Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide analysis of uterine natural killer cell gene expression from lean and obese women in early pregnancy

ABSTRACT: Analysis of gene expression in uterine natural killer (NK) cells purified from either lean (control) or obese pregnanct women. The studys' aim is to identify differentially expressed genes and pathways in natural killer cells that are affected by maternal obesity. Results provide mechanitic insight into gene pathways altered in the condition of obeisty. Total RNA obtained from immuno-magnetic bead purified natural killer cells from uterine decidual mucosa from 7 to 10 week old pregnancies from 13 lean (BMI 20-24.9) and 11 obese (BMI >30) women. All women were between 19 and 35 years of age. In addition to BMI, blood serum CRP (hsCRP), a measure of inflammation, was measured via ELISA.

ORGANISM(S): Homo sapiens

SUBMITTER: Alexander Beristain

PROVIDER: E-GEOD-75091 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description: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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Genome-wide analysis of uterine natural killer cell gene expression from lean and obese women in early pregnancy

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