Breast cancer stage prediction: a computational approach guided by transcriptome analysis.

Abstract

Breast cancer is the second leading cancer among women in terms of mortality rate. In recent years, its incidence frequency has been continuously rising across the globe. In this context, the new therapeutic strategies to manage the deadly disease attracts tremendous research focus. However, finding new prognostic predictors to refine the selection of therapy for the various stages of breast cancer is an unattempted issue. Aberrant expression of genes at various stages of cancer progression can be studied to identify specific genes that play a critical role in cancer staging. Moreover, while many schemes for subtype prediction in breast cancer have been explored in the literature, stage-wise classification remains a challenge. These observations motivated the proposed two-phased method: stage-specific gene signature selection and stage classification. In the first phase, meta-analysis of gene expression data is conducted to identify stage-wise biomarkers that were then used in the second phase of cancer classification. From the analysis, 118, 12 and 4 genes respectively in stage I, stage II and stage III are determined as potential biomarkers. Pathway enrichment, gene network and literature analysis validate the significance of the identified genes in breast cancer. In this study, machine learning methods were combined with principal component and posterior probability analysis. Such a scheme offers a unique opportunity to build a meaningful model for predicting breast cancer staging. Among the machine learning models compared, Support Vector Machine (SVM) is found to perform the best for the selected datasets with an accuracy of 92.21% during test data evaluation. Perhaps, biomarker identification performed here for stage-specific cancer treatment would be a meaningful step towards predictive medicine. Significantly, the determination of correct cancer stage using the proposed 134 gene signature set can possibly act as potential target for breast cancer therapeutics.