Non-small Cell Lung Cancer Survival Estimation Through Multi-omic Two-layer SVM: A Multi-omics and Multi-Sources Integrative Model

Background The new paradigm of precision medicine brought an increasing interest in survival prediction based on the integration of multi-omics and multi-sources data. Several models have been developed to address this task, but their performances are widely variable depending on the specific disease and are often poor on noisy datasets, such as in the case of non-small cell lung cancer (NSCLC).Objective The aim of this work is to introduce a novel computational approach, named multi-omic two-layer SVM (mtSVM), and to exploit it to get a survival-based risk stratification of NSCLC patients from an ongoing observational prospective cohort clinical study named PROMOLE.Methods The model implements a model-based integration by means of a two-layer feed-forward network of FastSurvivalSVMs, and it can be used to get individual survival estimates or survival-based risk stratification. Despite being designed for NSCLC, its range of applicability can potentially cover the full spectrum of survival analysis problems where integration of different data sources is needed, independently of the pathology considered.Results The model is here applied to the case of NSCLC, and compared with other state-of-the-art methods, proving excellent performance. Notably, the model, trained on data from The Cancer Genome Atlas (TCGA), has been validated on an independent cohort (from the PROMOLE study), and the results were consistent. Gene-set enrichment analysis of the risk groups, as well as exome analysis, revealed well-defined molecular profiles, such as a prognostic mutational gene signature with potential implications in clinical practice.