m6A-Related lncRNA Signature Is Involved in Immunosuppression and Predicts the Patient Prognosis of the Age-Associated Ovarian Cancer

Abstract

Background. Epithelial ovarian cancers are age-associated diseases, usually diagnosed at an advanced stage. lncRNA has been discovered to interplay with N6-methyladenosine (m6A), working in tandem to promote cancer progression and worsening patient outcomes. This study is aimed at investigating the roles and mechanism of m6A-related lncRNA signature on ovarian cancers. Methods. We retrieved TCGA and CGGA sequencing data to identify m6A-related lncRNA signature and constructed an m6A score (MS) using the LASSO algorithm. A clinical nomogram was then established to predict the overall survival of patients. Subsequently, GSEA analyses were conducted to obtain pathways involved. Expression of HLA genes, 28 tumor-infiltrating lymphocyte infiltration, and anticancer cycle were analyzed the immunological differences between high-MS and low-MS groups. Finally, immune checkpoint gene expressions and IC50 of chemotherapeutic drugs were calculated, and CMap was run to identify the potential compounds and their corresponding mechanisms. Results. We identified 16 m6A-related lncRNAs and constructed an MS model. The high-MS group showed a poor prognosis. A clinical nomogram consists of MS, and age was constructed and predicted the 1-, 3-, and 5-year survival with high accuracy. GSEA analyses presented downregulated antigen processing and presentation pathways. Immunocyte infiltrating analyses demonstrated that high-MS was associated with high infiltration of Treg cells, macrophages, and low Th1/Th2 rate. Also, high expression of immune checkpoint genes NRP1, TNFSF9, and VSIR was observed in the high-MS group. Finally, the high-MS group also predicted low IC50 of vinorelbine and vorinostat. Conclusion. This study constructed a robust prediction model for prognostic management and revealed the cross-talk between m6A and immunosuppression. Besides, the m6A lncRNA signature can predict the chemotherapeutic drug response. These will shed light on the development of novel therapeutic strategies and render survival benefits for ovarian patients.