Clinical Significance of Cold-Inducible RNA-Binding Protein in Idiopathic Pulmonary Fibrosis
Clinical Significance of Cold-Inducible RNA-Binding Protein in Idiopathic Pulmonary Fibrosis
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DOI：
10.1016/j.chest.2021.06.067
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发表时间：
2021-12-03
期刊：
影响因子：
9.6
通讯作者：
Suda, Takafumi
中科院分区：
文献类型：
--
作者：
Hozumi, Hironao;Kataoka, Kensuke;Suda, Takafumi
背景：特发性肺纤维化（IPF）与预后不良相关，临床病程多变。早期识别疾病进展和死亡高风险患者将导致早期治疗干预，从而改善结局。冷诱导RNA结合蛋白（CIRBP）是细胞应激反应的产物，与多种生物学过程有关，包括细胞存活和增殖。研究问题：CIRBP是预测IPF患者预后的有用生物标志物吗？研究设计和方法：本研究纳入了来自两家独立医院的95例和93例IPF患者（分别为推导队列和验证队列）。回顾性分析了IPF诊断时血清CIRBP水平与诊断后1年内疾病进展（即预测FVC或死亡百分比相对下降>= 10%）和全因死亡率的相关性。判别性能预测这些结果进行了评估，使用c-index.RESULTS：血清和肺组织CIRBP水平较高的IPF患者比对照组。在推导队列中，CIRBPlow亚组的1年疾病进展率显著高于CIRBPlow亚组，累积生存率显著低于CIRBPlow亚组，验证队列中重复了该结果。在多变量分析中，高血清CIRBP水平与两个队列中较高的1年疾病进展率和全因死亡率独立相关。性别-年龄-生理学（GAP）和血清CIRBP模型相结合，改善了预测1年疾病进展和全因死亡率的c指数。在GAP I期患者中，血清CIRBP的c指数特别高。解释：本研究成功验证了血清CIRBP水平是IPF 1年疾病进展和全因死亡率的独立预测因子。CIRBP是一种很有前途的生物标志物，可以帮助识别高风险IPF患者，尤其是在早期阶段。
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis with variable clinical course. Early identification of patients at high risk for disease progression and death would lead to early therapeutic intervention and thereby improvement of outcomes. Cold-inducible RNA-binding protein (CIRBP) is produced in response to cellular stresses, which is implicated in multiple biological processes, including cell survival and proliferation.RESEARCH QUESTION: Is CIRBP a useful biomarker for predicting the outcomes of patients with IPF? STUDY DESIGN AND METHODS: This study included 95 and 93 patients with IPF from two independent hospitals (derivation and validation cohorts, respectively). The associations of serum CIRBP level on IPF diagnosis with disease progression within 1 year after diagnosis (ie, >= 10% relative decline in percent predicted FVC or death) and all-cause mortality were retrospectively analyzed. Discrimination performances for predicting these outcomes were evaluated using the c-index.RESULTS: Serum and lung tissue CIRBP levels were higher in patients with IPF than in control subjects. In the derivation cohort, the CIRBPhigh subgroup had significantly higher 1-year disease progression rates and lower cumulative survival rates than the CIRBPlow sub-group, and the results were replicated in the validation cohort. In multivariate analyses, high serum CIRBP level was independently associated with higher 1-year disease progression and all-cause mortality rates in both cohorts. Combining the Gender-Age-Physiology (GAP) and serum CIRBP models improved the c-indexes for predicting 1-year disease progression and all-cause mortality compared with that of each model alone. The c-indexes of serum CIRBP were particularly high in patients with GAP stage I.INTERPRETATION: This study successfully validated that serum CIRBP level was an independent predictor of 1-year disease progression and all-cause mortality in IPF. CIRBP is a promising biomarker that can help identify high-risk patients with IPF, especially in the early stage.