Identification of Hub Genes and Molecular Mechanisms of Association of PCOS, Breast, and Ovarian Cancers Using an Integrated Bioinformatics Analysis

Background: Oxidative stress plays a crucial role in various aspects of cancer and other diseases. While reactive oxygen species (ROS) serve as key signal molecules in physiological processes for the normal functioning of the female reproductive system, they have also been implicated in pathological processes such as polycystic ovary syndrome (PCOS). Some studies have reported a significantly higher risk of endometrial cancer in women with PCOS. However, the association of PCOS and common female cancers, such as breast and ovarian cancer, has not been thoroughly studied. Objective: The present study was undertaken to identify the hub genes and molecular pathways that are common amongst polycystic ovary syndrome, breast cancer, and ovarian cancers using bioinformatics based on the interactomes of these diseases. Methodology: Common differentially expressed genes (DEGs) of PCOS, breast, and ovarian cancer were retrieved from GEO to analyze datasets using R-software. An interactome of the common DEGs and their interacting partners was built in the STRING database, followed by analysis using different Cytoscape plugins to identify and validate the hub genes and their functional enrichment. Results: The identified hub proteins, namely CYBA, CYBB, DUOX1, NCF1, NCF2, NCF4, NOX1, NOX3, NOXA1, and NOXO1, are components or regulators of the NADPH oxidase, which catalyzes the production of ROS that could promote carcinogenesis and metastasis in patients suffering from PCOS. Conclusions: NOX-derived ROS are essential for normal cellular functions and host defense against pathogens. However, excessive ROS production can lead to oxidative stress, contributing to various diseases, including PCOS and cancers. Therefore, regulating NADPH oxidase activity could potentially serve as a therapeutic approach for PCOS management and prevent the initiation and progression of cancers in females suffering from PCOS.