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
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
International journal of molecular sciences - 24(2023), 19 vom: 30. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Park, Soo-Kyung [VerfasserIn] |
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| Links: |
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| Themen: |
63231-63-0 |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 23.10.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms241914799 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363272100 |
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| 100 | 1 | |a Park, Soo-Kyung |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Crohn’s disease | |
| 650 | 4 | |a RNA sequencing | |
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| 650 | 4 | |a anti-tumor necrosis factor therapy | |
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| 700 | 1 | |a Lee, Gi-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Sangsoo |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chil-Woo |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Chang-Hwan |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Sang-Bum |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Tae-Oh |e verfasserin |4 aut | |
| 700 | 1 | |a Chun, Jaeyoung |e verfasserin |4 aut | |
| 700 | 1 | |a Cha, Jae-Myung |e verfasserin |4 aut | |
| 700 | 1 | |a Im, Jong-Pil |e verfasserin |4 aut | |
| 700 | 1 | |a Ahn, Kwang-Sung |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Seon-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Min-Suk |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Chang-Kyun |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Dong-Il |e verfasserin |4 aut | |
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