Epigenetic effects of lifestyle in patients affected by gynecological tumors

Gynecological cancers are among the most frequent malignancies in women, with over 3.5 million women affected globally. This thesis focuses on endometrial (EC) and ovarian cancers (OC). EC is the sixth most common cancer in women, with obesity being a significant risk factor. Although less common, OC is the most lethal gynecological cancer due to the lack of specific symptoms and early detection biomarkers. Epigenetics investigates gene expression changes that occur without DNA sequence alterations but arise from environmental factors. microRNAs (miRNAs) are non-coding RNA molecules involved in the development of several diseases, including cancer. The aim of the present thesis was to clarify the epigenetic role of lifestyle in gynecological cancers. To achieve this goal, three tasks were planned: Task 1 addressed obesity-related EC, Task 2 explored physical activity’s role in OC, and Task 3 focused on OC organoid models. In Task 1, tissue and plasma samples from obese and non-obese EC patients, as well as from obese non-cancer women, were analysed to investigate the potential link between obesity and miRNA expression in EC. Results revealed a significant miRNA deregulation in obese EC patients, suggesting that obesity-induced epigenetic changes may contribute to EC development and progression. These findings could help identify new biomarkers for managing obese EC patients. Task 2 analysed miRNA expression in OC patients who were either enrolled in or not enrolled in a structured physical activity program. Results revealed significant variations in miRNA expression, suggesting that regular exercise may influence the molecular mechanisms underlying tumor biology. Lastly, Task 3 focused on developing a 3D OC organoid model to support future functional studies based on the previous findings. This study provides new insights into the epigenetic role of lifestyle in gynecological cancers, with potential implications for the development of personalized therapies based on miRNAs.