Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, Republic of Korea.
Int J Mol Sci. 2024 Jan 2;25(1):599. doi: 10.3390/ijms25010599.
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, , , , , , , , and were up-regulated, and was down-regulated in the samples of advanced IPF. Only CTSB showed significant differences in expression based on Western blotting ( = 12; < 0.001) and immunohistochemistry between the three groups of the independent IPF cohort. In the retrospective validation cohort ( = 78), serum CTSB levels were higher in the progressive group ( = 25) than in the control ( = 29, mean 7.37 ng/mL vs. 2.70 ng/mL, < 0.001) and nonprogressive groups ( = 24, mean 7.37 ng/mL vs. 2.56 ng/mL, < 0.001). In the prospective validation cohort ( = 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, < 0.001). After adjusting for baseline FVC, we found that CTSB was independently associated with IPF progression (adjusted OR = 2.61, < 0.001). Serum CTSB levels significantly predicted IPF progression (AUC = 0.944, < 0.001). Serum CTSB level significantly distinguished the progression of IPF from the non-progression of IPF or healthy control.
特发性肺纤维化 (IPF) 的进展是多样且不可预测的。我们确定并验证了一个新的 IPF 进展生物标志物。为了确定预测进展的候选基因，我们评估了三个肺样本队列中晚期 IPF 患者与早期 IPF 患者和对照者的差异表达基因。使用独立的 IPF 临床队列的肺组织样本的免疫组织化学和 Western blot 验证候选基因表达。使用回顾性验证队列的血清样本的酶联免疫吸附试验评估生物标志物潜力。我们验证了最终的候选基因在前瞻性验证队列中反映了 IPF 的进展。在肺组织的 RNA-seq 比较分析中， 、 、 、 、 、 和 上调， 下调。仅 CTSB 在独立 IPF 队列的三组之间的 Western blot（ = 12； < 0.001）和免疫组织化学中显示出显著差异。在回顾性验证队列（ = 78）中，进展组的血清 CTSB 水平（ = 25）高于对照组（ = 29，平均 7.37ng/mL 比 2.70ng/mL， < 0.001）和非进展组（ = 24，平均 7.37ng/mL 比 2.56ng/mL， < 0.001）。在前瞻性验证队列（ = 129）中，进展组的血清 CTSB 水平高于非进展组（平均 8.30ng/mL 比 3.00ng/mL， < 0.001）。在调整了基线 FVC 后，我们发现 CTSB 与 IPF 进展独立相关（调整后的 OR = 2.61， < 0.001）。血清 CTSB 水平显著预测 IPF 进展（AUC = 0.944， < 0.001）。血清 CTSB 水平显著区分了 IPF 的进展与非进展或健康对照。
Zotero 插件
