Serum Proteomics Reveals Diagnostic Biomarkers and Molecular Pathways in Cerebral Palsy

Yiran Xu, Chi Ma, Yanyan Sun, Jiajun Zhu, Shiman He, Hui Gao, Subei Tan, Lingling Zhang, Jinwen Feng, Yangong Wang, Sha Tian, Qinghe Xing, Jiamei Zhang, Yanan Wu, Xiaoli Zhang, Lirong Zhang, Dengna Zhu, Michael Kruer, Xiaoyang Wang, Jozef Gecz, Changlian Zhu () and Chen Ding ()
Additional contact information
Yiran Xu: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Chi Ma: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute
Yanyan Sun: Zhengzhou University, Department of Human Anatomy, School of Basic Medicine
Jiajun Zhu: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute
Shiman He: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute
Hui Gao: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Subei Tan: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute
Lingling Zhang: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Jinwen Feng: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute
Yangong Wang: Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University
Sha Tian: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute
Qinghe Xing: Children’s Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University
Jiamei Zhang: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Yanan Wu: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Xiaoli Zhang: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Lirong Zhang: Zhengzhou, Department of Pharmacology, School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University
Dengna Zhu: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Michael Kruer: Phoenix Children’s Hospital, Pediatric Movement Disorders Program, Barrow Neurological Institute
Xiaoyang Wang: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Jozef Gecz: The University of Adelaide, Robinson Research Institute and Adelaide Medical School
Changlian Zhu: The Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center
Chen Ding: Fudan University, Clinical Research Center for Cell-based Immunotherapy of Shanghai Pudong Hospital, Fudan University Pudong Medical Center, State Key Laboratory of Genetics and Development of Complex Phenotypes, School of Life Sciences, Human Phenome Institute

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Cerebral palsy (CP), a prevalent non-progressive neurological disorder in children, lacks reliable biomarkers for early diagnosis, and its molecular mechanisms remain poorly understood. In this study, we conducted serum proteomic profiling of 346 CP patients and 190 healthy controls and developed a 10-protein multi-marker panel for application in diagnosis of CP. The panel was further validated in an independent CP cohort using an orthogonal method, enzyme-linked immunosorbent assay (ELISA). By integrating serum proteomic data with whole-exome sequencing (WES) results, we found that CP patients carrying pathogenic variants exhibited downregulation of synaptic and calcium signaling pathways at the protein level. We also explored the impact of clinical risk factors on the proteome, identifying disruptions in lipid metabolism associated with low birth weight and low gestational age. Additionally, we found a positive correlation between Immunoglobulin Heavy Variable (IGHV) families and higher Gross Motor Function Classification System (GMFCS) levels. Overall, our study provides a valuable tool for early CP diagnosis that complements standard clinical and genomic assessments, and suggests potential molecular mechanisms associated with CP pathogenesis, highlighting the interplay among genetic, environmental, and protein network factors.

Date: 2025
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DOI: 10.1038/s41467-025-65110-6

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