy between high and low-risk groups. Results: We identified 365 genes governing Treg functionality utilizing the WGCNA algorithm, and determined that 70 of these genes were linked to the prognosis of OC based on univariate Cox analysis. By employing a fusion of the Random Survival Forest (RSF) and Lasso algorithms, we developed a risk model showcasing the most elevated c-index derived from the allocated risk scores. The model's efficacy was substantiated through the utilization of four external datasets. Our analysis unveiled that the low-risk cohort exhibited a more favorable prognosis, augmented infiltration of immune cells, elevated expression of immune checkpoints, as well as noteworthy disparities in pathway enrichment and immunotherapy efficacy among the distinct risk groups. Conclusion: Our findings provide new insights into the role of Treg cells in the development and progression of OC and highlight the potential for developing novel Treg-targeted therapies for the treatment of this disease.