ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1606874
This article is part of the Research TopicAdvanced Machine Learning Techniques in Cancer Prognosis and ScreeningView all 3 articles
Integrated multi-omics and machine learning reveal an immunogenic cell death-related signature for prognostic stratification and therapeutic optimization in colorectal cancer
Provisionally accepted
- 1School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou, China
- 2Suzhou Industrial Park Institute of Services Outsourcing, Suzhou, China
- 3Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Liaoning Province, China
- 4Center for Systems Biology, Soochow University, Suzhou, Jiangsu Province, China
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Colorectal cancer (CRC) continues to rise in global incidence and remains a leading cause of cancerrelated mortality. Immunogenic cell death (ICD) has emerged as a critical modulator of tumor microenvironment (TME) dynamics; however, its prognostic implications and therapeutic potential in CRC require systematic characterization. Through the integrative analysis of single-cell RNA sequencing and bulk transcriptomic data, 11 ICD-related genes with prognostic significance were identified in CRC. A comprehensive computational framework was then employed to evaluate 101 machine learning combinations, ultimately constructing an optimized 11-gene ICD-related signature (ICDRS) by integrating StepCox [forward] and RSF. The ICDRS exhibited strong predictive performance for overall survival in CRC patients across the training and validation datasets. Notably, the ICDRS-based nomogram achieved outstanding time-dependent AUCs (>0.90)for 1-to 3-year survival prediction. Multidimensional analysis revealed significant associations between ICDRS-derived risk score and distinct immune infiltration patterns, immunotherapy response and TME characteristics. Furthermore, a novel macrophage subtype, SPP1 + /SLC11A1 + , was discovered and characterized by high infiltration levels. Drug repurposing analysis indicated Olaparib as a potential therapeutic candidate for high-risk CRC patients. Therefore, this study establishes ICDRS as a promising tool for CRC prognosis and immunotherapy, with future validation studies planned to guide personalized treatment strategies.
Keywords: colorectal cancer, single-cell RNA sequencing, Immunogenic cell death, macrophage, Immunotherapy
Received: 06 Apr 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Hou, Heng, Xie, Zhao, Chen, Yu, Lin and Qi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yuxin Lin, Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Liaoning Province, China
Xin Qi, School of Chemistry and Life Sciences, Suzhou University of Science and Technology, Suzhou, China
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