31 94

Cited 0 times in

Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Disease

Authors
 Soo-Kyung Park  ;  Gi-Young Lee  ;  Sangsoo Kim  ;  Chil-Woo Lee  ;  Chang-Hwan Choi  ;  Sang-Bum Kang  ;  Tae-Oh Kim  ;  Jaeyoung Chun  ;  Jae-Myung Cha  ;  Jong-Pil Im  ;  Kwang-Sung Ahn  ;  Seon-Young Kim  ;  Min-Suk Kim  ;  Chang-Kyun Lee  ;  Dong-Il Park 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.24(19) : 14799, 2023-09 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN
 1661-6596 
Issue Date
2023-09
MeSH
Crohn Disease* / drug therapy ; Crohn Disease* / genetics ; Crohn Disease* / metabolism ; Fibroblasts / metabolism ; Humans ; Necrosis / metabolism ; RNA / metabolism ; Tumor Necrosis Factor Inhibitors ; Tumor Necrosis Factor-alpha / genetics ; Tumor Necrosis Factor-alpha / metabolism
Keywords
Crohn’s disease ; RNA sequencing ; activated fibroblasts ; anti-tumor necrosis factor therapy
Abstract
We investigated whether the response to anti-tumor necrosis factor (anti-TNF) treatment varied according to inflammatory tissue characteristics in Crohn's disease (CD). Bulk RNA sequencing (RNA-seq) data were obtained from inflamed and non-inflamed tissues from 170 patients with CD. The samples were clustered based on gene expression profiles using principal coordinate analysis (PCA). Cellular heterogeneity was inferred using CiberSortx, with bulk RNA-seq data. The PCA results displayed two clusters of CD-inflamed samples: one close to (Inflamed_1) and the other far away (Inflamed_2) from the non-inflamed samples. Inflamed_1 was rich in anti-TNF durable responders (DRs), and Inflamed_2 was enriched in non-durable responders (NDRs). The CiberSortx results showed that the cell fraction of activated fibroblasts was six times higher in Inflamed_2 than in Inflamed_1. Validation with public gene expression datasets (GSE16879) revealed that the activated fibroblasts were enriched in NDRs over Next, we used DRs by 1.9 times pre-treatment and 7.5 times after treatment. Fibroblast activation protein (FAP) was overexpressed in the Inflamed_2 and was also overexpressed in the NDRs in both the RISK and GSE16879 datasets. The activation of fibroblasts may play a role in resistance to anti-TNF therapy. Characterizing fibroblasts in inflamed tissues at diagnosis may help to identify patients who are likely to respond to anti-TNF therapy.
Files in This Item:
T202400783.pdf Download
DOI
10.3390/ijms241914799
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Chun, Jaeyoung(천재영) ORCID logo https://orcid.org/0000-0002-4212-0380
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198021
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links