Single-Cell Sequencing-Based Validation of T Cell-Associated Diagnostic Model Genes and Drug Response in Crohn’s Disease
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Published:2023-03-23
Issue:7
Volume:24
Page:6054
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Dai Zhujiang12, Zhang Jie3, Xu Weimin12, Du Peng12, Wang Zhongchuan12, Liu Yun12
Affiliation:
1. Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China 2. Shanghai Colorectal Cancer Research Center, Shanghai 200092, China 3. Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
Abstract
Crohn’s disease is a highly heterogeneous autoimmune disease with a unique inflammatory phenotype of T cells at the lesion site. We aim to further explore the diagnosis of Crohn’s disease and drug prediction of T cell marker gene expression. We obtained single-cell expression profile data from 22 CDs or normal samples and performed cell annotation and cellular communication analysis. Through the intersection of T cell marker genes, differential genes, and WGCNA results, we identified T cell-specific key genes and their immune landscapes and potential pathogenesis, and validated them across multiple datasets and patient tissue samples. We also explored the differentiation characteristics of genes by pseudo-temporal analysis and assessed their diagnostic performance and drug sensitivity by molecular docking. Finally, we extended this study to the prognosis of IBD-associated colon cancer. TNF-centered 5-gene diagnostic model not only has excellent diagnostic efficacy, but is also closely associated with KRAS, P53, and IL6/JAK/STAT3 pathways and physiological processes, such as EMT, coagulation, and apoptosis. In addition, this diagnostic model may have potential synergistic immunotherapeutic effects, with positive correlations with immune checkpoints such as CTLA4, CD86, PDCD1LG2, and CD40. Molecular docking demonstrated that BIRC3 and ANXA1 have strong binding properties to Azathioprine and Glucoocorticoid. Furthermore, the 5-gene model may suggest antagonism to IFX and prognosis for colon cancer associated with inflammatory bowel disease. Single-cell sequencing targeting T cell-related features in patients with Crohn’s disease may aid in new diagnostic decisions, as well as the initial exploration of high-potential therapies.
Funder
National Natural Science Foundation of China Shanghai Sailing Program Qingfeng Scientific Research Fund of the China Crohn’s & Colitis Foundation Shanghai Pujiang Talent Program
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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