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Exploring the prognostic role of senescence-related genes in gastric cancer through multi-omics integration and machine learning

Hum Genomics. 2026 May 9. doi: 10.1186/s40246-026-00979-y. Online ahead of print.

ABSTRACT

Cellular senescence plays a context-dependent role in gastric cancer (GC), functioning both through tumor-suppressive arrest and the tumor-promoting senescence-associated secretory phenotype. However, its systematic integration into prognostic models remains limited. Here, we develop a novel interpretable framework to identify and validate a robust senescence-related gene signature for GC prognosis. We first introduce a dual-model interpretable feature selection strategy that integrates a biologically informed Kolmogorov-Arnold Network with a tabular foundation model to identify cancer-associated senescence genes. From the initial candidates, an ensemble of ten machine learning algorithms distills a core 4-gene signature to construct a Senescence Risk Score (SRS). The SRS proves to be a powerful and independent prognostic indicator, effectively stratifies patients into high- and low-risk groups with distinct overall survival across multiple cohorts. High-risk patients exhibit an "immune-hot" but potentially dysfunctional tumor microenvironment, characterized by enriched immune cell infiltration, elevated checkpoint expression, and distinct metabolic reprogramming favoring pathways such as angiogenesis and epithelial-mesenchymal transition (EMT). Furthermore, the SRS correlates with differential somatic mutation profiles and suggests potential sensitivity to specific chemotherapeutic agents. In vitro functional assays confirmed the oncogenic role of SERPINE1, a top-ranked core gene, in promoting GC cell proliferation. Regulatory network analysis revealed potential upstream transcription factors and miRNAs governing the signature. Collectively, we present a validated senescence-related prognostic signature that enables effective risk stratification of patients with gastric cancer.

PMID:42106891 | DOI:10.1186/s40246-026-00979-y

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WoVR: World Models as Reliable Simulators for Post-Training VLA Policies with RL

arXiv:2602.13977v1 Announce Type: cross Abstract: Reinforcement learning (RL) promises to unlock capabilities beyond imitation learning for Vision-Language-Action (VLA) models, but its requirement for massive real-world interaction prevents direct deployment on physical robots. Recent work attempts to use learned world models as simulators for policy optimization, yet closed-loop imagined rollouts inevitably suffer from hallucination and long-horizon error accumulation. Such errors do not merely degrade visual fidelity; they corrupt the optimization signal, encouraging policies to exploit model inaccuracies rather than genuine task progress. We propose WoVR, a reliable world-model-based reinforcement learning framework for post-training VLA policies. Instead of assuming a faithful world model, WoVR explicitly regulates how RL interacts with imperfect imagined dynamics. It improves rollout stability through a controllable action-conditioned video world model, reshapes imagined interaction to reduce effective error depth via Keyframe-Initialized Rollouts, and maintains policy-simulator alignment through World Model-Policy co-evolution. Extensive experiments on LIBERO benchmarks and real-world robotic manipulation demonstrate that WoVR enables stable long-horizon imagined rollouts and effective policy optimization, improving average LIBERO success from 39.95% to 69.2% (+29.3 points) and real-robot success from 61.7% to 91.7% (+30.0 points). These results show that learned world models can serve as practical simulators for reinforcement learning when hallucination is explicitly controlled.
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