Transcriptional deregulation in subcutaneous adipose tissue from severely obese patients is associated with cancer: focus on gender differences and role of type 2 diabetes. Transcriptional deregulation in subcutaneous adipose tissue from severely obese patients is associated with cancer: focus on gender differences and role of type 2 diabetes

Obesity is a major risk factor for a high number of secondary diseases, including cancer. Specific insights into the role of gender differences and secondary co-morbidities, such as type 2 diabetes (T2D) and cancer risk, are yet to be fully obtained. The aim of this study is thus to find a correlation between the transcriptional deregulation present in the subcutaneous adipose tissue of obese patients and the risk of cancer, in the presence of T2D, and considering gender differences. Through deep RNA-sequencing we highlighted the presence of both coding and non-coding deregulated RNAs, and we subsequently assessed their oncogenic risk. We correlated the oncogenes with anthropometrical parameters, highlighting significant trends. For each analysed condition we assessed the oncogenic pathways deregulated, the specific prognosis for different cancer types and the lncRNAs involvement in oncogenic networks and tissues. Our results provided a comprehensive characterization of oncogenesis correlation in subcutaneous adipose tissue, providing specific insights into the oncogenic prognosis for obese, diabetic or gender-specific differences. These results could shed light on new molecular targets to be specifically modulated in obesity and highlight which cancers should be most looked out for a better prevention in obesity affected patients. Overall design: Biopsies of SAT collected from a total of 20 subjects: 5 healthy normal weight women (CTRL, age 37 ± 6.7 years, BMI 24.3 ± 0.9 kg/m2), 5 obese women (OBF, age 41 ± 12.5 years, BMI 38.2 ± 4.6 kg/m2), 5 obese women with T2D (OBT2D; age 54.6 ± 14.9 years, BMI 38.1 ± 11.8 kg/m2) and 5 obese men (OBM, age 42.4 ± 6.58 years, BMI 36.9 ± 3.5 kg/m2)

肥胖是包括癌症在内的诸多继发性疾病的核心危险因素。目前学界对于性别差异以及2型糖尿病（type 2 diabetes, T2D）这类继发性共病与癌症风险之间的具体关联机制，尚未完全厘清。本研究旨在探究肥胖患者皮下脂肪组织（subcutaneous adipose tissue, SAT）中存在的转录失调现象，结合2型糖尿病共存状态与性别差异，分析其与癌症风险的相关性。
通过深度RNA测序，本研究鉴定出了编码RNA与非编码RNA两类失调转录本，并进一步评估了它们的致癌风险。将致癌基因与人体测量学参数进行关联分析后，我们揭示了多项具有统计学意义的变化趋势。针对每一种分析条件，本研究还评估了失调的致癌通路、不同癌症类型的特异性预后，以及长链非编码RNA（long non-coding RNA, lncRNA）在致癌调控网络与组织中的参与作用。
本研究结果全面表征了皮下脂肪组织中致癌相关的关联特征，为肥胖、糖尿病群体以及性别差异相关的致癌预后提供了针对性的科学见解。上述研究成果可为肥胖患者的靶向干预提供全新的分子靶点，并明确需重点筛查的癌症类型，以优化肥胖人群的癌症预防策略。
整体实验设计：本研究共纳入20名受试者的皮下脂肪组织活检样本，具体分组如下：5名健康正常体重女性（对照组，CTRL，年龄37±6.7岁，体质量指数BMI 24.3±0.9 kg/m²）、5名单纯肥胖女性（OBF，年龄41±12.5岁，BMI 38.2±4.6 kg/m²）、5名合并2型糖尿病的肥胖女性（OBT2D；年龄54.6±14.9岁，BMI 38.1±11.8 kg/m²）以及5名单纯肥胖男性（OBM，年龄42.4±6.58岁，BMI 36.9±3.5 kg/m²）