Serum Human Epididymis Protein Research Articles

Increased serum human epididymis protein 4 is associated with disease activity and systemic involvement in pediatric-onset systemic lupus erythematosus.

We aimed to investigate human epididymis protein 4 (HE4) as a potential biomarker in patients with pediatric-onset systemic lupus erythematosus (pSLE), particularly on the association of serum HE4 levels with disease activity and other laboratory tests. We included 137 patients with pSLE and 75 age- and sex-matched healthy controls (HCs). Serum HE4 level was measured by a chemiluminescent microparticle on an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Comparisons between groups were performed using the independent Student t-test, Mann-Whitney U test, Chi-square test, or Fisher's exact test, as appropriate. We also determined the relationships between HE4 and clinical parameters and evaluated disease activity using SLE Disease Activity Index (SLEDAI) and renal SLEDAI (rSLEDAI). Serum HE4 levels in patients with pSLE (44.6 pmol/L; IQR, 32.5-73.5) were significantly higher than those in HCs (38.9 pmol/L; IQR, 34-46.1). HE4 levels were significantly higher in moderate to severe disease activities (57.4 pmol/L, IQR 37.7-164.5) than in mild disease activities (38.8 pmol/L, IQR 30.1-48.5) or HCs (38.9 pmol/L, IQR 34.0-46.1), as well as in active renal disease activities (77.2 pmol/L, IQR 47.4-224.1) than in inactive renal disease activities (36.1 pmol/L, IQR 27.8-46.7). The ROC curve analysis showed that HE4 could discriminate pSLE with renal (AUC, 0.717; 95% CI, 0.632-0.801), hematological (AUC, 0.740; 95% CI, 0.648-0.831), and cardiovascular involvement (AUC:0.775, 95% CI 0.669-0.880). Serum HE4 levels significantly correlated with several indicators related to renal morbidity, such as creatinine, blood urea nitrogen, uric acid, cystatin C, urine protein/24 h, etc. Serum HE4 levels in pSLE were elevated and highly associated with disease activity and systemic involvement, indicating HE4 as a potential biomarker for pSLE.

P-314 Is there a relationship between adenomyosis ultrasonographic findings and serum Human epididymis protein 4 (HE4) ?

Abstract Abstract withdrawn by the authors

Evaluating the effectiveness of pre-operative diagnosis of ovarian cancer using minimally invasive liquid biopsies by combining serum human epididymis protein 4 and cell-free DNA in patients with an ovarian mass

ObjectiveTo assess the feasibility of scalable, objective, and minimally invasive liquid biopsy-derived biomarkers such as cell-free DNA copy number profiles, human epididymis protein 4 (HE4), and cancer antigen 125 (CA125)...

Use of Sensor Array Analysis to Detect Ovarian Cancer through Breath, Urine, and Blood: A Case-Control Study.

Ovarian cancer (OC) is the eighth most common cancer in women. Since screening programs do not exist, it is often diagnosed in advanced stages. Today, the detection of OC is based on clinical examination, transvaginal ultrasound (US), and serum biomarker (Carbohydrate Antigen 125 (CA 125) and Human Epididymis Protein 4 (HE4)) dosage, with a sensitivity of 88% and 95%, respectively, and a specificity of 84% for US and 76% for biomarkers. These methods are clearly not enough, and OC in its early stages is often missed. Many scientists have recently focused their attention on volatile organic compounds (VOCs). These are gaseous molecules, found in the breath, that could provide interesting information on several diseases, including solid tumors. To detect VOCs, an electronic nose was invented by a group of researchers. A similar device, the e-tongue, was later created to detect specific molecules in liquids. For the first time in the literature, we investigated the potential use of the electronic nose and the electronic tongue to detect ovarian cancer not just from breath but also from urine, blood, and plasma samples.

Elevated level of serum human epididymis protein 4 (HE4) predicts disease severity and mortality in COVID-19 pneumonia

BackgroundWe retrospectively analyzed serum level of human epididymis protein 4 (HE4) as a pulmonary inflammatory biomarker in patients with COVID-19 pneumonia in association with disease severity and outcome.MethodsNinety-nine (40 critically ill, 40 severe and 19 mild) COVID-19 patients and as controls 25 age- and sex-matched non-COVID-19 bacterial sepsis subjects were included. Serum HE4 was measured by an immunoassay (Architect® i1000SR, Abbott) in the baseline samples of all study participants obtained at intensive care unit (ICU) admission or during outpatient clinic visit and follow-up sera were available in case of 30 COVID-19 subjects with life-threating conditions. Associations were studied between serum HE4, routinely available laboratory parameters, clinical characteristics, and disease progression.ResultsBaseline HE4 level was significantly higher (P < 0.0001) in critically ill (524.7 [300.1–1153.0] pmol/L) than severe COVID-19 subjects (157.4 [85.2-336.9] pmol/L) and in mild SARS-CoV-2 infection (46.7 [39.1–57.2] pmol/L). Similarly increased HE4 concentrations were found in bacterial sepsis (1118.0 [418.3–1953.0] pmol/L, P = 0.056) compared to critically ill COVID-19 individuals. Serum HE4 levels significantly correlated with age, SOFA-score, inflammation-dependent biomarkers, and the degree of lung manifestation evaluated by chest CT examination in ICU COVID-19 individuals. Based on ROC-AUC curve analysis, baseline HE4 independently indicated the severity of COVID-19 with an AUC value of 0.816 (95% CI [0.723–0.908]; P < 0.0001), while binary logistic regression test found HE4 as an independent prognostic parameter for death (OR: 10.618 [2.331–48.354]; P = 0.002). Furthermore, COVID-19 non-survivors showed much higher baseline HE4 levels without a substantial change under treatment vs. survivors (P < 0.0001). Finally, pre-treatment HE4 level of ≥ 331.7 pmol/L effectively predicted a larger risk for mortality (Log-Rank P < 0.0001) due to severe COVID-19 pneumonia.ConclusionElevated serum HE4 level at ICU admission highly correlates with COVID-19 severity and predicts disease outcome.

Serum human epididymis protein 4 is associated with disease severity in patients with IgA nephropathy

BackgroundHuman epididymis protein 4 (HE4) is a promising tumor biomarker primarily utilized for the detection of ovarian cancer. However, its potential as a novel diagnostic indicator for immunoglobulin A nephropathy (IgAN) remains unknown. The objective of this study was to investigate the feasibility of serum HE4 as a novel biomarker for patients with IgAN. MethodsThis study enrolled a total of 89 hospitalized patients with IgAN at Peking University Shenzhen Hospital between July 2020 and December 2022, along with 60 healthy control subjects matched for sex and age without evidence of comorbidities. Serum HE4 levels were measured using the Abbott Alinity automated immune analyzer, and the correlation between serum HE4 levels and biochemical markers of renal damage as well as clinicopathologic features in IgAN patients were analyzed. ResultsIn this study, serum HE4 levels were significantly elevated in patients with IgAN compared to healthy controls (116.43 ± 103.61 pmol/L vs. 35.57 ± 9.33 pmol/L, p < 0.001). There was a positive correlation between serum HE4 levels and blood urea nitrogen (r = 0.58, p < 0.001), creatinine (r = 0.73, p < 0.001), cystatin C (r = 0.82, p < 0.001), β2-microglobulin (r = 0.77, p < 0.001), α1-microglobulin (r = 0.75, p < 0.001), and glomerulosclerosis ratio (r = 0.56, p < 0.001). Conversely, a negative correlation was observed between serum HE4 levels and hemoglobin (r = -0.42, p < 0.001), albumin (r = -0.44, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = -0.83, p < 0.001). In HE4+ IgAN patients, a higher glomerulosclerosis ratio (p < 0.01) and lower eGFR levels (p < 0.001) were observed compared to HE4- patients. Furthermore, patients with higher pathological classification grade also had higher serum HE4 levels. ConclusionsSerum HE4 levels were significantly associated with both renal function and the pathological classification of patients with IgAN, indicating that HE4 may serve as a promising biomarker for assessing the severity of IgAN.

Elevation of serum human epididymis protein 4 (HE4) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as predicting factors for the occurrence of acute kidney injury on chronic kidney disease: a single-center retrospective self-control study.

Objectives: To evaluate whether novel biomarkers of renal injury, serum HE4 and NT-proBNP could predict acute kidney injury (AKI) on chronic kidney disease (CKD) (A on C) and assess the specificity and efficiency of serum creatinine (SCr), HE4 and NT-proBNP in identifying potential AKI. Meanwhile, the potential early-warning value of HE4 and NT-proBNP in CKD patients was explored. Methods: We performed a single-center, retrospective cohort study of 187 adult CKD patients. 32 AKI (grades 1-2) patients with pre-existing CKD (stages 3-5) were Group 1, 59 patients of CKD (stages 4-5) were Group 2. Another 96 patients of CKD (stages 1-3) were Group 3. All patients received general treatments, Group 1 patients received Chinese herb formulation (Chuan Huang Fang-Ⅱ, CHF-Ⅱ) simultaneously. These 155 CKD (stages 1-5) without AKI patients were observed for descriptive analysis. Results: HE4 in Group 1 (860.63 ± 385.40) was higher than that in Group 2 (673.86 ± 283.58) before treatments. BUN, SCr, UA, NGAL, IL18, HE4 and NT-proBNP in Group 1 were lower, while eGFR was higher (p < 0.01, after vs. before treatments). In Group 1, both HE4 and NT-proBNP were positively correlated with SCr (respectively r = 0.549, 0.464) before treatments. The diagnostic performance of serum HE4 and NT-proBNP for A on C was 351.5pmol/L, 274.5pg/mL as the optimal cutoff value Area Under Curve (AUC) 0.860 (95% CI: 0.808 - 0.913, p < 0.001), [AUC 0.775 (95% CI: 0.697 - 0.853, p < 0.001), with a sensitivity and specificity of 100% and 66.5%, 87.5% and 48.8%, respectively]. In Group 2, serum HE4 was correlated with SCr (r = 0.682, p < 0.01) before treatments. Serum HE4 and NT-proBNP were elevated in advanced CKD stages, and were increased as CKD stages progressed with statistical significance. Conclusion: This work indicated serum HE4 and NT-proBNP should elevate in A on C and CKD patients, HE4 is positively correlated with the disease severity, and patients with higher HE4 and NT-proBNP usually have poorer prognosis. Thus, serum HE4 and NT-proBNP are impactful predictors of A on C. Additionally, serum HE4 and NT-proBNP have the potential to evaluate clinical efficacy of A on C.

Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis.

To systematically analyze the value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial cancer, so as to provide evidence-based medical evidence for the selection of serum tumor markers in the early screening of endometrial cancer. We comprehensively searched relevant literature in the Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, VIP, WanFang, and CBM from the date of establishment to November 31, 2021. Quality assessment of diagnostic accuracy studies 2 was applied to evaluate the quality of the included literature. We used Stata 16.0 to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and plot summary receiver operating characteristic curve, as well as to assess diagnostic accuracy using the area under the curve (AUC). A total of 25 studies, including 1980 patients and 2345 controls, were included in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 were 0.58 (95% CI 0.52-0.63), 0.95 (95% CI 0.92-0.97), 11.57 (95% CI 6.88-19.48), 0.45 (95% CI 0.39-0.51), 25.92 (95% CI 14.84-45.26), and 0.80 (95% CI 0.76-0.83), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of CA125 were 0.41 (95% CI 0.34-0.49), 0.91 (95% CI 0.85-0.95), 4.55 (95% CI 2.73-7.58), 0.65 (95% CI 0.57-0.74), 7.03 (95% CI 3.92-12.62), and 0.68 (95% CI 0.64-0.72), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 + CA125 were 0.67 (95% CI 0.60-0.73), 0.92 (95% CI 0.87-0.95), 8.59 (95% CI 5.32-13.86), 0.36 (95% CI 0.30-0.44), 23.80 (95% CI 13.86-40.86), and 0.85 (95% CI 0.82-0.88), respectively. This Meta-analysis found that HE4 alone or in combination with CA125 showed better diagnostic efficacy than CA125, regardless of clinical stage and pathological type. HE4 + CA125 had slightly higher diagnostic efficiency than HE4, but did not show significant advantages. While the studies were heterogeneous, the credibility of the findings needs to be further confirmed by more homogeneous, prospective, and large sample size studies.

Association between serum HE4 and poor periodontal health in adult women

ObjectivesThe aim of this study is to explore the association between serum human epididymal protein (HE4) levels and poor periodontal health.Materials and methodsData used in our study from the National Health and Nutrition Examination Survey (NHANES) 2001–2002 and Gene Expression Omnibus database (GSE10334 and GSE16134). Periodontitis category was defined by the 2017 classification scheme based on clinical periodontal parameters. Univariate and multivariate logistic regression analyses were used to explore the relationship between serum HE4 levels and the risk of periodontitis. GSEA analysis was performed to investigate the function of HE4.ResultsA total of 1715 adult women over the age of 30 were included in our study. Compared with the lowest tertile, individuals in the highest tertile of HE4 levels were more likely to be Stage III/IV periodontitis (ORtertile3vs1 = 2.35, 95% CI: 1.35–4.21). The association was still significant in populations who were less than 60 years old, non-Hispanic white, high school graduate, 1.3 < PI ≤ 3.5, non-smoker, current smoker, non-obese, obese, and who had not diabetes mellitus or had not hypertension. In addition, HE4 expression was upregulated in diseased gingival tissues and involved in cell proliferation and immunity.ConclusionsSerum HE4 is positively associated with poor periodontal health in adult women.Clinical relevancePatients with high serum HE4 levels are more likely to have Stage III/IV periodontitis. HE4 has the potential to be used as a biomarker to predict the severity of periodontitis.

Elevated serum levels of human epididymis protein 4 in adult patients with proliferative lupus nephritis.

This study aimed to access whether serum human epididymis protein 4 (HE4) level could identify lupus nephritis (LN) pathological classes in adults and children. The serum HE4 levels of 190 healthy subjects and 182 patients with systemic lupus erythematosus (SLE) (61 adult-onset LN [aLN], 39 childhood-onset LN [cLN], and 82 SLE without LN) were determined using Architect HE4 kits and an Abbott ARCHITECT i2000SR Immunoassay Analyzer. Serum HE4 level was significantly higher in the aLN patients (median, 85.5 pmol/L) than in the patients with cLN (44 pmol/L, P < 0.001) or SLE without LN (37 pmol/L, P < 0.001), or the healthy controls (30 pmol/L, P < 0.001). Multivariate analysis showed that serum HE4 level was independently associated with aLN. Stratified by LN class, serum HE4 level was significantly higher in the patients with proliferative LN (PLN) than in those with non-PLN, and this difference was found only in aLN (median, 98.3 versus 49.3 pmol/L, P = 0.021) but not in cLN. Stratified by activity (A) and chronicity (C) indices, the aLN patients with class IV (A/C) possessed significantly higher serum HE4 levels than those with class IV (A) (median, 195.5 versus 60.8 pmol/L, P = 0.006), and this difference was not seen in the class III aLN or cLN patients. Serum HE4 level is elevated in patients with class IV (A/C) aLN. The role of HE4 in the pathogenesis of chronic lesions of class IV aLN needs further investigation.

Is Serum Human Epididymis Protein HE4, More Specific than Cancer Antigen 125 in Patients with Benign Gynecological Diseases?

Background: The cancer antigen 125 “CA125” and Human Epididymis protein 4 “HE4” are among some well worked out markers for recognition of malignancy in ovarian tumors. Their different cutoffs are determined and reported by various studies and mostly used recommended cutoffs are 35.0 U/mL for CA125 and 140pmol/L for HE4. They are both reported to recognize the malignancy well, but how specific they are for benign gynecological diseases is still needed to be worked out. Aim: To determine and compare the performance of CA125 and HE4 for benign gynecological pathologies. Methodology: A cross-sectional study was performed at Gajju Khan Medical College in collaboration with Armed forces Institute of pathology (AFIP). A total of 76 women of age above 18 years age, with benign ovarian pathology, confirmed through histological evaluation were enrolled. All these were examined on both markers, i.e. CA125 and HE4. Standard cutoffs of CA125 &gt;35.0 U/mL and HE4&gt;140 pmol/L were used to see if the case was labeled malignant, incorrectly. SPSS 20.0 was used to manage and analyze the data. Performance of the two markers were compared by using some descriptive analysis and using chi-square test. P-value ≤0.05 was considered significant. Results: The median age of these women was 40 years ranging between 18 and 71. Majority (86.8%) was premenopausal, The CA125 had no difference between pre and post-menopausal women but HE4 had a significant difference with p-value 0.029. there were 10.5% incorrect labeling of malignancy when evaluated for CA125, while only 2.6% incorrect on HE4. This difference was found statistically significant between two markers with p-value 0.05. Conclusion: HE4 is better and more specific marker for benign gynecological pathologies as compared to CA125 Keywords:Benign Ovarian Epithelial, Human epididymisprotein (HE4), Cancer Antigen 125 (CA125), Specificity

Serum Human Epididymis Protein 4 as a Prognostic Predictor of New-Onset Heart Failure among Women after Acute Coronary Syndrome: A Single-Center Retrospective Study

Introduction: Little is known about the prognostic factors among women with acute coronary syndrome (ACS), partly due to the small number of women included in heart failure (HF) clinical trials. Human epididymis protein 4 (HE4) has been proven to be a new biomarker for acute and chronic HF over the years. We hypothesize that HE4 could be a promising predictor. Methods: This retrospective study analyzed data from Zhejiang Provincial People’s Hospital. This study included 302 female patients with ACS between January 1, 2021, and December 1, 2021. The primary outcome was new-onset HF after ACS during the 12-month follow-up period. We used a logistic regression model to evaluate the association between serum HE4 levels and the incidence of HF. Serum HE4 levels were measured at baseline (within 24 h after admission). Results: Of the 302 female patients, 70 (23.2%) developed new-onset HF within 12 months. Serum HE4 levels in patients with adverse events were significantly higher than those in patients without events (8.9 [7.3–11.5] pmol/dL versus 5.9 [5.0–6.8] pmol/dL, p < 0.001). The levels of HE4, troponin I peak, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR) were validated as independent predictors, with HE4 being the best laboratory predictor (area under the curve, 0.863; 95% confidence interval, 0.817–0.909). Serum HE4 concentrations of >6.93 pmol/dL distinguished patients at risk of HF with 82.9% sensitivity and 78.0% specificity (maximum Youden index J, 0.609). Moreover, HE4 levels were associated with an increased risk of HF. Discussion: We found a strong relationship between HE4 and the occurrence of HF after ACS among women, which might help identify patients at high risk of HF for whom close or intense management should be mandatory.

Retracted: Application Value of Real-Time Ultrasonic Elastograph with Serum Human Epididymis Protein 4, Interleukin-33, and Carbohydrate Antigen 153 in Diagnosis of Early Cervical Cancer.

[This retracts the article DOI: 10.1155/2022/4880874.].

Development of a prediction model for gross residual in high-grade serous ovarian cancer by combining preoperative assessments of abdominal and pelvic metastases and multiparametric MRI

To preoperatively predict residual tumor (RT) in patients with high-grade serous ovarian carcinoma (HGSOC) via a radiomic-clinical nomogram. A total of 128 patients with advanced HGSOC were enrolled (training cohort: n=106; validation cohort: n=22). Serum cancer antigen-125 (CA125), serum human epididymis protein 4 (HE-4) level, and neutrophil-to-lymphocyte ratio (NLR) were obtained from the medical records. Metastases in abdomen and pelvis (MAP) of HGSOC patients was evaluated and scored based on preoperative abdominal and pelvic enhanced CT, MRI and/or PET-CT. A volume of interest (VOI) of each tumor was manually contoured along the boundary slice-by-slice. Radiomic features were extracted from the T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) images. Univariate and multivariate analyses were used to determine the independent predictors of RT status. Least absolute shrinkage and selection operator (LASSO) logistic regression was performed to select optimal features and construct radiomic models. A radiomic-clinical nomogram incorporating radiomic signature and clinical parameters was developed and evaluated in training and validation cohorts. MAP score (p=0.002), HE-4 level (p=0.001) and NLR (p=0.008) were independent predictors of RT status. The final radiomic-clinical nomogram showed satisfactory prediction performance in training (AUC=0.936), cross validation (AUC=0.906) and separate validation cohorts (AUC=0.900), and fitted well in calibration curves (p > 0.05). Decision curve further confirmed the clinical application value of the nomogram. The proposed MRI-based radiomic-clinical nomogram achieved excellent preoperative prediction of the RT status in HGSOC.

A nomogram model based on clinical markers for predicting malignancy of ovarian tumors.

The aim of this study was to build a nomogram based on clinical markers for predicting the malignancy of ovarian tumors (OTs). A total of 1,268 patients diagnosed with OTs that were surgically removed between October 2017 and May 2019 were enrolled. Clinical markers such as post-menopausal status, body mass index (BMI), serum human epididymis protein 4 (HE4) value, cancer antigen 125 (CA125) value, Risk of Ovarian Malignancy Algorithm (ROMA) index, course of disease, patient-generated subjective global assessment (PG-SGA) score, ascites, and locations and features of masses were recorded and analyzed (p 0.05). Significant variables were further selected using multivariate logistic regression analysis and were included in the decision curve analysis (DCA) used to assess the value of the nomogram model for predicting OT malignancy. The significant variables included post-menopausal status, BMI, HE4 value, CA125 value, ROMA index, course of disease, PG-SGA score, ascites, and features and locations of masses (p 0.05). The ROMA index, BMI (≥ 26), unclear/blurred mass boundary (on magnetic resonance imaging [MRI]/computed tomography [CT]), mass detection (on MRI/CT), and mass size and features (on type B ultrasound [BUS]) were screened out for multivariate logistic regression analysis to assess the value of the nomogram model for predicting OT malignant risk (p 0.05). The DCA revealed that the net benefit of the nomogram's calculation model was superior to that of the CA125 value, HE4 value, and ROMA index for predicting OT malignancy. We successfully tailored a nomogram model based on selected clinical markers which showed superior prognostic predictive accuracy compared with the use of the CA125, HE4, or ROMA index (that combines both HE and CA125 values) for predicting the malignancy of OT patients.

Diagnostic accuracy of serum human epididymis protein 4 in ovarian cancer patients with different ethnic groups and menopausal status: a meta-analysis and systematic evaluation.

We aimed to analyze and evaluate the diagnostic value of serum human epididymis protein 4 (HE4) in ovarian cancer (OC) of patients with different menopausal status. A comprehensive electronic and manual search of the relevant literature was performed through several databases such as CNKI, Wanfang database, VIP database, Chinese biomedical database, web of science, PubMed, EMBASE, and Cochrane database. We collected Chinese and English articles to assess the diagnostic value of HE4 for ovarian cancer in female with different menopausal status. The quality of the studies included in the systematic review was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. A total of 14 publications were included in this study and we didn't find publication bias in them. The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of HE4 for the diagnosis of ovarian cancer in postmenopausal vs. premenopausal female were 0.71 (95% CI, 0.63-0.78) vs 0.78 (95% CI, 0.74-0.81); 0.91 (95% CI, 0.85-0.95) vs 0.90 (95% CI, 0.86-0.93); 11.90 (95% CI, 6.42-22.07) vs 11.03 (95% CI, 6.44-18.89); and 0.30 (95% CI, 0.22-0.39) vs 0.24 (95% CI, 0.20-0.29), respectively. Serum HE4 has greater diagnostic value in detecting ovarian cancer, especially in Asian postmenopausal female.

The Diagnostic Accuracy of Serum and Urine Human Epididymis Protein 4 (HE4) in Ovarian Cancer in 15,394 Subjects: An Updated Meta-Analysis.

Background We aim to determine the diagnostic accuracy of both serum and urinary human epididymis protein 4 (HE4) in the diagnosis of ovarian cancer. Methods Electronic databases and search engines such as PubMed, Cochrane Library, and Google Scholar were searched systematically by two independent reviewers to retrieve articles published from inception to June 11, 2022. The diagnostic accuracy of serum and urinary HE4 was computed using the random-effects model in terms of pooled sensitivity, pooled specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). To explain any source of possible heterogeneity, meta-regression and subgroup analyses were performed. Risk of bias assessment was conducted using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tools recommended by the Cochrane Library. Result and conclusion This meta-analysis included a total of 38 studies of serum HE4 involving 14,745 subjects and five studies for urinary HE4 involving 649 subjects. We observed acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROC), and diagnostic odds ratio (DOR) at 0.79 (95% CI: 0.75-0.82), 0.92 (95% CI: 0.87-0.95), 0.88 (95% CI: 0.85-0.91), and 43 (95% CI: 25-72), respectively, for serum HE4 for discriminating ovarian cancer. For urine HE4, the pooled sensitivity, specificity, SROC, and DOR were 0.80 (95% CI: 0.64-0.90), 0.93 (95% CI: 0.83-0.98), 0.94 (95% CI: 0.91-0.95), and 55 (95% CI: 15-198), respectively. Therefore, HE4 is a promising biomarker with a high degree of specificity and acceptable sensitivity for the diagnosis of ovarian cancer. Registration number This meta-analysis was performed after the registration of the protocol in the PROSPERO database with registration numberCRD42022324947.

Sulfur hexafluoride microbubbles combined with serology distinguish benign and malignant ovarian tumors

To explore the value of contrast-enhanced ultrasound with Sulfur hexafluoride microbubbles, serum carbohydrate antigen 125, carcinoembryonic antigen and human epididymis protein 4 joint inspection in the differential diagnosis of ovarian tumors. A total of 56 patients with ovarian tumors were chosen as research materials from June 2018 to October 2021. Result show 24 patients of benign tumors and 32 patients of malignant tumors were confirmed by pathological diagnosis. The rise time and time to peak values of malignant tumors were lower than those of benign tumors (p&lt;0.001). However, peak intensity, Time intensity curve -Area under Curve and serum human epididymis protein 4, carcinoembryonic antigen, carbohydrate antigen 125 levels joint inspection in malignant tumors were higher than those in benign tumors (p &lt; 0.001). Rise time, peak intensity and time to peak in benign and malignant ovarian tumors were 0.895 (0.802–0.999, 95% CI), 0.852 (0.804–0.916, 95% CI), 0.907 (0.829–0.925, 95% CI), respectively. Area under Curve were 0.909 (0.846–1.012, 95% CI) and serum carbohydrate antigen 125 and carcinoembryonic antigen and human epididymis protein 4 for diagnosis of benign and malignant ovarian tumors were 0.865 (0.838–0.991, 95% CI), 0.816 (0.702–0.930, 95% CI), 0.903 (0.850–1.007, 95% CI). Contrast-enhanced Ultrasound unite to serum carbohydrate antigen 125 and carcinoembryonic antigen and human epididymis protein 4, the accuracy rate 92.86% (52/56) significantly higher than Contrast-enhanced Ultrasound or serum v diagnosis benign and malignant of ovarian tumor (p&lt;0.01, 92.86% vs. 82.14%, p&lt;0.001, 92.86% vs. 73.21%). Conclusion Contrast-enhanced Ultrasound, carbohydrate antigen 125, carcinoembryonic antigen, human epididymis protein 4 joint inspection can improve the accuracy of early ovarian cancer.

Elevated serum human epididymis protein 4 is associated with disease severity and worse survival in idiopathic pulmonary fibrosis: a cohort study.

BackgroundElevated expression of human epididymis protein 4 (HE4) was previously described in connective tissue disease-associated interstitial lung diseases (CTD-ILDs) and cystic fibrosis (CF), but the clinical significance of HE4 has remained unknown in idiopathic pulmonary fibrosis (IPF), which is a progressive fibrosing ILD with a heterogeneous course that is in urgent need of reliable biomarkers in its clinical practice.MethodsA total of 27 IPF patients with acute exacerbation status (AE-IPF), 32 IPF patients with stable status (S-IPF), and 29 sex-age matched healthy controls were retrospectively included. The levels of serum HE4 and Krebs von den Lungen-6 (KL-6) of the 3 cohorts were measured. In addition, the pulmonary expression of HE4 was evaluated in lung transplant specimens of IPF using immunohistochemistry and Western blot, and noncancerous lung tissue resected from early-stage lung cancer patients as controls. The endpoint of follow-up was March 1st, 2022, and the Cox regression model was used to analyze the prognostic value of HE4.ResultsThe levels of HE4 and KL-6 were obviously elevated in AE-IPF patients compared to S-IPF (296.4 vs. 178.1 pmol/L for HE4, P<0.001; 2,007.0 vs. 990.5 IU/mL for KL-6, P<0.001) or healthy controls (296.4 vs. 51.8 pmol/L for HE4, P<0.001; 2,007.0 vs. 181.0 IU/mL for KL-6, P<0.001). Significant correlations were observed between serum HE4 levels and percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) (r=−0.526, P<0.001), percent predicted forced vital capacity (FVC%) (r=−0.344, P=0.024), gender-age-physiology (GAP) index (r=0.535, P<0.001), and oxygenation index (r=−0.550, P<0.001) in IPF patients. In histological analysis, overexpression of HE4 in mucosal epithelium of dilated bronchi was observed in IPF patients compared with controls. Multivariate cox regression revealed that serum levels of HE4 [hazard ratio (HR) =1.004, P=0.042] and GAP index (HR =1.374, P=0.010) were associated with worse survival in IPF patients.ConclusionsThe expression of serum HE4 was obviously elevated in IPF patients, especially in AE-IPF patients. In addition, serum HE4 could be utilized as a biomarker of disease severity and poor prognosis of IPF patients. These findings warrant further validation in larger, multi-center, and longitudinal cohorts.

Comparative study of significance of serum human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) as an early tumour marker in female patients with ovarian cancer

Aim: To determine the usefulness of serum human epididymis protein4 (HE4) along with Carbohydrate Antigen 125 (CA125) as an early tumour marker in female patients with ovarian cancer.Method: The ovarian cancer patients were recruited from OPD/IPD of Surgery and Oncology department of SMS Hospital, and evaluated serum HE4 and CA125. Total 262 subjects were included in this study.131 ovarian cancer Patients were divided according to different stages and 131 control subjects also included.Results: Serum HE4 and CA125 level raised significantly in ovarian cancer patients. Further increases with the advanced stage of the ovarian cancer.Conclusion: Both HE4 and CA125 can be useful diagnostic tumour marker in ovarian cancer.