Abstract
BackgroundPrevious studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+.ResultsBased upon the analysis of 599 microarrays (five separate cDNA microarray datasets) using a novel approach, we present evidence in support of the most consistently identifiable subtypes of breast cancer tumor tissue microarrays being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2 subtypes). We validate all three subtypes statistically and show the subtype to which a sample belongs is a significant predictor of overall survival and distant-metastasis free probability.ConclusionAs a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID) to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.
Highlights
Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles
We show which of the three subtypes a sample belonged to was a significant predictor of overall survival and distant metastasis-free probability in the validation dataset for which we had clinical data
Of the pairs of genes which resulted in four sample groups that were all validated in the training dataset, no pair's groups were validated at the α = 0.05 significance level in all of the validation datasets
Summary
Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+. Perou et al (2000) reported evidence for breast cancer tumor subtypes defined by gene expression patterns. From the results of hierarchical clustering of 65 breast cancer and normal breast samples based on their pattern of expression of 496 intrinsic genes, Perou et al (2000) defined four groups: basal-like, Erb-B2 +, normal-breastlike, and luminal epithelial/ER+. Sørlie et al (2001) retained the basal-like, Erb-B2+ (re-named ERBB2+ in Sørlie et al (2001)), and normal-breast-like groups but divided the luminal epithelial/ER+ group into three subtypes: luminal A, luminal B, and luminal C. All six groups were found in the second dataset and differences in overall survival between the five groups (ERBB2+ and luminal B were combined) were significant [2]
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