BIOMARKER STUDIES REVEALING MOLECULAR LINKS BETWEEN POLYCYSTIC OVARY SYNDROME AND BREAST CANCER

Abstract

Breast cancer becomes the most frequent and widespread cancer impacting women globally. Frequently, it is monitored that females diagnosed with the condition PCOS display a greater inclination towards the expansion of breast cancer. Many studies demonstrate an increased risk of breast cancer in females diagnosed with PCOS, and the interrelation shared by both disorders remains unsolved to date. Available studies data depict an essential role of chronic unopposed estrogen exposure, hyperandrogenism, and hyperinsulinemia in modulating the growth of cells and their proliferation, and also serve a potent role acting as a tumor suppressor in numerous cancers, which also involve breast cancer. For a better transparency of this interconnection, we used an advanced bioinformatics approach in which the collection of disease-related genes takes place with the help of the Comparative Toxicogenomics Database (CTD). Quantitative and qualitative comparison analysis takes place between both disorders, breast cancer and PCOS, and identification of 17 shared common genes takes place. Furthermore, the construction of the three regulatory networks model takes place with the help of the online platform NetworkAnalyst. Networks named as gene–miRNA interaction networks, gene–transcription factor networks, and tissue-specific co-expression networks The regulatory analysis of all three networks led to the identification of NAMPT (Nicotinamide Phosphoribosyltransferase) as the critical key hub gene, which correlates with all three regulatory networks of disorders, breast cancer, and PCOS. NAMPT plays a vital role in the formation of the NAD+ biosynthetic pathway, cellular metabolism, repair of DNA, and balance energy, and the extracellular form of NAMPT serves as an inflammatory interconnector adipokine and triggers resistance to insulin, formation of new blood vessels, and survival of cancerous cells. NAMPT plays a double role as it bridges the link between metabolic dysregulation of PCOS and the growth and survival of breast cancer cells. The current research broadcasts an overlapping link between PCOS and breast cancer, shared molecular and genetic pathways, and how they may be disrupted due to PCOS. In addition, we postulate a novel mechanism and predict the outcomes of drugs for cancer linked with PCOS, which potentially contribute to the emergence of a novel therapeutic strategy.