Deep Generative and Graph-Based Representation Learning for Multiomics Survival Stratification in Ovarian Cancer:...

Ovarian cancer remains one of the most lethal gynecologic malignancies, largely due to pronounced molecular heterogeneity, nonspecific clinical presentation, and frequent diagnosis at advanced stages. Multiomics profiling-including genomics, transcriptomics, and epigenomics-offers a powerful avenue for characterizing this complexity and enabling more precise patient stratification.

This study aimed to address key challenges in multiomics analysis, including high dimensionality, cross-modality heterogeneity, limited sample size, and the lack of effective approaches for survival stratification of patients with ovarian cancer through deep representation learning.

We analyzed multiomics data from The Cancer Genome Atlas and developed a 5-stage deep learning pipeline centered on variational autoencoders (VAEs) for nonlinear dimensionality reduction and latent representation learning. A graph convolutional neural network component is described as a proposed extension for modeling interaction-aware representations but was not empirically evaluated in this study. Latent embeddings derived from the VAE were clustered using k-means, and their prognostic relevance was assessed using Cox proportional hazards modeling and Kaplan-Meier survival analysis.

Following correction of a clinical-molecular harmonization issue, the final matched cohort comprised 291 patients. Silhouette analysis identified k=2 as the optimal clustering solution (silhouette=0.272). Kaplan-Meier analysis demonstrated significantly different overall survival between the two clusters (log-rank χ²₁=10.0; P=.002). Cox proportional hazards modeling estimated a hazard ratio of 0.519 (95% CI 0.343-0.785; P=.002), indicating that patients assigned to cluster 1 exhibited an approximately 48% lower hazard of death than those in cluster 0. These results demonstrate that the learned latent representations capture prognostically relevant structure within the integrated multiomics data.

The proposed VAE-based framework identified 2 prognostically distinct patient subgroups with significantly different overall survival. These findings demonstrate the potential of deep generative representation learning for multiomics-based survival stratification in ovarian cancer and provide a foundation for future validation in independent cohorts and the evaluation of graph-based extensions.