An integrated network of microRNA and gene expression in ovarian cancer

Ovarian cancer is a deadly female reproductive cancer. Understanding the biological mechanisms underlying ovarian cancer could help lead to quicker and more accurate diagnosis and more effective treatments. Both changes in microRNA(miRNA) expression and miRNA/mRNA dysregulation have been associated with ovarian cancer. With the availability of whole-genome miRNA and mRNA sequencing we now have new potentials to study these associations. In this study, we performed a comprehensive analysis of miRNA and mRNA expression in ovarian cancer using an integrative network approach combined with association analysis.

We developed an integrative approach to construct a network that illustrates the complex interplay among miRNA and gene expression from a systems perspective. Our method is composed of expanding networks from eQTL associations, building network associations in eQTL analysis, and then combine the networks into an integrated network. This integrated network takes account of miRNA expression quantitative trait loci (eQTL) associations, miRNAs and their targets, protein-protein interactions, co-expressions among miRNAs and genes respectively. Applied to the ovarian cancer data set from The Cancer Genome Atlas (TCGA), we created an integrated network with 167 nodes containing 108 miRNA-target interactions and 145 from protein-protein interactions, starting from 44 initial eQTLs. This integrated network encompassed 26 genes and 14 miRNAs associated with cancer. In particular, 11 genes and 12 miRNAs in the integrated network are associated with ovarian cancer.

We demonstrated an integrated network approach that integrates multiple data sources at a systems level. We applied this approach to the TCGA ovarian cancer dataset, and constructed a network that provided a more inclusive view of miRNA and gene expression in ovarian cancer. This network included four separate types of interactions among miRNAs and genes. Simply analyzing each interaction component in isolation, such as the eQTL associations, the miRNA-target interactions or the protein-protein interactions, would create a much more limited network than the integrated one.