Project description:Control samples used to performed gene expression comparison with breast cancer tissues. mRNA samples from normal breast tissue were amplified, labeled, and hybridized to the Affymetrix GeneChip Human Exon 1.0 ST array. After normalization and analysis of the microarray data using Partek® software (http://www.partek.com).
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.
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.
Project description:The Susan G. Komen Tissue Bank at Indiana University Simon Comprehensive Cancer Center (KTB) is the only repository of normal breast tissues donated by healthy women. Here, we examined the transcriptome profiling of normal breasts from 190 healthy women, including 62 African Americans, 11 Asians, and 109 Caucasians. Correlation analysis between geen expression and risk factors for breast cancer (such as smoking, BMI, age, racial background) was performed.
Project description:Obesity has been linked to lifestyle and recently have been associated to DNA methylation changes that may cause alterations in the adipogenesis and lipid storage processes and contribute to the pathological state. We enrolled Obese (Ob) and Normal Weight (NW) women. We observed that DNA methylation patterns are different between normal weight and obese women. This can alter gene expression patterns affecting adipogenesis and lipid storage. This results confirms that an obesogenic lifestyle can promote epigenetic changes in the human DNA.
Project description:The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 480,000 CpGs in a total of 407 samples, including 50 normal samples from healthy women, 42 matched normal-adjacent breast cancer pairs (84 samples), 263 unmatched breast cancers, 7 normal samples from BRCA1 carriers and 4 BRCA1 breast cancers. ***WARNING: incomplete metadata supplied for this study***
Project description:Breast cancer develops through the accumulation of genomic changes in the ductal epithelia cells of normal breast tissue. A determination of whether gene expression changes in ductal cells is associated with an increased risk for breast cancer is needed. We sought to determine if the global gene expression profiles of ductal cells of women at high risk for breast cancer or with cytologic ductal epithelial atypia differed from those of women at normal risk or without cytologic atypia. We used microarrays to detail the gene expression profile of breast ductal cells associated with normal risk or high risk for sporadic breast cancer and with or without cytologic epithelial atypia. We did not identify any separation of the sample groups (normal risk vs high-risk, or atypia vs nonatypia) according to expression of subgroups of genes.
Project description:On the basis of prognostic information provided by the PAM50 predictor, we evaluated how samples grouped relative to the other breast tumor subtypes. mRNA samples from 24 patients were amplified, labeled, and hybridized to the Affymetrix GeneChip Human Exon 1.0 ST array. After normalization and analysis of the microarray data using PartekM-BM-. software (http://www.partek.com), we clustered all samples using the PAM50 predictor. We analyzed tumors from 24 patients with breast cancer using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by AffymetrixExpression Console and analysed using Partek software
Project description:On the basis of prognostic information provided by the PAM50 predictor, we evaluated how samples grouped relative to the other breast tumor subtypes. mRNA samples from 24 patients were amplified, labeled, and hybridized to the Affymetrix GeneChip Human Exon 1.0 ST array. After normalization and analysis of the microarray data using Partek® software (http://www.partek.com), we clustered all samples using the PAM50 predictor.