Department of Biomedical and Clinical Sciences "L. Sacco", School of Medicine, University of Milano, Via Grassi 74, 20157 Milano, Italy.
Pediatric Clinical Research Centre Fondazione "Romeo ed Enrica Invernizzi", University of Milano, Via G.B. Grassi 74, 20157 Milano, Italy.
Int J Mol Sci. 2021 Feb 17;22(4):1989. doi: 10.3390/ijms22041989.
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 type 2 diabetes (T2D) and cancer risk, are yet to be fully identified. 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 oncogenic signature present in multiple cancers, in the presence of T2D, 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 were subjected to RNA-sequencing, leading to the identification of deregulated coding and non-coding RNAs, classified for their oncogenic score. A panel of DE RNAs was validated via Real-Time PCR and oncogene expression levels correlated the oncogenes with anthropometrical parameters, highlighting significant trends. For each analyzed condition, we identified the deregulated pathways associated with cancer, the prediction of possible prognosis for different cancer types and the lncRNAs involved in oncogenic networks and tissues. Our results provided a comprehensive characterization of oncogenesis correlation in SAT, providing specific insights into the possible molecular targets implicated in this process. Indeed, the identification of deregulated oncogenes also in SAT highlights hypothetical targets implicated in the increased oncogenic risk in highly obese subjects. These results could shed light on new molecular targets to be specifically modulated in obesity and highlight which cancers should receive the most attention in terms of better prevention in obesity-affected patients.
肥胖是许多继发性疾病的主要危险因素，包括癌症。然而，性别差异和继发性合并症（如 2 型糖尿病（T2D）和癌症风险）的具体作用仍有待充分确定。因此，本研究旨在寻找肥胖患者皮下脂肪组织中存在的转录失调与存在 T2D 时多种癌症中存在的致癌特征之间的相关性，并考虑到性别差异。对五名健康、体重正常的女性、五名肥胖女性、五名肥胖合并 T2D 的女性和五名肥胖男性的皮下脂肪组织（SAT）进行了 RNA 测序，鉴定出编码和非编码 RNA 的失调，并根据其致癌评分进行了分类。通过实时 PCR 验证了一组差异表达的 RNA，并将癌基因表达水平与人体测量参数相关联，突出了显著趋势。对于每种分析的情况，我们确定了与癌症相关的失调途径，预测了不同癌症类型的可能预后，并确定了参与致癌网络和组织的 lncRNAs。我们的结果全面描述了 SAT 中致癌作用的相关性，为该过程中可能涉及的分子靶标提供了具体见解。事实上，在 SAT 中也鉴定出失调的癌基因，突出了在高度肥胖的患者中，这一过程中涉及的假设性分子靶标。这些结果可以为肥胖症中特异性调节的新分子靶标提供启示，并强调在肥胖症患者中应更加关注哪些癌症，以更好地预防癌症。
