Serum Proteomics Reveals Diagnostic Biomarkers and Molecular Pathways in Cerebral Palsy

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.

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Publication Details

Journal
Nature Communications
Published
2025-11-21
DOI
https://doi.org/10.1038/s41467-025-65110-6
Primary Topic
Cerebral Palsy and Movement Disorders
Type
article
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article

Serum Proteomics Reveals Diagnostic Biomarkers and Molecular Pathways in Cerebral Palsy

Qinghe Xing, Chi Ma, Yangong Wang, Jozef Gécz et al.
Nature Communications
Cerebral Palsy and Movement Disorders
article

Serum Proteomics Reveals Diagnostic Biomarkers and Molecular Pathways in Cerebral Palsy

Qinghe Xing, Chi Ma, Yangong Wang, Jozef Gécz, Hui Gao, Jinwen Feng, Dengna Zhu, Subei Tan, Michael C. Kruer, Sha Tian, Yanan Wu, Yiran Xu, Yanyan Sun, Xiaoyang Wang, Lingling Zhang, Xiaoli Zhang, Chen Ding, Shiman He, Jiamei Zhang, Jiajun Zhu, Lirong Zhang, Changlian Zhu
article en

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.

Nature CommunicationsVol. 16(1)
Barrow Neurological Institute (US), University of Arizona (US), Fudan University (CN), Karolinska Institutet (SE), Zhengzhou University (CN), Pudong Medical Center (CN), Third Affiliated Hospital of Zhengzhou University (CN), Children's Hospital of Fudan University (CN), The University of Adelaide (AU), University of Gothenburg (SE)
Openalex Percentile: Top 58%
Cerebral Palsy and Movement Disorders
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