Multiomics Analysis of Tumor Microenvironment Reveals Gata2 and miRNA-124-3p as Potential Novel Biomarkers in Ovarian Cancer

Abstract

Ovarian cancer is a common and, yet, one of the most deadly human cancers due to its insidious onset and the current lack of robust early diagnostic tests. Tumors are complex tissues comprised of not only malignant cells but also genetically stable stromal cells. Understanding the molecular mechanisms behind epithelial-stromal crosstalk in ovarian cancer is a great challenge in particular. In the present study, we performed comparative analyses of transcriptome data from laser microdissected epithelial, stromal, and ovarian tumor tissues, and identified common and tissue-specific reporter biomolecules-genes, receptors, membrane proteins, transcription factors (TFs), microRNAs (miRNAs), and metabolites-by integration of transcriptome data with genome-scale biomolecular networks. Tissue-specific response maps included common differentially expressed genes (DEGs) and reporter biomolecules were reconstructed and topological analyses were performed. We found that CDK2, EP300, and SRC as receptor-related functions or membrane proteins; Ets1, Ar, Gata2, and Foxp3 as TFs; and miR-16-5p and miR-124-3p as putative biomarkers and warrant further validation research. In addition, we report in this study that Gata2 and miR-124-3p are potential novel reporter biomolecules for ovarian cancer. The study of tissue-specific reporter biomolecules in epithelial cells, stroma, and tumor tissues as exemplified in the present study offers promise in biomarker discovery and diagnostics innovation for common complex human diseases such as ovarian cancer.

Keywords: multiomics; network medicine; ovarian cancer; transcriptome; tumor microenvironment.