Plasma proteomic profiles identify biomarkers predicting Crohn’s disease up to 16 years before onset

Year: 2025

Type: article

Abstract: Reliable tools for early identification of Crohn's disease (CD) remain lacking. We analyzed 2736 plasma proteins in 39,634 UK Biobank (UKB) participants and identified 44 associated with incident CD. CD274, CHI3L1, REG1B, ITGAV, PRSS8, ITGA11, GDF15, DEFA1_DEFA1B, and IL6 ranked highest in protein importance ordering. A machine learning model based on these 9 proteins achieved high prediction for CD in a geographically distinct UKB testing cohort (n = 13,262, AUC 0.76), outperforming clinical risk models. It was externally validated in EPIC-Norfolk (n = 2944, AUC 0.73) and exhibited high discriminatory capacity for CD in the cross-sectional Southern China cohort (n = 74, AUC 0.79). In the UKB testing cohort, combining proteins with clinical data improved predictive performance (AUC 0.78) up to 16 years pre-diagnosis. In the same cohort, individuals at high risk stratified by the protein model were 4.23 times more likely to develop CD. Our findings highlight proteomics-based models as a promising approach to predict CD up to 16 years before diagnosis, offering opportunities for early screening and intervention.

Source: Nature Communications

DOI: 10.1038/s41467-025-66483-4

Authors: Jing Feng, Shuo Chen, Qinming Li, Yu Long, Yuying Ma, Lijun Zhang, Ruijie Zeng, Dongling Luo, Meijun Meng, Shiyi Yu, Chunling Chen, Yanjun Wu, Wentao Huang, Han Zhang, Lingyi Li, Felix W. Leung, Chongyang Duan, Weihong Sha, Hao Chen

Institutions: Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Southern Medical University, South China University of Technology, Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, University of Hong Kong, Nanfang Hospital, University of California, Los Angeles, VA Sepulveda Ambulatory Care Center, VA Greater Los Angeles Healthcare System, Shantou University Medical College

Language: English

Topic: Inflammatory Bowel Disease

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,990

Funders: American Society for Gastrointestinal Endoscopy, Cancer Research UK, National Natural Science Foundation of China, Southern Medical University, Guangdong Provincial People's Hospital, Medical Research Council, Natural Science Foundation of Guangdong Province for Distinguished Young Scholars, Basic and Applied Basic Research Foundation of Guangdong Province

OpenAlex ID: W4417277769