Optimizing Prognostic Biomarker Discovery in Pancreatic Cancer Through Hybrid Ensemble Feature Selection and Multi-Omics Data

Prediction of patient survival using high-dimensional multi-omics data requires systematic feature selection methods that ensure predictive performance, sparsity, and reliability for prognostic biomarker discovery. We developed a hybrid ensemble feature selection (hEFS) approach that combines data subsampling with multiple prognostic models, integrating both embedded and wrapper-based strategies for survival prediction. Omics features are ranked using a voting-theory-inspired aggregation mechanism across models and subsamples, while the optimal number of features is selected via a Pareto front, balancing predictive accuracy and model sparsity without any user-defined thresholds. When applied to multi-omics datasets from three pancreatic cancer cohorts, hEFS identifies significantly fewer and more stable biomarkers compared to the conventional, late-fusion CoxLasso models, while maintaining comparable discrimination performance. Implemented within the open-source mlr3fselect R package, hEFS offers a robust, interpretable, and clinically valuable tool for prognostic modelling and biomarker discovery in high-dimensional survival settings.