Gene transcription signature of obesity in breast cancer

Obesity is thought to contribute to worse disease outcome in breast cancer as a result of increased levels of adipocyte-secreted endocrine factors, insulin, and insulin-like growth factors (IGFs) that accelerate tumor cell proliferation and impair treatment response. We examined the effects of patient obesity on primary breast tumor gene expression, by profiling transcription of a set of tumors for which the patients’ body mass index (BMI) was ascertained. Sample profiles were stratified according to patients’ obesity phenotype defined as normal (BMI <25), overweight (BMI 25-29.9), or obese (BMI>30). Widespread alterations in gene expression were evident in breast tumors from obese patients as compared to tumors from other patients, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. Keywords: two group comparison Primary breast tumor specimens were obtained from patients. Study volunteers completed questionnaires used to define historically normal (BMI<=24.9), overweight (BMI 25-29.9), or obese (BMI>=30) patient categories according to established WHO criteria.

现有研究认为，肥胖可通过提升脂肪细胞分泌的内分泌因子、胰岛素以及胰岛素样生长因子（insulin-like growth factors, IGFs）的水平，加速肿瘤细胞增殖并削弱治疗应答反应，进而导致乳腺癌患者的疾病转归更差。本研究通过对一批已知患者体质量指数（body mass index, BMI）的乳腺肿瘤样本进行转录组分析，探究了患者肥胖状态对原发性乳腺肿瘤基因表达的影响。我们依据患者的肥胖表型对样本转录谱进行分层，肥胖表型分为体重正常组（BMI＜25）、超重组（BMI 25~29.9）以及肥胖组（BMI＞30）。与其他患者的肿瘤样本相比，肥胖患者的乳腺肿瘤中存在广泛的基因表达异常，据此我们鉴定出了包含662个基因的肥胖相关乳腺癌转录特征。关键词：两组比较 本研究从患者体内获取原发性乳腺肿瘤标本，研究对象填写问卷，依据既定的世界卫生组织（WHO）标准，将患者划分为既往体重正常组（BMI≤24.9）、超重组（BMI 25~29.9）以及肥胖组（BMI≥30）三类。