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A machine learned classifier that uses gene expression data to accurately predict estrogen receptor status.

ABSTRACT: BACKGROUND: Selecting the appropriate treatment for breast cancer requires accurately determining the estrogen receptor (ER) status of the tumor. However, the standard for determining this status, immunohistochemical analysis of formalin-fixed paraffin embedded samples, suffers from numerous technical and reproducibility issues. Assessment of ER-status based on RNA expression can provide more objective, quantitative and reproducible test results. METHODS: To learn a parsimonious RNA-based classifier of hormone receptor status, we applied a machine learning tool to a training dataset of gene expression microarray data obtained from 176 frozen breast tumors, whose ER-status was determined by applying ASCO-CAP guidelines to standardized immunohistochemical testing of formalin fixed tumor. RESULTS: This produced a three-gene classifier that can predict the ER-status of a novel tumor, with a cross-validation accuracy of 93.17±2.44%. When applied to an independent validation set and to four other public databases, some on different platforms, this classifier obtained over 90% accuracy in each. In addition, we found that this prediction rule separated the patients' recurrence-free survival curves with a hazard ratio lower than the one based on the IHC analysis of ER-status. CONCLUSIONS: Our efficient and parsimonious classifier lends itself to high throughput, highly accurate and low-cost RNA-based assessments of ER-status, suitable for routine high-throughput clinical use. This analytic method provides a proof-of-principle that may be applicable to developing effective RNA-based tests for other biomarkers and conditions.

SUBMITTER: Bastani M

PROVIDER: S-EPMC3846850 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Project description:BackgroundLong non-coding RNAs (lncRNAs), which have little or no ability to encode proteins, have attracted special attention due to their potential role in cancer disease. In this study we aimed to establish a lncRNAs classifier to improve the accuracy of recurrence prediction for thymic epithelial tumors (TETs).MethodsTETs RNA sequencing (RNA-seq) data set and the matched clinicopathologic information were downloaded from the Cancer Genome Atlas. Using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, we developed a lncRNAs classifier related to recurrence. Functional analysis was conducted to investigate the potential biological processes of the lncRNAs target genes. The independent prognostic factors were identified by Cox regression model. Additionally, predictive ability and clinical application of the lncRNAs classifier were assessed, and compared with the Masaoka staging by receiver operating characteristic (ROC) analysis and decision curve analysis (DCA).ResultsFour recurrence-free survival (RFS)-related lncRNAs were identified, and the classifier consisting of the identified four lncRNAs was able to effectively divide the patients into high and low risk subgroups, with an area under curve (AUC) of 0.796 (three-year RFS) and 0.788 (five-year RFS), respectively. Multivariate analysis indicated that the lncRNAs classifier was an independent recurrence risk factor. The AUC of the lncRNAs classifier in predicting RFS was significantly higher than the Masaoka staging system. Decision curve analysis further demonstrated that the lncRNAs classifier had a larger net benefit than the Masaoka staging system.ConclusionsA lncRNAs classifier for patients with TETs was an independent risk factor for RFS despite other clinicopathologic variables. It generated more accurate estimations of the recurrence probability when compared to the Masaoka staging system, but additional data is required before it can be used in clinical practice.

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A machine learned classifier that uses gene expression data to accurately predict estrogen receptor status.

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