Sample-specific network analysis identifies gene co-expression patterns of immunotherapy response in clear cell renal cell carcinoma.

Immunotherapies have recently emerged as a standard of care for advanced cancers, offering remarkable improvements in patient prognosis. However, only a small subset of patients benefit, and robust molecular predictors remain elusive. We present a computational framework leveraging sample-specific gene co-expression networks to identify features predictive of immunotherapy response in kidney cancer. Our results reveal that patients with similar clinical outcomes exhibit comparable gene co-expression patterns. Notably, increased gene connectivity and stronger negative gene-gene associations are hallmarks of poor responders. We further developed sample-specific pathway-level network scores to detect dysregulated biological pathways linked to treatment outcomes. Finally, incorporating these sample-level network features improves the predictive performance of gene expression-based machine learning models. This work highlights the value of personalized gene network features for stratifying patients with cancer and optimizing immunotherapy strategies.