Integration of multiple machine learning approaches develops a gene mutation-based classifier for accurate immunotherapy outcomes

Shi, Run; Sun, Jing; Zhou, Zhaokai; Shi, Meiqi; Wang, Xin; Gao, Zhaojia; Zhao, Tianyu; Li, Minglun und Shu, Yongqian (27. Februar 2025): Integration of multiple machine learning approaches develops a gene mutation-based classifier for accurate immunotherapy outcomes. In: npj Precision Oncology, Bd. 9, Nr. 54

Abstract

In addition to traditional biomarkers like PD-(L)1 expression and tumor mutation burden (TMB), more reliable methods for predicting immune checkpoint blockade (ICB) response in cancer patients are urgently needed. This study utilized multiple machine learning approaches on nonsynonymous mutations to identify key mutations that are most significantly correlated to ICB response. We proposed a classifier, Gene mutation-based Predictive Signature (GPS), to categorize patients based on their predicted response and clinical outcomes post-ICB therapy. GPS outperformed conventional predictors when validated in independent cohorts. Multi-omics analysis and multiplex immunohistochemistry (mIHC) revealed insights into tumor immunogenicity, immune responses, and the tumor microenvironment (TME) in lung adenocarcinoma (LUAD) across different GPS groups. Finally, we validated distinct responses of different GPS samples to ICB in an ex-vivo tumor organoid-PBMC co-culture model. Overall, our findings highlight a simple, robust classifier for accurate ICB response prediction, which could reduce costs, shorten testing times, and facilitate clinical implementation.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Institut und Poliklinik für Arbeits-, Sozial- und Umweltmedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2397-768X
• Sprache: Englisch