A gene transcription signature of obesity in breast cancer

作者：Creighton Chad J; Sada Yvonne H; Zhang Yiqun; Tsimelzon Anna; Wong Helen; Dave Bhuvanesh; Landis Melissa D; Bear Harry D; Rodriguez Angel; Chang Jenny C^*

来源：Breast Cancer Research and Treatment, 2012, 132(3): 993-1000.

DOI：10.1007/s10549-011-1595-y

• Obesity
• Breast cancer
• BMI
• Insulin-like growth factor
• IGF
• Gene expression profiling

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 103 tumors for which the patients%26apos; body mass index (BMI) was ascertained. Sample profiles were stratified according to patients%26apos; obesity phenotype defined as normal (BMI %26lt; 25), overweight (BMI 25-29.9), or obese (BMI a parts per thousand yen 30). Widespread gene expression alterations were evident in breast tumors from obese patients as compared to other tumors, allowing us to define an obesity-associated cancer transcriptional signature of 662 genes. In multiple public expression data sets of breast cancers (representing %26gt; 1,500 patients), manifestation of the obesity signature patterns correlated with manifestation of a gene signature for IGF signaling and (to a lesser extent) with lower levels of estrogen receptor. In one patient cohort, manifestation of the obesity signature correlated with shorter time to metastases. A number of small molecules either induced or suppressed the obesity-associated transcriptional program in vitro; estrogens alpha-estradiol, levonorgestrel, and hexestrol induced the program, while several anti-parkinsonian agents targeting neurotransmitter receptor pathways repressed the program. Obesity in breast cancer patients appears to impact the gene expression patterns of the tumor (perhaps as a result of altered body chemistry). These results warrant further investigation of obesity-associated modifiers of breast cancer risk and disease outcome.

• 出版日期2012-4