Transcriptome Analysis of Subcutaneous Adipose Tissue from Severely Obese Patients Highlights Deregulation Profiles in Coding and Non-Coding Oncogenes

Obesity is a major risk factor for a large number of secondary diseases, including cancer.Specific insights into the role of gender differences and secondary comorbidities, such as type2 diabetes (T2D) and cancer risk, are yet to be fully identified. The aim of this study is thus tofind a correlation between the transcriptional deregulation present in the subcutaneous adiposetissue of obese patients and the oncogenic signature present in multiple cancers, in the presence ofT2D, and considering gender differences. The subcutaneous adipose tissue (SAT) of five healthy,normal-weight women, five obese women, five obese women with T2D and five obese men weresubjected to RNA-sequencing, leading to the identification of deregulated coding and non-codingRNAs, classified for their oncogenic score. A panel of DE RNAs was validated via Real-TimePCR and oncogene expression levels correlated the oncogenes with anthropometrical parameters,highlighting significant trends. For each analyzed condition, we identified the deregulated pathwaysassociated with cancer, the prediction of possible prognosis for different cancer types and the lncRNAsinvolved in oncogenic networks and tissues. Our results provided a comprehensive characterizationof oncogenesis correlation in SAT, providing specific insights into the possible molecular targetsimplicated in this process. Indeed, the identification of deregulated oncogenes also in SAT highlightshypothetical targets implicated in the increased oncogenic risk in highly obese subjects. These resultscould shed light on new molecular targets to be specifically modulated in obesity and highlight whichcancers should receive the most attention in terms of better prevention in obesity-affected patients.