Integration of Transcriptome and Epigenome to Identify and Develop Prognostic Markers for Ovarian Cancer

Abstract

DNA methylation is a widely researched epigenetic modification. It is associated with the occurrence and development of cancer and has helped evaluate patients’ prognoses. However, most existing DNA methylation prognosis models have not simultaneously considered the changes of the downstream transcriptome. Methods. The RNA-Sequencing data and DNA methylation omics data of ovarian cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Consensus Cluster Plus algorithm was used to construct the methylated molecular subtypes of the ovary. Lasso regression was employed to build a multi-gene signature. An independent data set was applied to verify the prognostic value of the signature. The Gene Set Variation Analysis (GSVA) was used to carry out the enrichment analysis of the pathways linked to the gene signature. The IMvigor 210 cohort was used to explore the predictive efficacy of the gene signature for immunotherapy response. Results. We distinguished ovarian cancer samples into two subtypes with different prognosis, based on the omics data of DNA methylation. Differentially expressed genes and enrichment analysis among subtypes indicated that DNA methylation was related to fatty acid metabolism and the extracellular matrix (ECM)-receptor. Furthermore, we constructed an 8-gene signature, which proved to be efficient and stable in predicting prognostics in ovarian cancer patients with different data sets and distinctive pathological characteristics. Finally, the 8-gene signature could predict patients’ responses to immunotherapy. The polymerase chain reaction experiment was further used to verify the expression of 8 genes. Conclusion. We analyzed the prognostic value of the related genes of methylation in ovarian cancer. The 8-gene signature predicted the prognosis and immunotherapy response of ovarian cancer patients well and is expected to be valuable in clinical application.

Application of natural polysaccharides and their novel dosage forms in gynecological cancers: therapeutic implications from the diversity potential of natural compounds

“…Its pathogenesis involves a wide range of molecular mechanisms and genetic modification, making it very difficult to treat ( Karnezis et al, 2017 ). Globally, due to the lack of the initial symptoms of ovarian cancer and the deficiency of screening methods, most of the patients have entered the advanced stage of the disease at the clinical diagnosis, and the 5-year survival rate is only 47% ( O'Connell et al, 2022 ; Xu and Cao, 2022 ). During the treatment of patients with advanced ovarian and recurrent ovarian cancer, the use of first-line chemotherapy, which is usually a combination of karplatinism or cispiene and paclitaxel compounds after tumor reduction, is the preferred plan for patients.…”