Predicting Treatment Outcomes in Patients with Low Back Pain Using Gene Signature-Based Machine Learning Models

Introduction: Low back pain (LBP) is a significant global health burden, with variable treatment outcomes and an unclear underlying molecular mechanism. Effective prediction of treatment responses remains a challenge. In this study, we aimed to develop gene signature-based machine learning models using transcriptomic data from peripheral immune cells to predict treatment outcomes in patients with LBP. Methods: The transcriptomic data of patients with LBP from peripheral immune cells were retrieved from the GEO database. Patients with LBP were recruited, and treatment outcomes were assessed after 3 months. Patients were classified into two groups: those with resolved pain and those with persistent pain. Differentially expressed genes (DEGs) between the two groups were identified through bioinformatic analysis. Key genes were selected using five machine learning models, including Lasso, Elastic Net, Random Forest, SVM, and GBM. These key genes were then used to train 45 machine learning models by combining nine different algorithms: Logistic Regression, K-Nearest Neighbors, Support Vector Machine, Decision Tree, Random Forest, Gradient Boosting Machine, Multilayer Perceptron, Naive Bayes, and Linear Discriminant Analysis. Five-fold cross-validation was employed to ensure robust model evaluation and minimize overfitting. In each fold, the dataset was split into training and validation sets, with model performance assessed using multiple metrics including accuracy, precision, recall, and F1 score. The final model performance was reported as the mean and standard deviation across all five folds, providing a more reliable estimate of the models' ability to predict LBP treatment outcomes using gene expression data from peripheral immune cells. Results: A total of 61 DEGs were identified between patients with resolved and persistent pain. From these genes, 45 machine learning models were constructed using different combinations of feature selection methods and classification algorithms. The Elastic Net with Logistic Regression achieved the highest accuracy of 88.7% +/- 8.0% (mean +/- standard deviation), followed closely by Elastic Net with Linear Discriminant Analysis (88.7% +/- 7.5%) and Lasso with Multilayer Perceptron (87.7% +/- 6.7%). Overall, 15 models demonstrated robust performance with accuracy > 80%, suggesting the reliability of our machine learning approach in predicting LBP treatment outcomes. The SHapley Additive exPlanations (SHAP) method was used to visualize the contribution of core genes to model performance, highlighting their roles in predicting treatment outcomes. Conclusion: The study demonstrates the potential of using transcriptomic data from peripheral immune cells and machine learning models to predict treatment outcomes in patients with LBP. The identification of key genes and the high accuracy of certain models provide a basis for future personalized treatment strategies in LBP management. Visualizing gene importance with SHAP adds interpretability to the predictive models, enhancing their clinical relevance.