TY - JOUR
T1 - Endostatin as a biomarker of systemic sclerosis
T2 - insights from a systematic review and meta-analysis
AU - Mangoni, Arduino A.
AU - Zinellu, Angelo
PY - 2024/12/23
Y1 - 2024/12/23
N2 - Introduction: The critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating a such candidate biomarker, endostatin, an endogenous glycoprotein exerting anti-angiogenic effects, in SSc patients and healthy controls. Methods: A literature search was conducted in the electronic databases Web of Science, PubMed, and Scopus from inception to 27 May 2024. Risk of bias and certainty of evidence were assessed using the JBI checklist for analytical studies and GRADE, respectively. Results: In 19 eligible studies, circulating endostatin concentrations were significantly higher in SSc patients than controls (standard mean difference, SMD=0.90, 95% CI 0.56 to 1.23, p<0.001; low certainty of evidence). Endostatin concentrations were also significantly higher in SSc patients with digital ulcers than those without (SMD=0.43, 95% CI 0.24 to 0.62, p<0.001; very low certainty of evidence) and in patients with pulmonary arterial hypertension than those without (SMD=1.21, 95% CI 0.67 to 1.76, p<0.001; very low certainty of evidence). By contrast, no significant differences were observed between SSc patients with limited vs. diffuse disease and those with different video capillaroscopy patterns. There was limited evidence regarding endostatin concentrations in SSc patients with interstitial lung disease, telangiectasias, and gastrointestinal manifestations. There were no significant associations in meta-regression and subgroup analysis of studies investigating endostatin in SSc patients and controls between the effect size and various patient and study characteristics. Discussion: Therefore, the results of this systematic review and meta-analysis suggest that measuring endostatin can be useful in assessing the presence of SSc and specific complications, i.e., digital ulcers and pulmonary arterial hypertension, in these patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024558174.
AB - Introduction: The critical role played by vascular dysfunction and ineffective angiogenesis in the pathophysiology of systemic sclerosis (SSc) suggests that circulating biomarkers reflecting these alterations may be useful in the clinical evaluation of this patient group. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating a such candidate biomarker, endostatin, an endogenous glycoprotein exerting anti-angiogenic effects, in SSc patients and healthy controls. Methods: A literature search was conducted in the electronic databases Web of Science, PubMed, and Scopus from inception to 27 May 2024. Risk of bias and certainty of evidence were assessed using the JBI checklist for analytical studies and GRADE, respectively. Results: In 19 eligible studies, circulating endostatin concentrations were significantly higher in SSc patients than controls (standard mean difference, SMD=0.90, 95% CI 0.56 to 1.23, p<0.001; low certainty of evidence). Endostatin concentrations were also significantly higher in SSc patients with digital ulcers than those without (SMD=0.43, 95% CI 0.24 to 0.62, p<0.001; very low certainty of evidence) and in patients with pulmonary arterial hypertension than those without (SMD=1.21, 95% CI 0.67 to 1.76, p<0.001; very low certainty of evidence). By contrast, no significant differences were observed between SSc patients with limited vs. diffuse disease and those with different video capillaroscopy patterns. There was limited evidence regarding endostatin concentrations in SSc patients with interstitial lung disease, telangiectasias, and gastrointestinal manifestations. There were no significant associations in meta-regression and subgroup analysis of studies investigating endostatin in SSc patients and controls between the effect size and various patient and study characteristics. Discussion: Therefore, the results of this systematic review and meta-analysis suggest that measuring endostatin can be useful in assessing the presence of SSc and specific complications, i.e., digital ulcers and pulmonary arterial hypertension, in these patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024558174.
KW - biomarkers
KW - complications
KW - endostatin
KW - fibrosis
KW - ineffective angiogenesis
KW - systemic sclerosis
KW - vascular dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85214368916&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2024.1450176
DO - 10.3389/fimmu.2024.1450176
M3 - Review article
AN - SCOPUS:85214368916
SN - 1664-3224
VL - 15
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1450176
ER -