IPA: Integrated Predictive Gene Signature from Gene Expression based Breast Cancer Patient Samples

Background: Novel predictive markers are needed to accurately diagnose the breast cancer patients so they do not need to undergo any unnecessary aggressive therapies. Various gene expression studies based predictive gene signatures have generated in the recent past to predict the binary estrogen-receptor subclass or to predict the therapy response subclass. However, the existing algorithms comes with many limitations, including low predictive performances over multiple cohorts of patients and non-significant or limited biological roles associated with the predictive gene signatures. Therefore, the aim of this study is to develop novel predictive markers with improved performances. Methods: We propose a novel prediction algorithm called IPA to construct a predictive gene signature for performing multiple prediction tasks of predicting estrogen-receptor based binary subclass and predicting chemotherapy response (neoadjuvantly) based binary subclass. The constructed gene signature with considering multiple classification techniques was used to evaluate the algorithm performance on multiple cohorts of breast cancer patients. Results: The evaluation on multiple validation cohorts demonstrated that proposed algorithm achieved stable and high performance to perform prediction tasks, with consideration given to any classification techniques. We show that the predictive gene signature of our proposed algorithm reflects the mechanisms underlying the estrogen-receptors or response to therapy with significant greater biological interpretations, compared with the other existing algorithm.