특발성 폐섬유증 환자 유래 섬유아세포의 콜라겐 유전자 발현양상과 임상 예후 연관성 분석 = Collagen Genes Expression Profiles in IPF fibroblast and Their Prognostic Implications

다국어 초록 (Multilingual Abstract)

Background: Idiopathic Pulmonary Fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant extracellular matrix remodeling. While type I and III collagens are known contributors, the extensive transcriptional landscape and prognostic significance of diverse collagen genes in IPF fibroblasts remain unclear.
Methods: RNA sequencing was conducted on primary lung fibroblasts from 33 IPF patients and 10 non-fibrotic controls. Differential expression of collagen genes was analyzed using EdgeR’s exact test, with significance defined as false discovery rate-adjusted p < 0.05. Prognostic significance was assessed using Cox regression and Kaplan–Meier survival analysis.
Results: Among 6,920 differentially expressed genes, 17 were collagen genes, of which 14 — including COL1A1, COL1A2, COL3A1, COL4A4, COL4A5, COL4A6, COL5A2, COL6A6, COL8A1, COL11A1, COL14A1, COL18A1, COL24A1, and COL27A1 — were markedly upregulated in IPF fibroblasts, whereas COL5A3, COL13A1, and COL16A1 were downregulated. Seven genes - COL3A1, COL4A4, COL5A2, COL6A6, COL14A1, COL24A1 and COL27A1 - were associated with reduced survival in univariate Cox regression and/or Kaplan–Meier analyses. Among these, COL4A4 was as an independent predictor of mortality in multivariate models.
Conclusion: COL4A4 was identified as a novel collagen gene with prognostic relevance in IPF, functioning as an independent predictor of mortality. These findings indicate that their distinct transcriptional upregulation in IPF fibroblasts may contribute to adverse clinical outcomes and suggest that fibroblast-derived collagen expression signatures hold potential as prognostic markers and therapeutic targets.

목차 (Table of Contents)

• Contents i
• Contents of Tables iii
• Contents of Figures iv
• Abstract v
• Ⅰ. Introduction 1
• Ⅱ. Materials and Methods 3
• A. Study subjects 3
• B. Fibroblast culture 3
• C. DAB staining of cultured fibroblasts 4
• D. Total RNA sequencing data processing 4
• E. Differential expression analysis 5
• F. Statistical analysis 5
• Ⅲ. Results 7
• A. Patient characteristics 7
• B. Differential expression of collagen genes in human lung derived fibroblasts 7
• C. Survival analysis based on collagen gene expression in IPF patients 8
• Ⅳ. Discussion 9
• V. References 15
• VI. Tables and Figures 18
• 국문 요약 29
• 감사의 글 31