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| Status |
Public on Mar 08, 2016 |
| Title |
Effect of obesity on molecular characteristics of invasive breast tumors: gene expression analysis of 405 tumors by BMI |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Background: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.
Methods: Affymetrix U133 2.0 gene expression data were generated for 405 primary breast tumors using RNA isolated from laser microdissected tissues. Patients were classified as normal-weight (BMI<25), overweight (BMI 25-29.9) or obese (BMI>30). Statistical analysis was performed by ANOVA using Partek Genomics Suite version 6.6 using a false discovery rate <0.05 to define significance.
Results: Obese patients were significantly more likely to be diagnosed >50 years or with African American ancestry compared to lean or overweight women. Pathological characteristics, including tumor stage, size or grade, lymph node status, intrinsic subtype, and breast cancer mortality did not differ significantly between groups. No significant gene expression differences were detected by BMI In a non-stratified analysis which included all subtypes or within luminal B, HER2-enriched or basal-like subtypes. Within luminal A tumors, however, 84 probes representing 77 genes from pathways such as cell cycle, p53 and mTOR signaling, tight junctions and a number of cancer associated pathways were differentially expressed.
Conclusions: Identification of transcriptome differences in luminal A tumors from normal-weight compared to obese women suggests that obesity alters gene expression within ER+ tumor epithelial cells. Alterations of pathways involved in cell cycle control, tumorigenesis and metabolism may promote cellular proliferation and provide a molecular explanation for less favorable outcome of obese women with breast cancer. Targeted treatments, such as mTOR inhibitors, may allow for improved treatment and survival of obese women, especially African American women, who are more likely to be obese and suffer outcome disparities.
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| Overall design |
Two to five serial sections (8 um thick) were cut, mounted on glass PEN foil slides (Leica Microsystems, Wetzlar, Germany), stained using the LCM staining kit (Applied Biosystems, Foster City, CA) and laser microdissected on an ASLMD laser microdissection system (Leica Microsystems, Wetzlar, Germany). Slide preparation, staining and cutting were performed within a 15 minute period to preserve RNA integrity. RNA was then isolated using the RNAqueous-Micro kit (Applied Biosystems, Foster City, CA) and treated with DNase I to remove any contaminating genomic DNA. RNA integrity was assessed using the 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA), converted to biotin-labeled aRNA using two rounds of amplification with the MessageAmpII aRNA Amplification kit (Applied Biosystems, Foster City, CA), and the concentration and quality of the samples was measured with the NanoDrop 1000 (NanoDrop Products, Wilmington, DE) and 2100 Bioanalyzer. Hybridization, washing, staining and scanning of HG U133A 2.0 arrays (Affymetrix, Santa Clara, CA) were conducted according to manufacturer’s protocols. The gene expression data were analyzed with Partek® Genomics Suite v 6.6 (Partek Incorporated). Probe set intensities were obtained by robust multi-array average background correction, quantile normalization, median polish summarization, and log2 transformation. Data integrity was then assessed by standard GeneChip® quality control parameters.
Please note that some of the patients (19 out of 424) did not have a BMI available from the diagnosis date and so they were coded Unknown for BMI and not used in downstream analysis.
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| Contributor(s) |
Ellsworth R |
| Citation(s) |
27148454 |
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| Submission date |
Mar 07, 2016 |
| Last update date |
Dec 06, 2018 |
| Contact name |
Rachel Ellsworth |
| E-mail(s) |
[email protected]
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| Organization name |
Windber Research Institute
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| Department |
Clinical Breast Care Project
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| Street address |
620 Seventh Street
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| City |
Windber |
| State/province |
PA |
| ZIP/Postal code |
15963 |
| Country |
USA |
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| Platforms (1) |
| GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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| Samples (424)
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| Relations |
| BioProject |
PRJNA314509 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE78958_RAW.tar |
833.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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