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肺腺癌相关蛋白 6 作为过敏性肺炎的临床标志物:一项荟萃分析和生物信息学分析。

Krebs von den lungen-6 as a clinical marker for hypersensitivity pneumonitis: A meta-analysis and bioinformatics analysis.

机构信息

Clinical Medical College of Chengdu Medical College. Chengdu, Sichuan, China.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.

出版信息

Front Immunol. 2022 Nov 30;13:1041098. doi: 10.3389/fimmu.2022.1041098. eCollection 2022.

DOI:10.3389/fimmu.2022.1041098
PMID:36532009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9748086/
Abstract

AIM

Hypersensitivity pneumonitis (HP), also referred to as exogenous allergic alveolitis, is one of the most common interstitial lung diseases (ILDs). A potential immune biomarker, Krebs von den lgen-6 (KL-6) characterizes the progression and severity of HP. The meta-analysis in this study was conducted to elucidate the variations in the concentrations of KL-6 in different types of HP.

METHODS

A systematic search of various databases such as EMBASE, Pubmed, CNKI, VIP, Web of Science, and WanFang was carried out to find relevant published articles between January 1980 and August 2022 that explored the relationship between KL-6 and allergic pneumonia. Standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect sizes for comparison among different groups. The GSE47460 and GSE150910 datasets were downloaded to extract and validate the differences in KL-6 mRNA expression between HP lung tissue and healthy controls. Furthermore, the single-cell sequencing dataset GSE135893 was downloaded to extract KL-6 mRNA expression in type II alveolar epithelial cells to validate the differences between HP and healthy controls. Two researchers evaluated the quality of the included studies by employing Newcastle-Ottawa Scale. All the qualified studies were subjected to statistical analyses carried out utilizing RevMan 5.2, Stata 11.0, and R software 4.1.3.

RESULTS

Twenty studies aligned perfectly with the inclusion criteria of the meta. The concentrations of KL-6 were substantially higher in the blood of HP patients as compared to the control group. Subgroup analyses were carried out in accordance with the allergen source and the results revealed that patients with different allergens had higher blood KL-6 concentrations than healthy controls. Additionally, different subgroups of subjects were created for meta-analysis as per the fibrosis status, race, measurement method, and sample type. The concentration of KL-6 in blood was much higher in all HP subgroups than in healthy control groups. Moreover, the bioinformatics analysis revealed that KL-6 mRNA expression was higher in HP lung tissue and type II alveolar epithelial cells as compared to healthy controls.

CONCLUSION

The present meta-analysis and bioinformatics analysis suggested that the concentration levels of KL-6 varied between HP patients and healthy individuals, and the KL-6 concentrations may be higher in the blood samples of HP patients.

SYSTEMATIC REVIEW REGISTRATION

https://www.crd.york.ac.uk/prospero/, CRD42022355334.

摘要

目的

过敏性肺炎(HP),又称外源性过敏性肺泡炎,是最常见的间质性肺疾病(ILDs)之一。 一种潜在的免疫生物标志物,Krebs von den lgen-6(KL-6),可用于描述 HP 的进展和严重程度。本研究的荟萃分析旨在阐明不同类型 HP 中 KL-6 浓度的变化。

方法

通过系统检索 EMBASE、Pubmed、CNKI、VIP、Web of Science 和 WanFang 等数据库,检索 1980 年 1 月至 2022 年 8 月期间探讨 KL-6 与过敏性肺炎之间关系的相关文献。采用标准化均数差(SMD)和 95%置信区间(CI)作为不同组间比较的效应量。下载 GSE47460 和 GSE150910 数据集以提取和验证 HP 肺组织与健康对照组之间 KL-6mRNA 表达的差异。此外,下载单细胞测序数据集 GSE135893 以提取 HP 与健康对照组之间 II 型肺泡上皮细胞中 KL-6mRNA 表达的差异。两位研究者采用 Newcastle-Ottawa 量表评估纳入研究的质量。对所有符合条件的研究进行统计分析,采用 RevMan 5.2、Stata 11.0 和 R 软件 4.1.3。

结果

共有 20 项研究完全符合荟萃分析的纳入标准。HP 患者血液中 KL-6 的浓度明显高于对照组。根据过敏原来源进行亚组分析,结果显示不同过敏原的患者血液 KL-6 浓度高于健康对照组。此外,根据纤维化状态、种族、测量方法和样本类型创建了不同的亚组进行荟萃分析。所有 HP 亚组的血液 KL-6 浓度均明显高于健康对照组。此外,生物信息学分析表明,HP 肺组织和 II 型肺泡上皮细胞中的 KL-6mRNA 表达高于健康对照组。

结论

本荟萃分析和生物信息学分析表明,KL-6 在 HP 患者和健康个体之间的浓度水平不同,并且 HP 患者的血液样本中 KL-6 浓度可能更高。

系统评价注册

https://www.crd.york.ac.uk/prospero/,CRD42022355334。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3fd/9748086/a852a14f640e/fimmu-13-1041098-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3fd/9748086/a852a14f640e/fimmu-13-1041098-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3fd/9748086/a852a14f640e/fimmu-13-1041098-g007.jpg

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