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Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

Protein expression based multimarker analysis of breast cancer samples

Authors: Angela P Presson, Nam K Yoon, Lora Bagryanova, Vei Mah, Mohammad Alavi, Erin L Maresh, Ayyappan K Rajasekaran, Lee Goodglick, David Chia, Steve Horvath

Published in: BMC Cancer | Issue 1/2011

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Abstract

Background

Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. For example, breast cancer TMA data have led to the identification of several promising prognostic markers of survival time. Several studies have shown that TMA data can also be used to cluster patients into clinically distinct groups. Here we use breast cancer TMA data to cluster patients into distinct prognostic groups.

Methods

We apply weighted correlation network analysis (WGCNA) to TMA data consisting of 26 putative tumor biomarkers measured on 82 breast cancer patients. Based on this analysis we identify three groups of patients with low (5.4%), moderate (22%) and high (50%) mortality rates, respectively. We then develop a simple threshold rule using a subset of three markers (p53, Na-KATPase-β1, and TGF β receptor II) that can approximately define these mortality groups. We compare the results of this correlation network analysis with results from a standard Cox regression analysis.

Results

We find that the rule-based grouping variable (referred to as WGCNA*) is an independent predictor of survival time. While WGCNA* is based on protein measurements (TMA data), it validated in two independent Affymetrix microarray gene expression data (which measure mRNA abundance). We find that the WGCNA patient groups differed by 35% from mortality groups defined by a more conventional stepwise Cox regression analysis approach.

Conclusions

We show that correlation network methods, which are primarily used to analyze the relationships between gene products, are also useful for analyzing the relationships between patients and for defining distinct patient groups based on TMA data. We identify a rule based on three tumor markers for predicting breast cancer survival outcomes.
Appendix
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Metadata
Title
Protein expression based multimarker analysis of breast cancer samples
Authors
Angela P Presson
Nam K Yoon
Lora Bagryanova
Vei Mah
Mohammad Alavi
Erin L Maresh
Ayyappan K Rajasekaran
Lee Goodglick
David Chia
Steve Horvath
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-230

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