iMLGAM: Integrated Machine Learning and Genetic Algorithm‐driven Multiomics analysis for pan‐cancer immunotherapy response prediction
To address the substantial variability in immune checkpoint blockade (ICB) therapy effectiveness, we developed an innovative R package called integrated Machine Learning and Genetic Algorithm-driven Multiomics analysis (iMLGAM), which establishes a comprehensive scoring system for predicting treatment outcomes through advanced multi-omics data integration. Our research demonstrates that iMLGAM scores exhibit superior predictive performance across independent cohorts, with lower scores correlating significantly with enhanced therapeutic responses and outperforming existing clinical biomarkers. Detailed analysis revealed that tumors with low iMLGAM scores display distinctive immune microenvironment characteristics, including increased immune cell infiltration and amplified antitumor immune responses. Critically, through clustered regularly interspaced short palindromic repeats screening, we identified Centrosomal Protein 55 (<i>CEP55</i>) as a key molecule modulating tumor immune evasion, mechanistically confirming its role in regulating T cell-mediated antitumor immune responses. These findings not only validate iMLGAM as a powerful prognostic tool but also propose <i>CEP55</i> as a promising therapeutic target, offering novel strategies to enhance ICB treatment efficacy. The iMLGAM package is freely available on GitHub (https://github.com/Yelab1994/iMLGAM), providing researchers with an innovative approach to personalized cancer immunotherapy prediction.
Authors
- Jiaxiong Tan (ORCID: https://orcid.org/0000-0002-5606-3962)
- Songyun Zhao (ORCID: https://orcid.org/0000-0003-0542-1085)
- Xiaoqing Liang (ORCID: https://orcid.org/0000-0003-1992-9592)
- Peng Luo (ORCID: https://orcid.org/0000-0002-8215-2045)
- Chuanli Ren (ORCID: https://orcid.org/0000-0002-8386-3586)
- Jiaheng Xie (ORCID: https://orcid.org/0000-0002-4992-498X)
- Wenhang Zhou
- Aimin Jiang (ORCID: https://orcid.org/0000-0002-4092-342X)
- Bicheng Ye
- Zhuang Yu (ORCID: https://orcid.org/0000-0003-1676-135X)
- Haoran Lin (ORCID: https://orcid.org/0009-0002-2776-5487)
- Pengpeng Zhang (ORCID: https://orcid.org/0000-0003-1488-265X)
- Qifan Li (ORCID: https://orcid.org/0000-0001-5296-474X)
- Lei Xue (ORCID: https://orcid.org/0000-0002-1951-4322)
- Jun Fan
Institutions
- Central South University (CN)
- Xuzhou Medical College (CN)
- Second Military Medical University (CN)
- Wenzhou Medical University (CN)
- First Affiliated Hospital of Wenzhou Medical University (CN)
- Tianjin Medical University Cancer Institute and Hospital (CN)
- Soochow University (CN)
- Zhongda Hospital Southeast University (CN)
- Nanjing Brain Hospital (CN)
- Changhai Hospital (CN)
- Zhujiang Hospital (CN)
- Second People’s Hospital of Huai’an (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Northern Jiangsu People's Hospital (CN)
- Nanjing Chest Hospital (CN)
- Jiangsu Province Hospital (CN)
- First Affiliated Hospital of Soochow University (CN)
- Xiangya Hospital Central South University (CN)
- Southern Medical University (CN)
- Nanjing Medical University (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- iMeta
- Published
- 2025-03-08
- DOI
- https://doi.org/10.1002/imt2.70011
- Citations
- 121
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 126.49
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Jiangsu Province