Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

Nakatani, Naoki; Masuo, Masahiro; Nukui, Yoshihisa; Tateishi, Tomoya; Kishino, Mitsuhiro; Tateishi, Ukihide; Morota, Kaori; Ohbo, Kazuyuki; Miyazaki, Yasunari

doi:10.1016/j.resinv.2020.08.002

Cited by 18 publications

(15 citation statements)

References 38 publications

(31 reference statements)

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“…Further, we found that high levels of HE4 were independently associated with the presence of RA-ILD in a multivariate logistic regression analysis. Consistent with our results, Nishiyama et al also showed that HE4 was a new biomarker to predict the prognosis of progressive fibrosing ILD (20). Taken together, these findings support a role of HE4 in risk stratification of ILD.…”

Section: Discussionsupporting

confidence: 92%

Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis

Liu

Chen

et al. 2021

Front. Med.

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Objective: Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA).Methods: This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer.Results: The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080, p < 0.001).Conclusion: Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).

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Section: Discussionsupporting

confidence: 92%

Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis

Liu

Chen

et al. 2021

Front. Med.

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“…Very recently, Zhang et al reported that serum HE4 levels were significantly increased in patients with systemic sclerosis (SSc)-ILD compared to SSc-non-ILD, which was consistent with our findings (19). Nishiyama et al also showed that HE4 was a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease (20). These findings were consistent with ours showing that HE4 was significantly associated with pulmonary involvements and renal involvements in patients with pSS.…”

Section: Discussionsupporting

confidence: 89%

Elevated Serum Human Epididymis Protein 4 Is Associated With Disease Activity and Systemic Involvements in Primary Sjögren’s Syndrome

et al. 2021

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BackgroundWe aimed to investigate the clinical utility of human epididymis protein 4, a tumor biomarker being widely utilized in clinical practice in the diagnosis of ovarian cancer, in primary Sjögren’s Syndrome (pSS).MethodsA total of 109 pSS patients and 113 healthy controls (HCs) were included in the study. HE4 were determined by Roche Cobas E601 electrochemical luminescence analyzer. Clinical and laboratory findings were reviewed, and the relationships between HE4 and clinical parameters were determined by Spearman’s correlation test. The European league against rheumatism Sjögren’s syndrome disease activity index (ESSDAI) was utilized to evaluate disease activity.FindingsThe levels of HE4 were significantly elevated in patients with pSS compared to HCs (103.65 pmol/L vs. 46.52 pmol/L, p<0.001). The levels of HE4 were positively correlated with ESSDAI scores (r=0.462, p<0.001). Significant positive correlations between the levels of HE4 with pulmonary involvements (r=0.442, p<0.001) and renal involvements (r=0.320, p=0.001) were observed. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.90 pmol/L and 128.05 pmol/L for distinguishing patients with pulmonary and renal involvements, with the areas under the ROC curve (AUCs) of 0.778 (95%CI 0.685-0.870, p<0.001) and 0.768 (95%CI 0.646-0.891, p=0.001), respectively. Among patients with pulmonary involvement, the levels of HE4 were positively correlated with the semiquantitative HRCT grade (r=0.417, p=0.016), and negatively correlated with the percentage of forced vital capacity (FVC) (r= -0.460, p=0.047) and diffusing capacity of the lung for carbon monoxide (DLco) (r= -0.623, p=0.004). For patients with renal involvement, HE4 was positively correlated with creatinine (r=0.588, p=0.021) and negatively correlated with estimated glomerular filtration rate (r= -0.599, p=0.030).ConclusionsOur findings demonstrated a novel role of HE4 in clinical stratification of pSS, suggesting that introducing HE4 to the current pSS test panel may provide additional diagnostic value, particularly in evaluating disease activity and pulmonary/renal involvements.

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“…Previous studies have shown that serum HE4 could serve as a biomarker for predicting death and prognosis in ovarian cancer, chronic heart failure patients and progressive fibrosing interstitial lung diseases. 13,16,35 Taken together, we believe that serum HE4 is a biomarker of ARDS induced by sepsis and is associated with the prognosis of sepsis.…”

Section: Discussionmentioning

confidence: 78%

“…14,18 Indeed, elevated serum HE4 concentrations were reported in a series of studies to be associated with pulmonary fibrosis, and presumably a potential biomarker for the evaluation of the diagnosis, severity and progression of pulmonary fibrosis. 17,[19][20][21] However, the concentrations of serum HE4 in ARDS patients have not yet been explored. In this study, we tested the serum HE4 levels of patients with ARDS and investigated its clinical value for the diagnosis and prognosis of ARDS.…”

Section: Introductionmentioning

confidence: 99%

Serum human epididymis secretory protein 4 correlates with sepsis-associated acute respiratory distress syndrome and 28-day mortality in critically ill patients

et al. 2022

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Background: Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. Methods: One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman’s correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. Results: Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all P<0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cutoff value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5 pmol/L. Conclusions: The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

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Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

Cited by 18 publications

References 38 publications

Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis

Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis

Elevated Serum Human Epididymis Protein 4 Is Associated With Disease Activity and Systemic Involvements in Primary Sjögren’s Syndrome

Serum human epididymis secretory protein 4 correlates with sepsis-associated acute respiratory distress syndrome and 28-day mortality in critically ill patients

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