Enrichment of Activated Fibroblasts as a Potential Biomarker for a Non-Durable Response to Anti-Tumor Necrosis Factor Therapy in Patients with Crohn's Diseaseopen access
- Authors
- Park, Soo-Kyung; Lee, Gi-Young; Kim, Sangsoo; Lee, Chil-Woo; Choi, Chang-Hwan; Kang, Sang-Bum; Kim, Tae-Oh; Chun, Jaeyoung; Cha, Jae-Myung; Im, Jong-Pil; Ahn, Kwang-Sung; Kim, Seon-Young; Kim, Min-Suk; Lee, Chang-Kyun; Park, Dong-Il
- Issue Date
- Oct-2023
- Publisher
- MDPI
- Keywords
- anti-tumor necrosis factor therapy; Crohn's disease; activated fibroblasts; RNA sequencing
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.24, no.19
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- Volume
- 24
- Number
- 19
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69248
- DOI
- 10.3390/ijms241914799
- ISSN
- 1661-6596
1422-0067
- 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
- There are no files associated with this item.
- Appears in
Collections - ETC > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69248)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.