{"title":"内皮素-1作为系统性硬化症的候选生物标志物：一项分级评估的系统评价和meta -回归分析","authors":"Arduino A Mangoni, Angelo Zinellu","doi":"10.1177/11772719251318555","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There is an ongoing search for novel biomarkers of vascular dysfunction, extent of fibrosis and organ involvement in systemic sclerosis (SSc).</p><p><strong>Objectives: </strong>We critically appraised the studies investigating the circulating concentrations of endothelin-1 in SSc patients and healthy controls.</p><p><strong>Design: </strong>This was a systematic review with meta-analysis.</p><p><strong>Data sources and methods: </strong>We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 15 June 2024. We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively.</p><p><strong>Results: </strong>Endothelin-1 concentrations were significantly higher in SSc patients than in controls (26 studies; standardised mean difference, SMD = 0.98, 95% CI 0.73-1.23, <i>P</i> < .001; moderate certainty of evidence). In SSc patients, there were no significant differences in endothelin-1 concentrations between those with limited and diffuse cutaneous SSc (10 studies; SMD = 0.32, 95% CI -0.07 to 0.71 <i>P</i> = .11; very low certainty), and with and without digital ulcers (5 studies; SMD = 0.82, 95% CI -0.06 to 1.69, <i>P</i> = .066; very low certainty), pulmonary arterial hypertension (7 studies; SMD = 0.22, 95% CI -0.01 to 0.45, <i>P</i> = .066; very low certainty) or interstitial lung disease (3 studies; SMD = 0.09, 95% CI -0.18 to 0.35, <i>P</i> = .51; very low certainty). There was limited evidence in SSc patients with different video capillaroscopy pattern and telangiectasias. Subgroup and meta-regression analyses showed significant associations between the effect size and geographical location (studies investigating SSc patients and controls), year of publication (studies investigating SSc patients with limited and diffuse cutaneous SSc), and biological matrix assessed (studies investigating SSc patients with and without digital ulcers).</p><p><strong>Conclusion: </strong>The results of this systematic review and meta-analysis highlight the potential role of endothelin-1 as a candidate biomarker of SSc. Further research is warranted to determine the utility of measuring endothelin-1 in SSc subgroups with different extent of fibrosis and organ involvement.</p><p><strong>Registration: </strong>PROSPERO registration number - CRD42024566461.</p>","PeriodicalId":47060,"journal":{"name":"Biomarker Insights","volume":"20 ","pages":"11772719251318555"},"PeriodicalIF":3.4000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11846126/pdf/","citationCount":"0","resultStr":"{\"title\":\"Endothelin-1 as a Candidate Biomarker of Systemic Sclerosis: A GRADE-Assessed Systematic Review and Meta-Analysis With Meta-Regression.\",\"authors\":\"Arduino A Mangoni, Angelo Zinellu\",\"doi\":\"10.1177/11772719251318555\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>There is an ongoing search for novel biomarkers of vascular dysfunction, extent of fibrosis and organ involvement in systemic sclerosis (SSc).</p><p><strong>Objectives: </strong>We critically appraised the studies investigating the circulating concentrations of endothelin-1 in SSc patients and healthy controls.</p><p><strong>Design: </strong>This was a systematic review with meta-analysis.</p><p><strong>Data sources and methods: </strong>We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 15 June 2024. We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively.</p><p><strong>Results: </strong>Endothelin-1 concentrations were significantly higher in SSc patients than in controls (26 studies; standardised mean difference, SMD = 0.98, 95% CI 0.73-1.23, <i>P</i> < .001; moderate certainty of evidence). In SSc patients, there were no significant differences in endothelin-1 concentrations between those with limited and diffuse cutaneous SSc (10 studies; SMD = 0.32, 95% CI -0.07 to 0.71 <i>P</i> = .11; very low certainty), and with and without digital ulcers (5 studies; SMD = 0.82, 95% CI -0.06 to 1.69, <i>P</i> = .066; very low certainty), pulmonary arterial hypertension (7 studies; SMD = 0.22, 95% CI -0.01 to 0.45, <i>P</i> = .066; very low certainty) or interstitial lung disease (3 studies; SMD = 0.09, 95% CI -0.18 to 0.35, <i>P</i> = .51; very low certainty). There was limited evidence in SSc patients with different video capillaroscopy pattern and telangiectasias. Subgroup and meta-regression analyses showed significant associations between the effect size and geographical location (studies investigating SSc patients and controls), year of publication (studies investigating SSc patients with limited and diffuse cutaneous SSc), and biological matrix assessed (studies investigating SSc patients with and without digital ulcers).</p><p><strong>Conclusion: </strong>The results of this systematic review and meta-analysis highlight the potential role of endothelin-1 as a candidate biomarker of SSc. 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引用次数: 0
摘要
背景：目前正在寻找系统性硬化症（SSc）中血管功能障碍、纤维化程度和器官累及的新生物标志物。目的：我们对研究SSc患者和健康对照者循环内皮素-1浓度的研究进行了批判性评价。设计：这是一项采用meta分析的系统综述。数据来源和方法：我们检索了从成立到2024年6月15日的电子数据库（PubMed， Scopus和Web of Science）。我们分别使用JBI关键评估清单和GRADE评估偏倚风险和证据确定性。结果：SSc患者的内皮素-1浓度显著高于对照组(26项研究；标准化均差，SMD = 0.98, 95% CI 0.73 ~ 1.23, P = 0.11；非常低的确定性)，以及有无数字溃疡(5项研究；SMD = 0.82, 95% CI -0.06 ~ 1.69, P = 0.066；非常低的确定性)，肺动脉高压(7项研究；SMD = 0.22, 95% CI -0.01 ~ 0.45, P = 0.066；非常低的确定性)或间质性肺病(3项研究；SMD = 0.09, 95% CI -0.18 ~ 0.35, P = 0.51；非常低的确定性)。在不同视频毛细血管镜模式和毛细血管扩张的SSc患者中，证据有限。亚组和荟萃回归分析显示，效应大小与地理位置（调查SSc患者和对照组的研究）、发表年份（调查局限性和弥漫性皮肤SSc患者的研究）和评估的生物基质（调查伴有和不伴有数字溃疡的SSc患者的研究）之间存在显著关联。结论：本系统综述和荟萃分析的结果突出了内皮素-1作为SSc候选生物标志物的潜在作用。需要进一步的研究来确定内皮素-1在不同程度纤维化和器官受累的SSc亚组中的效用。报名：普洛斯彼罗注册号- CRD42024566461。
Endothelin-1 as a Candidate Biomarker of Systemic Sclerosis: A GRADE-Assessed Systematic Review and Meta-Analysis With Meta-Regression.
Background: There is an ongoing search for novel biomarkers of vascular dysfunction, extent of fibrosis and organ involvement in systemic sclerosis (SSc).
Objectives: We critically appraised the studies investigating the circulating concentrations of endothelin-1 in SSc patients and healthy controls.
Design: This was a systematic review with meta-analysis.
Data sources and methods: We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 15 June 2024. We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively.
Results: Endothelin-1 concentrations were significantly higher in SSc patients than in controls (26 studies; standardised mean difference, SMD = 0.98, 95% CI 0.73-1.23, P < .001; moderate certainty of evidence). In SSc patients, there were no significant differences in endothelin-1 concentrations between those with limited and diffuse cutaneous SSc (10 studies; SMD = 0.32, 95% CI -0.07 to 0.71 P = .11; very low certainty), and with and without digital ulcers (5 studies; SMD = 0.82, 95% CI -0.06 to 1.69, P = .066; very low certainty), pulmonary arterial hypertension (7 studies; SMD = 0.22, 95% CI -0.01 to 0.45, P = .066; very low certainty) or interstitial lung disease (3 studies; SMD = 0.09, 95% CI -0.18 to 0.35, P = .51; very low certainty). There was limited evidence in SSc patients with different video capillaroscopy pattern and telangiectasias. Subgroup and meta-regression analyses showed significant associations between the effect size and geographical location (studies investigating SSc patients and controls), year of publication (studies investigating SSc patients with limited and diffuse cutaneous SSc), and biological matrix assessed (studies investigating SSc patients with and without digital ulcers).
Conclusion: The results of this systematic review and meta-analysis highlight the potential role of endothelin-1 as a candidate biomarker of SSc. Further research is warranted to determine the utility of measuring endothelin-1 in SSc subgroups with different extent of fibrosis and organ involvement.
Registration: PROSPERO registration number - CRD42024566461.
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