Plasma metabolic fingerprint for breast cancer (MS) - part I
Ontology highlight
ABSTRACT:
ORGANISM(S): Human Homo Sapiens
TISSUE(S): Blood
DISEASE(S): Cancer
SUBMITTER: 
Monica Cala
PROVIDER: ST000918 | MetabolomicsWorkbench | Fri Dec 29 00:00:00 GMT 2017
REPOSITORIES: MetabolomicsWorkbench
Similar Datasets
Project description:Background: Differences in breast cancer outcomes according to race/ethnicity have been reported. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable fractions of European, Indigenous American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Hispanic/Latinas compared to non-Hispanic Whites (NHW) even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but equivalent knowledge is lacking in Hispanic/Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian H/L women was Luminal B as defined by surrogate St. Gallen 2013 criteria. In this study we explored ancestry-associated differences in molecular profiles of Luminal B tumors among these highly admixed women. Methods: We performed whole-transcriptome RNA-seq analysis in 42 Luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to Luminal subtype and to the proportion of European and Indigenous American ancestry and performed differential expression analysis comparing Luminal B against Luminal A tumors according to the assigned ancestry groups. Results: We found 5 genes potentially modulated by genetic ancestry: ERBB2 (Fold Change = 2.367, padj < 0.01), GRB7 (Fold Change = 2.327, padj < 0.01), GSDMB (Fold Change = 1.723, padj < 0.01, MIEN1 (Fold Change = 2.195, padj < 0.01 and ONECUT2 (Fold Change = 2.204, padj < 0.01). In the replication set we found a statistical significant association between European ancestry fraction and the expression levels of ERBB2 (p = 0.02, B = 2.49) and ONECUT2 (p = 0.04, B = -4.87). We also observed statistical significant associations for ERBB2 expression with Indigenous American ancestry (p < 0.001, B = 3.82). This association was not biased by the distribution of HER2+ tumors among the groups analyzed. Conclusions: Our results suggest that genetic ancestry in Hispanic/Latina women might modify ERBB2 gene expression in Luminal tumors. Further analyses are needed to confirm these findings and explore their prognostic value.
2017-10-04 | GSE101927 | GEO
Project description:The origin and the contribution of breast tumor heterogeneity to its progression are not clear. We investigated the effect of a growing orthotopic tumor formed by an aggressive estrogen receptor (ER)-negative breast cancer cell line on the metastatic potential of a less aggressive ER-positive breast cancer cell line for the elucidation of how the presence of heterogeneous cancer cells might affect each other’s metastatic behavior.
2011-05-25 | GSE27515 | GEO
Project description:Being molecularly heterogeneous, breast cancer tends to be a complicated oncological disease with high incidence rates throughout the world. The primary aim of this study was to identify the set of serum proteins with discriminatory capabilities towards the four major subtypes of breast cancer. We employed multipronged quantitative proteomic approaches like 2D-DIGE, iTRAQ and SWATH-MS and identified 307 differentially regulated proteins. Luminal A subtype consisted of 24, Luminal B subtype 38, HER2 Enriched subtype 17 and Triple negative breast cancer subtype 10 differentially regulated subtype specific proteins. These specific proteins were further subjected to bioinformatic analysis viz. PANTHER, DAVID and LENS which revealed the involvement in platelet degranulation, fibrinolysis, lipid metabolism, immune response, complement activation, blood coagulation, immune cell activation, glycolysis, amino acid biosynthesis and cancer signaling pathways in the subtypes of the breast cancer. The significant discrimination efficiency of the models generated through multivariate statistical analysis was decent to distinguish each of the four subtypes from controls. Further, some of the statistically significant differentially regulated proteins were verified and validated by immunoblotting and mass spectrometry based selected reaction monitoring (SRM) approach. Our Multipronged proteomics approaches revealed panel of serum proteins specifically altered for individual subtypes of breast cancer.
2017-05-15 | PXD006441 | Pride
Project description:Compositional statistics and random gene-sets were used to assign the tumor site of origin and histopathology of 18 epithelial ovarian cancer cell lines
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Project description:Tissue of the breast is heterogeneous, consisting of a variety of cell types and connective tissue. This heterogeneity is also present in breast tumors and will complicate proteomic analysis, as it is not always clear whether a signal originates from the stromal environment, from normal epithelial or tumor cells. Here we microdissected a variety of cell types and stroma from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Although this heterogeneity complicated detection of differentially abundant proteins, several markers were exclusively detected in stroma. However, as heterogeneity in the stroma is more difficult to be reduced through microdissection, comparative analysis was most informative in microdissected cells of epithelial origin, and provided a relatively complete picture of malignant transformations.
2017-01-11 | PXD003632 | Pride
Project description:Breast cancer is a heterogeneous disease described in well-recognized biological subtypes. Particularly, gene expression profiling has revealed 5 intrinsic subtypes of breast cancer characterized by different biological and clinical features. The diversity of the intrinsic subtypes across human population has been limited described, and there is few information about the genomic architecture of breast tumors in Mexican or Hispanic populations. In this study, we performed PAM50 assay, based in Affymetrix microarray profiling of 128 fresh frozen tumors from Mexican Latino Hispanic population, to describe the overall distribution of subtypes, and characterize the relation to clinicopathologic characteristics. As well, we correlated the mRNA expression patterns with specific copy number alterations (CPA), in order to analyze their role in breast tumors. A total of 100 blood-tumor samples were assayed using Affymetrix 6.0 SNP arrays; segmentation analysis and GISTIC were performed to identify focal amplifications or deletions. The distribution of PAM50 intrinsic subtypes in our cohort was computed to be 44% luminal A, 20% luminal B, 12.0% HER2-enriched, 12% basal-like, and 12% normal-like. Study comparison with the literature mainly TCGA and METABRIC (most of the patients came from Caucasian population), as well as LACE (which describe a population study) show a similar distribution of the intrinsic subtypes within Hispanic and Caucasian populations. Interestingly, basal-like subtype is less represented than in African-American race. The sum of sensitivity and specificity between the clinicopathologic and intrinsic subtype categories across 4 groups (excluding normal-like) was 50% and 87.5%, respectively. Differentially expression profiles within the subtypes reveal a set of genes altered in each group with biological relevance to stablish the phenotypical characteristics of each subtype. Our analyses confirmed the already reported copy number data. Importantly, many of the copy number profiles correlated with mRNA subtype. With this analysis we can conclude that breast cancer intrinsic subtypes have been reproduced in Mexican population contributing to the description of the PAM50 subtypes among multiple ethnic groups based on a gene expression assay. Our observation based in the integrative genomic analysis of mRNA expression and CPA allowed us to define gene circuits and phenotypic characteristics that can explain the heterogeneity of breast cancer subtypes.
2018-08-31 | GSE87048 | GEO
Project description:Breast cancer is a heterogeneous disease described in well-recognized biological subtypes. Particularly, gene expression profiling has revealed 5 intrinsic subtypes of breast cancer characterized by different biological and clinical features. The diversity of the intrinsic subtypes across human population has been limited described, and there is few information about the genomic architecture of breast tumors in Mexican or Hispanic populations. In this study, we performed PAM50 assay, based in Affymetrix microarray profiling of 128 fresh frozen tumors from Mexican Latino Hispanic population, to describe the overall distribution of subtypes, and characterize the relation to clinicopathologic characteristics. As well, we correlated the mRNA expression patterns with specific copy number alterations (CPA), in order to analyze their role in breast tumors. A total of 100 blood-tumor samples were assayed using Affymetrix 6.0 SNP arrays; segmentation analysis and GISTIC were performed to identify focal amplifications or deletions. The distribution of PAM50 intrinsic subtypes in our cohort was computed to be 44% luminal A, 20% luminal B, 12.0% HER2-enriched, 12% basal-like, and 12% normal-like. Study comparison with the literature mainly TCGA and METABRIC (most of the patients came from Caucasian population), as well as LACE (which describe a population study) show a similar distribution of the intrinsic subtypes within Hispanic and Caucasian populations. Interestingly, basal-like subtype is less represented than in African-American race. The sum of sensitivity and specificity between the clinicopathologic and intrinsic subtype categories across 4 groups (excluding normal-like) was 50% and 87.5%, respectively. Differentially expression profiles within the subtypes reveal a set of genes altered in each group with biological relevance to stablish the phenotypical characteristics of each subtype. Our analyses confirmed the already reported copy number data. Importantly, many of the copy number profiles correlated with mRNA subtype. With this analysis we can conclude that breast cancer intrinsic subtypes have been reproduced in Mexican population contributing to the description of the PAM50 subtypes among multiple ethnic groups based on a gene expression assay. Our observation based in the integrative genomic analysis of mRNA expression and CPA allowed us to define gene circuits and phenotypic characteristics that can explain the heterogeneity of breast cancer subtypes.
2018-08-31 | GSE86374 | GEO
Project description:Purpose: We generated extensive transcriptional and proteomic profiles from a Her2-driven mouse model of breast cancer that closely recapitulates human breast cancer. This report makes these data publicly available in raw and processed forms, as a resource to the community. Importantly, we previously made biospecimens from this same mouse model freely available through a sample repository, so researchers can obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens. Experimental design: Twelve datasets are available, encompassing 841 LC-MS/MS experiments (plasma and tissues) and 255 microarray analyses of multiple tissues (thymus, spleen, liver, blood cells, and breast). Cases and controls were rigorously paired to avoid bias. Results: In total, 18,880 unique peptides were identified (PeptideProphet peptide error rate â¤1%), with 3884 and 1659 non-redundant protein groups identified in plasma and tissue datasets, respectively. Sixty-one of these protein groups overlapped between cancer plasma and cancer tissue. Conclusions and clinical relevance: These data are of use for advancing our understanding of cancer biology, for software and quality control tool development, investigations of analytical variation in MS/MS data, and selection of proteotypic peptides for MRM-MS. The availability of these datasets will contribute positively to clinical proteomics. Custom Agilent 44K whole mouse genome expression oligonucleotide microarrays were used to profile breast tumors from three Her2/Neu mice compared to normal breast epithelium from two control mice transgenic for TetO-NeuNT only and littermates of the bitransgenic mice. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference pool of normal adult mouse tissues.
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2011-01-15 | GSE12622 | GEO