Dataset Information

Expression data from pure/mixed blood and breast to test feasability of deconvolution of clinical samples

ABSTRACT: Samples collected from human subjects in clinical trials possess a level of complexity, arising from multiple cell types, that can obfuscate the analysis of data derived from them. Blood, for example, contains many different cell types that are derived from a distinct lineage and carry out a different immunological purpose. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies. We used microarrays to detail a statistical approach to model expression from a mixed cell population as the weighted average of expression from different cell types. Consequently, we can accurately and efficiently estimate the abundance of various cell populations. Favoring computation over manual purification has its advantages, such as measuring responses of multiple cell types simultaneously, keeping samples intact, and identifying biologically relevant differentially expressed genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE29832 | GEO | 2011/06/09

SECONDARY ACCESSION(S): PRJNA141003

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Tissues are often made up of multiple cell-types. Blood, for example, contains many different cell-types, each with its own functional attributes and molecular signature. In humans, because of its accessibility and immune functionality, blood cells have been used as a source for RNA-based biomarkers for many diseases. Yet, the proportions of any given cell-type in the blood can vary markedly, even between normal individuals. This results in a significant loss of sensitivity in gene expression studies of blood cells and great difficulty in identifying the cellular source of any perturbations. Ideally, one would like to perform differential expression analysis between patient groups for each of the cell-types within a tissue but this is impractical and prohibitively expensive. To test the relationship between measured gene expression in mixed samples and the expression of genes in the isolated pure subsets, we begin with a situation in which all factors are known. Tissue samples from the brain, liver and lung of a single rat were analyzed using expression arrays (Affymetrix) in triplicate. Homogenates of those three tissues were then mixed together at the cRNA level. We then measured the gene expression pattern of each mixed sample. Such mixtures mimic the common scenario in which biological samples in a dataset are heterogeneous and vary in the relative frequency of the component subsets from one another. We mixed rat brain, liver and lung biospecimens derived from one animal at the cRNA homogenate level in different proportions. 3 technical replicates each. Snap frozen rat liver and brain was kept frozen while cutting it into pieces. cDNA synthesis and labeling was done with a starting amount of 1 Î¼g, using the Affymetrix Eukaryotic One-Cycle Target Hybridization. Washing, Staining and scanning protocol for Eukaryotic Cartridge Arrays with User-Prepared Buffers and Sloutions according to the technical manuals (Affymetrix GeneChip Expression, Analysis for Cartridge Arrays using the GCAS version 1.4, Affymetrix GeneChip Expression Analysis (P/N 701021,Rev. 5) , Affymetrix GeneChip Expression Wash, Stain and Scan (P/N 702731, Rev. 3) , following the manufacturer/s instructions. Data was RMA normalized.

Project description:The Oncotype DX 21-gene test can be used to predict chemotherapy efficacy in patients with estrogen receptor (ER)-positive and HER2-negative breast cancer; however, the data on the 21-gene recurrence score (RS) for mucinous breast carcinoma (MBC) are limited. The present study aimed to evaluate the distribution pattern and clinical value of the 21-gene RS in patients with MBC. A total of 38 pure MBC (PMBC) and 11 mixed MBC (MMBC) cases were retrospectively analyzed, and a total of 29 ER-positive and HER2-negative MBCs underwent the Oncotype DX 21-gene test. There were no statistically significant differences between the PMBCs and MMBCs in age, tumor size and molecular subtype; however, patients with MMBC showed a significantly higher incidence rate of nodal metastases compared with that in patients with PMBC (72.7 vs. 16.2%, respectively). Following surgery, 87.8 and 59.2% of the enrolled patients received endocrine therapy and chemotherapy, respectively. With a median follow-up of 65.6 months, the 5-year disease-free survival and overall survival rates were 97.0 and 100.0%, respectively. The 21-gene test revealed that the proportions of patients with MBC categorized into low (RS <18), intermediate (RS ≥18-30) and high (RS ≥30) risk groups were 51.7, 44.8 and 3.5%, respectively, and there was no statistically significant difference between the PMBC and MMBC cases. Notably, among the genes in the 21-gene RS testing, the expression levels of cathepsin V, progesterone receptor (PR) and CD68 were significantly higher in the PMBC group compared with that in the MMBC group. In conclusion, the current study demonstrated that patients with MBC had a favorable prognosis, and both PMBC and MMBC cases had a low- and intermediate-risk RS, which suggests that a considerable proportion of patients may be able to avoid chemotherapy. In addition, the high expression level of PR, based on the 21-gene test in PMBCs, indicated that they may have a more favorable response to endocrine therapy than MMBCs.

Dataset Information

Expression data from pure/mixed blood and breast to test feasability of deconvolution of clinical samples

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets