Inflammatory bowel diseases · 2026
Novel proteomic signatures of stricturing Crohn disease using a treatment-naive cohort.
СтатьяНазвание и аннотация: Перевод в очереди
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Liu Zishan, Wu Xiaomin, Huang Weidong, He Jinshen, Wang Yu, Gu Tingting, Chen Baili, He Yao, Zeng Zhirong, Zhang Yao, Cao Qian, Haberman Yael, Chen Minhu, Feng Rui, Hu Shixian, Wang Guibin, Mao Ren
Аннотация
BACKGROUND: Crohn disease (CD) is frequently complicated by intestinal strictures, which require early recognition and management. This study aimed to identify biomarkers associated with CD-related strictures by use of serum and intestinal proteomics and to develop diagnostic and predictive models for potential clinical application.
METHODS: Serum samples from treatment-naive CD patients and paired intestinal samples from stricturing intestine were subjected to proteomic analysis. Machine learning approaches were employed to select stricture-related biomarkers and develop models. The candidate protein was validated using external cohorts and molecular experiments.
RESULTS: The discovery cohort included 62 patients. A diagnostic model for intestinal stricture was developed using serum levels of 5 proteins from 30 nonstricturing, nonpenetrating (B1) phenotype and 20 stricturing (B2) phenotype patients, achieving an area under the curve of 0.754. A predictive model for stricture progression, based on another set of 5 proteins in 10 B1 progressors, achieved an AUC of 0.947 internally. Serum enzyme-linked immunoassay (ELISA) validation in the First Affiliated Hospital of Sun Yat-sen University (FAH-SYSU) and Sir Run Run Shaw Hospital (SRRSH) cohorts (n = 62) confirmed elevated glypican-6 (GPC6) levels in the stricturing (B2) group, with a similar trend observed in intestinal tissue in the progression group of the RISK cohort (n = 237). Single-cell transcriptomic analysis and immunofluorescence staining further confirmed higher GPC6 expression and protein levels in the fibrostenotic mucosa and submucosa, particularly in fibroblasts.
CONCLUSIONS: We developed serum-based diagnostic and predictive models for intestinal strictures in CD, which may be suitable for clinical use once externally adequately validated. GPC6 emerged as a candidate biomarker closely associated with intestinal fibrosis, offering promising implications for its diagnosis and prognosis.
METHODS: Serum samples from treatment-naive CD patients and paired intestinal samples from stricturing intestine were subjected to proteomic analysis. Machine learning approaches were employed to select stricture-related biomarkers and develop models. The candidate protein was validated using external cohorts and molecular experiments.
RESULTS: The discovery cohort included 62 patients. A diagnostic model for intestinal stricture was developed using serum levels of 5 proteins from 30 nonstricturing, nonpenetrating (B1) phenotype and 20 stricturing (B2) phenotype patients, achieving an area under the curve of 0.754. A predictive model for stricture progression, based on another set of 5 proteins in 10 B1 progressors, achieved an AUC of 0.947 internally. Serum enzyme-linked immunoassay (ELISA) validation in the First Affiliated Hospital of Sun Yat-sen University (FAH-SYSU) and Sir Run Run Shaw Hospital (SRRSH) cohorts (n = 62) confirmed elevated glypican-6 (GPC6) levels in the stricturing (B2) group, with a similar trend observed in intestinal tissue in the progression group of the RISK cohort (n = 237). Single-cell transcriptomic analysis and immunofluorescence staining further confirmed higher GPC6 expression and protein levels in the fibrostenotic mucosa and submucosa, particularly in fibroblasts.
CONCLUSIONS: We developed serum-based diagnostic and predictive models for intestinal strictures in CD, which may be suitable for clinical use once externally adequately validated. GPC6 emerged as a candidate biomarker closely associated with intestinal fibrosis, offering promising implications for its diagnosis and prognosis.