Two microRNA Signatures for Malignancy and Immune Infiltration Predict Overall Survival in Advanced Epithelial Ovarian Cancer

MicroRNAs have been established as key regulators of tumor gene expression and as prime biomarker candidates for clinical phenotypes in epithelial ovarian cancer (EOC). We analyzed the coexpression and regulatory structure of microRNAs and their colocalized gene targets in primary tumor tissue of 20 advanced epithelial ovarian cancer patients in order to construct a regulatory signature for clinical prognosis. We performed an integrative analysis to identify two prognostic microRNA/mRNA coexpression modules, each enriched for consistent biological functions. One module, enriched for malignancy related functions, was found to be upregulated in malignant versus benign samples. The second module, enriched for immune related functions, was strongly correlated with intratumoral immune infiltrates of T cells, NK cells, Cytotoxic Lymphocytes, and Macrophages. We validated the prognostic relevance of the immunological module microRNAs in the publically available TCGA dataset. These findings provide novel functional roles for microRNAs in the progression of advanced EOC and possible prognostic signatures for survival. 26 samples from Primary EOC tumor and 13 samples from benign Ovarian masses were assayed.