Abstract
BackgroundTissue 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.MethodsWe 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.ResultsWe 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.ConclusionsWe 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.
Highlights
Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers
We present results from applying weighted correlation network analysis (WGCNA) to a breast cancer data set consisting of 26 markers measured on 82 patients
Evaluate the utility of WGCNA groups for survival prediction To understand the clinical meaning of the three patient clusters we studied the relationships between the groups and clinical variables
Summary
Tissue microarray (TMA) data are commonly used to validate the prognostic accuracy of tumor markers. We use breast cancer TMA data to cluster patients into distinct prognostic groups. High-density breast tissue microarrays (TMA) and proteomics data have been useful for prognosticating cancer outcomes [5,7]. A common workflow is to identify candidate markers using gene expression arrays and to validate the prognostic accuracy of corresponding protein measures using a TMA platform. We use correlation networks to classify patients into distinct survival groups. We develop a prognostic rule (referred to as WGCNA*) based on a subset of markers that can be used to classify patients into distinct survival groups. We validate the prognostic accuracy of this rule in two independent Affymetrix HG-U133A gene expression data sets
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