2. Academic Validation
  3. Machine Learning-Driven Multi-Omics Analysis Identifies CHP2 as a Key PANoptosis-Related Dual-Function Biomarker in Colorectal Cancer

Machine Learning-Driven Multi-Omics Analysis Identifies CHP2 as a Key PANoptosis-Related Dual-Function Biomarker in Colorectal Cancer

  • Cells. 2026 Feb 28;15(5):430. doi: 10.3390/cells15050430.
Zetian Zhang 1,  Xingyu Jiang 1,  Xin Zhang 1,  Fan Li 1 2 3 4 5
Affiliations

Affiliations

  • 1 The Key Laboratory of Zoonosis, Department of Pathogen Biology, Chinese Ministry of Education, College of Basic Medical Sciences, Jilin University, Changchun 130000, China.
  • 2 The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun 130000, China.
  • 3 Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun 130000, China.
  • 4 Key Laboratory for Health Biomedical Materials of Jilin Province, Jilin University, Changchun 130000, China.
  • 5 State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi 830000, China.
PMID: 41827864 DOI: 10.3390/cells15050430
Abstract

The heterogeneity of colorectal Cancer (CRC) represents a great challenge in therapy. We integrated multiomics and machine learning, interpreted by SHAP models to provide a clinical rationale, to identify Calcineurin B Homologous Protein 2 (CHP2) as a core candidate, which was further validated via in vitro and zebrafish models. The expression of CHP2 are decreased in CRC, which is associated with a poor prognosis and an immune suppressed "cold" TIME. Functionally, CHP2 overexpression inhibits cell growth and invasion by inducing PANoptosis. Clinically, specific CHP2 expression profiles discriminate patients at high risk that are resistant to standard chemotherapy (e.g., 5-FU) but sensitive to targeted inhibitors. CHP2 is a powerful dual-function biomarker-prognostic for survival and predictive for the response to therapy-that could lead to a personalized approach in treating drug-resistant CRC.

Keywords

PANoptosis; calcineurin B homologous protein 2; colorectal cancer; dual-function biomarker; machine learning-driven multiomics analysis; tumor immune microenvironment.

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