Microarray study of tumoral tissue transcriptome of breast cancer in mexican women who are overweight or obese
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PROVIDER: PRJNA435533 | ENA |
REPOSITORIES: ENA
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Project description:In this work, transcriptoma of invasive breast carcinoma was studied by means of microarray expression in Mexican women who are overweight or obese. The dysfunction of the adipokines signaling pathways has recently been linked to more aggressive features of breast cáncer. We hypothesized that there are changes related to the signaling of adipokines in the expression profile of invasive breast carcinoma of Mexican women with overweight or obesity. The objectives were as follows: 1) Determine the expression profile of tumour tissue of Mexican women who are overweight or obese by comparing tumoral tissue and non -tumoral tissue, both from the same patient, 2) Identification of over- or underexpressed genes involved in signalling pathways related to adipokines and the tumour process, 3) Identify the signalling pathways that presented genes with expression changes and were related to adipokines and the tumoural process.
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Project description:Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity. Gene expression profiles of normal breast tissue from reduction mammoplasty patients were evaluated by whole genome microarrays to identify patterns associated with obesity status (normal-weight, body mass index (BMI) <25; overweight, BMI 25-29.9; obese, BMI > or equal to 30). The presence of macrophage-enriched inflammatory loci with immunopositivity for CD68 protein was evaluated by immunohistochemistry (IHC). After adjusting for confounding by age, 760 genes were differentially expressed (203 up and 557 down; FDR = 0.026) between normal-weight and obese women. Gene ontology analysis suggested significant enrichment for pathways involving IL-6, IL-8, CCR5 signaling in macrophages and RXRalpha and PPARalpha activation, consistent with a pro-inflammatory state and suggestive of macrophage infiltration. Gene set enrichment analysis also demonstrated that the genomic signatures of monocytes and macrophages were over-represented in the obese group with FDR of 0.08 and 0.13, respectively. Increased macrophage infiltration was confirmed by IHC, which showed that the breast adipose tissue of obese women had higher average macrophage counts (mean = 8.96 vs. 3.56 in normal-weight women) and inflammatory foci counts (mean = 4.91 vs. 2.67 in normal-weight women). Obesity is associated with local inflammation and macrophage infiltration in normal human breast adipose tissues. Given the role of macrophages in carcinogenesis, these findings have important implications for breast cancer etiology and progression. 72 normal breast tissue samples from patients undergoing reduction mammoplasty. Reference design.
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Project description:Activation of inflammatory pathways is one plausible mechanism underlying the association between obesity and increased breast cancer risk. However, macrophage infiltration and local biomarkers of inflammation in breast adipose tissue have seldom been studied in association with obesity. Gene expression profiles of normal breast tissue from reduction mammoplasty patients were evaluated by whole genome microarrays to identify patterns associated with obesity status (normal-weight, body mass index (BMI) <25; overweight, BMI 25-29.9; obese, BMI > or equal to 30). The presence of macrophage-enriched inflammatory loci with immunopositivity for CD68 protein was evaluated by immunohistochemistry (IHC). After adjusting for confounding by age, 760 genes were differentially expressed (203 up and 557 down; FDR = 0.026) between normal-weight and obese women. Gene ontology analysis suggested significant enrichment for pathways involving IL-6, IL-8, CCR5 signaling in macrophages and RXRalpha and PPARalpha activation, consistent with a pro-inflammatory state and suggestive of macrophage infiltration. Gene set enrichment analysis also demonstrated that the genomic signatures of monocytes and macrophages were over-represented in the obese group with FDR of 0.08 and 0.13, respectively. Increased macrophage infiltration was confirmed by IHC, which showed that the breast adipose tissue of obese women had higher average macrophage counts (mean = 8.96 vs. 3.56 in normal-weight women) and inflammatory foci counts (mean = 4.91 vs. 2.67 in normal-weight women). Obesity is associated with local inflammation and macrophage infiltration in normal human breast adipose tissues. Given the role of macrophages in carcinogenesis, these findings have important implications for breast cancer etiology and progression.
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Project description:The prevalence of obesity has been increasing rapidly worldwide during the past two decades. This is alarming, since obesity has considerable effects on morbidity and mortality. The majority of gene expression studies about the effect of obesity and weight loss have been performed using the adipose tissue for mRNA extraction. However, also the liver plays a central role in maintaining energy balance. To our knowledge, no overall analysis of hepatic gene expression in response to changes in nutritional status has been made in humans Therefore, it is important to investigate how a short-time hypocaloric diet affects overall hepatic gene expression and the metabolic profile in a group of overweight and obese women. The subjects (n=31) were middle-aged, overweight (BMI>25 kg/m2) women with gallstone disease scheduled for an elective gallbladder operation. The intervention subjects were placed on a hypocaloric AHA step I diet with a recommended daily energy intake of 5.0 MJ. The objective was to reduce 0.5 kg of body weight per week. The control subjects were instructed to continue their habitual diet and not to lose weight. Basic clinical measurements and laboratory analyses were performed twice at baseline and at two week intervals during the weight reduction period. Surgical liver biopsies were obtained at the end of the weight reduction period. RNA samples of 4 individuals from the intervention group and 4 individuals from the control group were selected for the microarray analysis. The results from the microarray analysis were fairly surprising. Only one gene was up-regulated and the rest 142 down-regulated in the diet intervention group compared to the control group when a minimum of 2-fold change was set as the limit. The global decrease in hepatic gene expression was unexpected but the results are interesting, with several genes not previously linked to weight reduction. The decrease in triglyceride and fasting plasma insulin concentrations observed in our study is in accordance with results from many previous weight-loss trials. Keywords: Overall hepatic gene expression associated with obesity and moderate weight loss in a group of overweight and obese middle-aged women.
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