High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

Abstract

Introduction: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed. Methods: A newly developed machine learning model was applied on several gene expression data from the public repository GEO database to identify molecular signatures predictive of efficacy of 5-FU based combination chemotherapy (FOLFOX and FOLFIRI) in patients with CRC. The model was trained using 5-fold cross validation and multiple feature selection methods including LASSO and VarSelRF methods. Random Forest and support vector machine classifiers were applied to evaluate the performance of the models. Results and Discussion: For the CRC GEO dataset samples from patients who received either FOLFOX or FOLFIRI, validation and test sets were >90% correctly classified (accuracy), with specificity and sensitivity ranging between 85%-95%. In the datasets used from the GEO database, 28.6% of patients who failed the treatment therapy they received are predicted to benefit from the alternative treatment. Analysis of the gene signature suggests the mechanistic difference between colorectal cancers that respond and those that do not respond to FOLFOX and FOLFIRI. Application of this machine learning approach could lead to improvements in treatment outcomes for patients with CRC and other cancers after additional appropriate clinical validation.