Abstract
To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place. Consequently, 53 genes were found, functionally enriched in pathways such as pyruvate metabolism, muscle system process and development of primary male sexual characteristics etc. We further lay our eyes on genes correlated with male sexual characteristics, which may be involved in the onset of both PCOS and breast cancer. Three genes were indicated to be associated with this process, including hydroxysteroid (17-beta) dehydrogenase 4/HSD17B4, platelet-derived growth factor receptor, alpha polypeptide/PDGFRA and high-mobility group box 2/HMGB2. Gene-drug interaction network about the three genes were then constructed. Drugs or chemicals that contribute to correcting the disorder of lipid metabolism were detected to restore the abnormal expression of the three genes in PCOS, such as simvastatin, bezafibrate, fenofibrate et al, which provide further choices for managing patients with PCOS.
Highlights
Polycystic ovary syndrome, which is short for PCOS, is a highly complex endocrine and metabolic disorder, characterized by clinical and/or biological signs of androgen excess with prolonged menstrual cycle, oligo ovulation or anovulation, hirsutism, polycystic ovarian, and high level of circulating androgens, and is frequently associated with insulin resistance and obesity
We further performed the Kaplan-Meier analysis in 3554 breast cancer patients in different stages using the differently expressed genes in both Gene Expression Omnibus (GEO) datasets
Those genes differently expressed in both datasets and have influence on breast cancer prognosis were hypothesized to be the key genes in pathogenesis of PCOS (Supplementary Table 1)
Summary
Polycystic ovary syndrome, which is short for PCOS, is a highly complex endocrine and metabolic disorder, characterized by clinical and/or biological signs of androgen excess with prolonged menstrual cycle, oligo ovulation or anovulation, hirsutism, polycystic ovarian, and high level of circulating androgens, and is frequently associated with insulin resistance and obesity. Large amount of data has proved that high serum level of androgens and estrogens were positively correlated with increased risk of breast cancer incidences and breast cancer recurrences [3,4,5,6,7,8,9,10,11,12,13]. Since androgen excess could contribute to the pathogenesis of both PCOS and breast cancer, there might be an overlap between dysregulated genes in PCOS and genes associated with breast cancer
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