Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Cancer. 2022 Sep 15;128(18):3297-3309. doi: 10.1002/cncr.34356. Epub 2022 Jul 6.
A complex relationship between adipose tissue and malignancy, involving an inflammatory response, has been reported. The goal of this work was to assess the prevalence of white adipose tissue (WAT) inflammation in patients with endometrial cancer (EC), and the association with circulating inflammation markers. Furthermore, the aim was to characterize the pathways activated in and the cell type composition of adipose tissue in patients with EC.
Adipose tissue and blood samples were prospectively collected from 101 patients with EC at initial surgery. WAT inflammation was determined based on adipocytes surrounded by macrophages forming crown-like structures. Circulating levels of metabolic syndrome-associated and inflammatory markers were quantified. RNA-sequencing was performed on adipose samples (n = 55); differential gene expression, pathway, and cellular decomposition analyses were performed using state-of-the-art bioinformatics methods.
WAT inflammation was identified in 46 (45.5%) of 101 EC patients. Dyslipidemia, hypertension, and diabetes mellitus were significantly associated with WAT inflammation (p < .05). WAT inflammation was associated with greater body mass index (p < .001) and higher circulating levels of leptin, high-sensitivity C-reactive protein, and interleukin-6, as well as lower levels of adiponectin and sex hormone-binding globulin (p < .05). Transcriptomic analysis demonstrated increased levels of proinflammatory and pro-neoplastic-related gene expression in inflamed omental adipose tissue.
WAT inflammation is associated with metabolic syndrome, obesity, and inflammatory markers, as well as increased expression of proinflammatory and proneoplastic genes.
已有报道称，脂肪组织与恶性肿瘤之间存在复杂的关系，涉及炎症反应。本研究旨在评估子宫内膜癌（EC）患者白色脂肪组织（WAT）炎症的发生率，并探讨其与循环炎症标志物的相关性。此外，本研究还旨在对 EC 患者脂肪组织中激活的途径和细胞类型组成进行特征描述。
前瞻性收集了 101 例初次手术的 EC 患者的脂肪组织和血液样本。根据被巨噬细胞环绕形成冠状结构的脂肪细胞来确定 WAT 炎症。定量检测与代谢综合征相关的循环炎症标志物水平。对 55 例脂肪样本进行 RNA 测序；使用最先进的生物信息学方法进行差异基因表达、途径和细胞分解分析。
在 101 例 EC 患者中，有 46 例（45.5%）存在 WAT 炎症。血脂异常、高血压和糖尿病与 WAT 炎症显著相关（p<0.05）。WAT 炎症与更高的体重指数（p<0.001）和更高的循环瘦素、高敏 C 反应蛋白和白细胞介素-6 水平，以及更低的脂联素和性激素结合球蛋白水平相关（p<0.05）。转录组分析表明，炎症性大网膜脂肪组织中促炎和促瘤相关基因的表达水平升高。
WAT 炎症与代谢综合征、肥胖和炎症标志物有关，以及促炎和促瘤基因的表达增加。
