Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis
The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
International journal of molecular sciences - 25(2024), 1 vom: 02. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yeo, Hye Ju [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 12.01.2024 Date Revised 13.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms25010599 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36694357X |
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| 100 | 1 | |a Yeo, Hye Ju |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Development of a Novel Biomarker for the Progression of Idiopathic Pulmonary Fibrosis |
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| 500 | |a Date Revised 13.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The progression of idiopathic pulmonary fibrosis (IPF) is diverse and unpredictable. We identified and validated a new biomarker for IPF progression. To identify a candidate gene to predict progression, we assessed differentially expressed genes in patients with advanced IPF compared with early IPF and controls in three lung sample cohorts. Candidate gene expression was confirmed using immunohistochemistry and Western blotting of lung tissue samples from an independent IPF clinical cohort. Biomarker potential was assessed using an enzyme-linked immunosorbent assay of serum samples from the retrospective validation cohort. We verified that the final candidate gene reflected the progression of IPF in a prospective validation cohort. In the RNA-seq comparative analysis of lung tissues, CD276, COL7A1, CTSB, GLI2, PIK3R2, PRAF2, IGF2BP3, and NUPR1 were up-regulated, and ADAMTS8 was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting (n = 12; p < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort (n = 78), serum CTSB levels were higher in the progressive group (n = 25) than in the control (n = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, p < 0.001) and nonprogressive groups (n = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, p < 0.001). In the prospective validation cohort (n = 129), serum CTSB levels were higher in the progressive group than in the nonprogressive group (mean 8.30 ng/mL vs. 3.00 ng/mL, p < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, p < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, p < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a IPF | |
| 650 | 4 | |a cathepsin | |
| 650 | 4 | |a prediction | |
| 650 | 4 | |a prognosis | |
| 650 | 4 | |a progression | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a ADAMTS8 protein, human |2 NLM | |
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| 650 | 7 | |a ADAMTS Proteins |2 NLM | |
| 650 | 7 | |a EC 3.4.24.- |2 NLM | |
| 650 | 7 | |a CD276 protein, human |2 NLM | |
| 650 | 7 | |a B7 Antigens |2 NLM | |
| 650 | 7 | |a PRAF2 protein, human |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a COL7A1 protein, human |2 NLM | |
| 650 | 7 | |a Collagen Type VII |2 NLM | |
| 700 | 1 | |a Ha, Mihyang |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Dong Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Hye Rin |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yun Hak |e verfasserin |4 aut | |
| 700 | 1 | |a Cho, Woo Hyun |e verfasserin |4 aut | |
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