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.

Identification of Prognostic Biomarker Signatures and Candidate Drugs in Colorectal Cancer: Insights from Systems Biology Analysis

“…The high-throughput gene expression profiling technology has been considered as one of the efficient sources for screenening of biomarker candidates [7][8][9]. Understanding the disease pathways and exploration of biomarkers requires integration of omics data from different levels, and the power of this multi-omics approach in elucidation of molecular signatures in human diseases was previously shown in many human diseases [14][15][16][17][18][19][20][21][22]. Consequently, we employed a system biomedicine approach to explore the in-depth mechanism of CRC in the present study.. ,…”

“…The power of multi-omics analyses within network biomedicine perspective [14] in elucidation of molecular signatures in human diseases was previously shown in many human diseases such as head and neck cancers [15], esophageal squamous cell carcinoma [16], triple negative breast cancer [17], cervical cancer [18], ovarian cancer [19] and ovarian diseases [20], psoriasis [21] and type 2 diabetes [22]. Therefore, in this study, systems-based approaches have been considered to explore the potential biomarker signatures at protein (i.e., hub proteins and TFs) and RNA levels (i.e., miRNAs and mRNAs) ( Figure 1).…”

MicroRNA-124-3p Functions as a Marker in Diagnosing Breast Cancer

“…They are unsatisfactory for screening of breast cancer. Recently, miR-124-3p was reported to be generally reduced in multiple tumors while its transfection suppresses the malignant cellular growth and migration [22][23][24][25]. For example, Gov E et al reported that miR-124-3p was a plausible indicator in ovarian cancer [22].…”

Genetic Susceptibility for Cervical Cancer in African Populations: What Are the Host Genetic Drivers?

“…Cancer is caused by both genetic and environmental factors (Gov et al, 2017). Successful management of cancer could benefit from identifying polymorphisms that play a role in gene expression and cell cycle regulation as well as genome-environment interactions (Advani et al, 2017).…”