Human Epididymis Protein 4 Concentrations Research Articles

Evaluation of serum human epididymis protein 4 in patients with relapsing-remitting multiple sclerosis

So far, little is known about the properties of human epididymis protein 4 (HE4) in multiple sclerosis (MS). This type 4 glycoprotein belongs to a family of genes encoding proteins whose expression is associated with the process of spermatogenesis in the epididymis. The biological function of HE4 is not fully understood. Overexpression of HE4 has been found in several malignant tumors, particularly in ovarian cancer, as well as in mesothelioma, lung, endometrial, breast, and kidney cancers. To evaluate serum HE4 in patients with relapsing-remitting multiple sclerosis (RRMS) as compared to healthy controls. Fifty patients with RRMS undergoing first-line immunomodulatory treatment were enrolled in the prospective study. We analyzed correlations between serum HE4 levels and gender, age, disease duration, the Expanded Disability Status Scale (EDSS), annualized relapse rate (ARR), and magnetic resonance imaging (MRI) lesions. The patients from the study group had higher concentrations of HE4 than the subjects from the control group. Patients with EDSS > 2 had significantly higher concentrations of HE4. Positive correlations were found between HE4 concentrations and age as well as between HE4 concentrations and disease duration. No significant correlations were found between HE4 concentrations and EDSS or between HE4 concentrations and ARR. The results of the study indicate a novel aspect of the HE4 protein in the pathomechanisms of MS.

An association of circulating Tregs and Th17 cells producing IL-21 and IL-22 with the ROMA in ovarian cancer patients

The purpose of the present study was to assess the association of regulatory T cells (Tregs; CD4+ FOXP3+) and helper T lymphocytes (Th17) releasing interleukin (IL)-21 and IL-22, with the Risk of Ovarian Malignancy Algorithm (ROMA). Similar association was made with two additional tumour markers, human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) from patients serum. The presence of Tregs and Th17 was determined both in the peripheral blood and in the tissue of epithelial ovarian tumors. Mononuclear cells obtained from patient’s peripheral blood (PBMCs) and from ovarian tissue were isolated by density gradient centrifugation. As a control group patients who had undergone surgery for infertility without ovarian pathology were selected. The percentage of Tregs and Th17 releasing IL-21 or IL-22 cells from both peripheral blood and tumor tissue was measured by flow cytometry. No differences in demographic parameters like body mass index, age, or gravidity were observed among the studied groups. However, an increased concentration of marker HE4 and value of ROMA was identified in individuals with ovarian cancer when compared with women with cystadenomas. Furthermore, a negative correlation between the ROMA value in the serum and Tregs from the peripheral blood of patients with cystadenoma ovarian tumors was detected. The presented work documents, for the first time, the negative association between peripheral blood Tregs and ROMA evaluation based on the tumour markers present in the serum of women with ovarian cystadenoma. Such an effect might result from the negative impact of Tregs on the inflammation process and on tumorigenesis caused by the persistent inflammation.

Markedly Elevated HE4 in Hepatic Neuroendocrine Neoplasm: A Report of Two Cases and Literature Review

Introduction: Human epididymis protein 4 (HE4) is a secretory protein encoded by the whey-acidic four-disulfide core domain protein 2 (WFDC2) gene. Clinically, HE4 is an important serological biomarker used to detect and monitor epithelial ovarian cancer. Although elevated in a high percentage of patients with ovarian and endometrial cancer, high serum HE4 levels may also be detected in patients with other various non-gynecologic malignant disorders such as lung adenocarcinoma and breast cancer. However, the association between high HE4 and hepatic neuroendocrine neoplasms (HNENs) remains unknown. Case Presentation: Herein, two patients with HNENs and elevated serum HE4 are presented. Both cases were old women who underwent pelvic examination and ultrasonography and the results were normal. Immunohistochemistry assays demonstrated high HE4 expression in neuroendocrine carcinoma, whereas no HE4 expression was observed in hepatocellular carcinoma and clear cell renal cell carcinoma liver metastases. Conclusions: This preliminary observation suggested HE4 concentrations may be elevated in neuroendocrine neoplasm patients with no ovarian cancer. Thus, HE4 results should be interpreted cautiously in female patients with HNENs. In addition, this preliminary observation suggested the need to perform further studies to assess the implications of our results in terms of the potential role of HE4 as a serum biomarker in the diagnosis and prognosis of HNEN patients.

Dual-label time-resolved fluoroimmunoassay for simultaneous measurement of human epidermal growth factor receptor 2 and human epididymis protein 4 in serum

In this study, a novel dual-label time-resolved fluoroimmunoassay (TRFIA) is described for simultaneous quantification of human epidermal growth factor receptor 2 (HER-2) and human epididymis protein 4 (HE4) in serum to screen gynecologic cancers. A double-antibody sandwich TRFIA was introduced with europium and samarium chelates to simultaneously detect the concentrations of HER-2 and HE4. Under optimal conditions, the proposed method exhibited wide linear ranges for HER-2 of 0.07–500 ng ml−1 and for HE4 of 0.32–1000 pmol l−1 with the average coefficient of variation below 10%. The specificity was satisfied through determining the other common tumor markers. The recovery rates were 94.5% and 96.6% on average for HER-2 and HE4, respectively. Good correlations were observed in clinical samples between developed method and commercial chemiluminescence immunoassay kits. The results demonstrated that dual-label TRFIA for HER-2 and HE4 was rapid and precise, and therefore could have a promising use in large sample detection for gynecological cancer screening.

Comparison of the clinical significance of serum HE4, CA125 and ROMA in the differential diagnosis of ovarian tumor

Objective To compare the clinical significance of human epididymis protein 4(HE4), CA125, ROMA in the differential diagnosis of ovarian cancer. Methods From May 2016 to October 2017, 240 patients with ovarian tumor in Xuzhou Cancer Hospital were selected.According to the result of postoperative pathology, the patients were divided into benign ovarian disease group(n=120) and ovarian cancer group(n=120). And 100 healthy women from medical examination center were selected as control group.The electrochemiluminescence (ECLIA) technique was used to assess the serum levels of CA125, HE4, and ROMA was calculated.The clinical significance of HE4, CA125, ROMA in the differential diagnosis of ovarian cancer was analyzed by statistic methods. Results The CA125, HE4 concentrations and ROMA in the ovarian cancer group[(370.9±213.2)U/mL, (364.4±227.0)pmpl/L, (80.2±26.1)%]were higher than those in the benign ovarian disease group and the health control group(all P<0.01), there were no statistically significant differences between the benign ovarian disease group and the healthy control group(P=0.356, P=0.321, P=0.292). The sensitivity, specificity, positive and negative predictive values, accuracy of ROMA were higher than those of HE4 and CA125.By using the ROC analysis, the AUC for CA125, HE4, ROMA were 0.832, 0.888, 0.960, respectively, AUC(CA125)<AUC(HE4)<AUC(ROMA). Conclusion CA125 and HE4 have important value in the diagnosis of ovarian cancer, but the ROMA shows the best diagnostic performance and actual value. Key words: Ovarian neoplasms; CA-125 antigen; Human epididymis protein 4; ROC curve; Diagnosis, differential; ROMA

Role of Human Epididymis Protein 4 (HE4) in Determining Survival of Patients With Endometrial Cancer: A Meta-Analysis.

Background:Human epididymis protein 4 (HE4) is a novel cancer biomarker. This study evaluates the prognostic role of HE4 in determining the survival of endometrial cancer patients.Methods:Literature search was conducted in electronic databases (Embase, Ovid, PubMed, Scopus, and Web of Science). Studies were selected if they reported the relationship between HE4 and the survival of endometrial cancer patients. Random-effects meta-analyses were performed to achieve estimates of baseline serum HE4 levels, the 5-year survival with high and low serum HE4 levels/expression, and the hazard ratios (HRs) of the survival between patients with high and low serum HE4 levels.Results:9 studies (1404 patients; age 63.1 years [95% confidence interval (CI): 61.2, 64.9]; follow-up 35.9 months [95% CI: 32.2, 39.6]) were included. In these patients, serum HE4 levels were 83.36 picomole/liter (pM) [95% CI: 70.15, 96.56] overall but these were higher in patients with recurrence (108.13 pM [95% CI: 63.09, 153.18] and lower in patients with no recurrence (67.88 pM [95% CI: 65.09, 70.67]). The 5-year overall survival rate was higher in patients with low HE4 levels/expression (86% [95% CI: 79, 92] but lower in patients with high HE4 levels/expression (63% [95% CI: 58, 68]. A pooled HR of survival between patients with high and low serum HE4 levels of 2.25 [95% CI: 1.56, 2.94] indicated shorter survival in patients with high serum HE4 levels.Conclusion:High HE4 concentrations in patients with endometrial cancer are found to be associated with shorter survival.

Diagnostic value of human epididymis protein 4 in malignant pleural effusion in lung cancer

This study aimed to assess the diagnostic value of human epididymis protein 4 (HE4) in the pleural effusion of lung cancer patients. HE4 protein in the pleural effusion of 60 lung cancer patients was measured by electrochemiluminescence, in parallel with those from 56 patients with benign lung disease, and the association with malignant pleural effusion was evaluated. The level of HE4 in samples from lung cancer patients was significantly higher than the level for those with benign lung lesions (P=0.001) and patients with lung adenocarcinoma showed significantly higher levels of HE4 than those with squamous cell carcinoma and small cell carcinoma (P=0.002 and P=0.034, respectively). Using an optimal threshold of 652.2 pmol/L, the HE4 level distinguished malignant lung cancer from benign lesions with a sensitivity of 78.3% and a specificity of 75.0%. Moreover, the HE4 level differentiated adenocarcinoma from benign lesions with a sensitivity of 75.9% and a specificity of 85.7% when a threshold of 744.05pmol/L was used. However, there was no significant difference in the 2year survival rates of lung cancer patients with high and low HE4 concentrations in pleural fluid (P=0.882). In addition, there was no significant difference in HE4 levels between tuberculous and inflammatory pleural effusions (P=0.309). HE4 in the pleural fluid of lung cancer patients can be valuable in the diagnosis of malignant pleural effusion; however, it does not correlate with the prognosis of patients.

Human Epididymis Protein 4 (HE4) Reference Limits in Polish Population of Healthy Women, Pregnant Women, and Women with Benign Ovarian Tumors.

Objectives Defining precisely the normal range of HE4 protein is crucial for the proper interpretation of tumor marker results and for a more efficient diagnosis of ovarian malignancy. The aim of our study was to evaluate a reference limit of HE4 protein in a population to promote and facilitate the common use of HE4 protein assays. We also tried to identify potential association of HE4 levels with other conditions such as smoking, age, BMI, and creatinine levels. Methods Blood samples were collected from 617 patients divided into three groups: healthy, pregnant, and with benign ovarian tumors. Serum HE4 concentrations were measured following a standard procedure. HE4 reference ranges for each group and association of HE4 levels with BMI, creatinine, and smoking were investigated. Results HE4 reference limit for healthy patients equals 85 pmol/l, which becomes 73 pmol/l and 93 pmol/l for pre and postmenopausal subgroups, respectively. There is a statistically significant correlation between HE4 serum level and smoking (p = 0.000001) and there is no correlation with creatinine. But if we take into account age and smoking, in multivariate analysis, there is a correlation. For pregnant, the upper limit values of normal HE4 levels are 55 pmol/l (median = 40 pmol/l), 80 pmol/l (median = 43 pmol/l), and 106 pmol/l (median = 53 pmol/l) for the first, second, and third trimesters, respectively. Conclusions HE4 protein value strongly depends on the patient's age and smoking. The serum concentration of HE4 marker increases with the duration of pregnancy. Understanding the normal range of HE4 protein enables the correct interpretation of marker measurements. This may result in an earlier and more effective diagnosis of ovarian cancer.

Human Epididymis Protein 4 Quantification and Interaction Network Analysis in Seminal Plasma.

A well-known tissue marker of ovarian cancer, Human Epididymis protein 4 (HE4) is the member of whey acidic four-disulfide core proteins family. Purified from human seminal plasma and characterized as a cross-class protease inhibitor, HE4 was proposed to shield spermatozoa against proteolytic factors. However, its exact biological function is unknown. Proteins usually function in conjunction with other proteins in the system and thus, identification and analysis of protein networks become essential to decode protein functions. This study was performed to explore possible role(s) of HE4 in reproductive physiology via identification of its interactome in human seminal plasma. HE4 binding proteins were identified through co-immunoprecipitation and MALDITOF/ MS analysis. Also, HE4 was quantified by ELISA in fertile and infertile human seminal plasma samples. Ten HE4 binding proteins were identified, viz. protein phosphatase 1 regulatory subunit 21, protein kinase CLK3, Ankyrin repeat domain-containing protein36A, prostatic acid phosphatase, KIF5C, Spectrin repeat containing, nuclear envelope 1, isoform CRAf, tropomyosin 4, vezatin, utrophin and fibronectin1. This interaction network suggests that HE4 plays multiple roles, specifically in capacitation, sperm motility and maturation. Further, HE4 concentration in human seminal plasma samples was determined by Elisa. Higher HE4 expression in normozoospermia compared to azoospermia and asthenozoospermia affirms its importance in fertilization. Based on identified interactome, it is plausible that HE4 plays a crucial role in fertilization, specifically in sperm maturation, motility and capacitation.

Trimetallic hybrid nanodendrites and magnetic nanocomposites-based electrochemical immunosensor for ultrasensitive detection of serum human epididymis protein 4

Alloy nanomaterials with various morphologies have showed their potential application in electrochemical signal amplification. However, it is still challenging to fabricate stable multimetallic nanomaterials with large surface area and strong electrochemical activity for the further enhancement of electrochemical sensors’ performance. Here, the trimetallic AgPtCo nanodendrites (NDs) were synthesized as powerful redox probe and highly efficient signal amplifier for electrochemical signal readout. A robust and ultrasensitive electrochemical immunosensor, based on AgPtCo NDs and magnetic nanocomposites (Fe3O4@SiO2@Au MNCs), was successfully developed to detect serum human epididymis protein 4 (HE4). The established method, drawing upon the strong electrochemical activity of AgPtCo NDs and the enrichment and separation effect of MNCs, exhibited a wide linear range (0.001–50 ng mL−1) and a low detection limit (0.487 pg mL−1). Besides, the developed sensor was applied to analyze the concentration of HE4 in real samples and the results achieved were consistent with those of clinical methods. Thus, this AgPtCo NDs and MNCs based electrochemical immunosensor might become a powerful alternative approach for ultrasensitive detection of various serum biomarkers associated with early diagnosis and treatment of diseases.

C60 Mediated Ion Pair Interaction for Label-Free Electrochemical Immunosensing with Nanoporous Anodic Alumina Nanochannels.

Label-free biosensing based on the nanoporous anodic alumina (NAA) membrane emerged as a versatile biosensing platform in the recent decade. In the present work, we developed a new immunosensing strategy based on the nanochannels of NAA and the ion pair interaction mediated by electrochemistry of C60. The NAA served as the matrix for the immobilization of the capture antibodies. The incubation of target antigens resulted in the formation of the immunocomplexes and thus an increase of the steric hindrance of the nanochannels. Therefore, the concentration of the redox probe transported through the nanochannels decreases, which can be detected at the working electrode modified with C60. Herein, we initially found that the cathodic peak ascribed to the reduction of C60 to C60- was obviously enhanced by the presence of the redox probe K3[Fe(CN)6] and which was contributed to the formation of a ternary ion association complex among C60, tetraoctylammonium bromide, and K3[Fe(CN)6]. Therefore, the transportation of K3[Fe(CN)6] though the NAA-based bionanochannels can be detected by a C60 modified electrode with an amplified signal. Choosing human epididymis protein 4 (HE4) as the model target, a linear range of 1.0 ng mL-1 to 100 ng mL-1 can be established between the peak current obtained from the differential pulse voltammetric response of the platform and the concentration of HE4. The detection limit was 0.2 ng mL-1. This study not only provides a new avenue to develop the other nanochannel-based biosensing platform for a variety of other disease biomarkers but also contributes to the electrochemistry of fullerene.

The value of human epididymis protein 4 (HE4) as a serum tumor marker for accurate bone metastases finding by whole-body bone scintigraphy in lung cancer patients

The aim of our study was to correlate the serum concentration of human epididymis protein 4 (HE4) in lung cancer patients with the bone metastases detected by whole-body bone scintigraphy. The serum concentrations of HE4 were determined by electrochemiluminescence immunoassay method in 60 patients with lung cancer and in 10 persons without malignant disease (control group). All participants were examined by whole-body bone scintigraphy with hybrid gamma camera of type BrightView XCT. We found bone metastases in 25.0% of patients by whole-body bone scintigraphy and probable bone metastases in 18.3% of patients. We did not observe bone metastases in 56.7% of patients and in nobody from control group. We observed that 73.33% patients with bone metastases had more than 3 bone metastasis deposits. Patients had significantly increased concentration of HE4 (p < 0.0001). All three subgroups of patients (bone metastases, probable bone metastases, no evidence of bone metastases) had significantly increased concentration of HE4 compared to controls. The highest concentration of HE4 had 9 patients with small-cell lung cancer of whose 4 patients had bone metastases, 4 patients had probable bone metastases and one patient was with no evidence of bone metastases. We found that HE4 has a discriminatory ability to differentiate groups of patients and healthy controls, as well as within scaffold scintigraphy in patients with lung cancer (p = 0.0002). The serum concentration of human epididymis protein 4 was significantly increased in patients with lung cancer in comparison with persons of control group. A quarter of lung cancer patients had identified bone metastases by whole-body bone scintigraphy and approximately 20% of patients had probable bone metastases. The increasing serum concentrations of human epididymis protein 4 can have importance in the diagnosis of bone metastases in patients with lung cancer, in particular in small-cell lung cancer.

Serum human epididymis protein 4 vs. carbohydrate antigen 125 in ovarian cancer follow-up

BackgroundThe addition of human epididymis protein 4 (HE4) to carbohydrate antigen 125 (CA125) in ovarian cancer (OC) assessment has been proposed. We compared the clinical value of biomarker changes in a prospective series of patients undergoing OC monitoring. MethodsWe studied 43 patients (79% post-menopausal), followed for 3.5 ± 3.1 years. Serous OC was prevalent (53.5%), with 81.4% of patients diagnosed at late stages. Both cut-offs and reference change values (RCV) were used for assessing significant marker changes. ResultsThe use of cut-offs for CA125 and HE4 interpretation appeared equally fitting the evaluation of disease progression defined according to running guidelines, performing better than RCV criterion. However, both markers were simultaneously over cut-offs only in 46% of samples and changed in agreement in 35% of cases. The inspection of individual longitudinal trends indicated as main causes of disagreement the influence of renal impairment on HE4 concentrations and the more significant rate of decrease of CA125 vs. HE4 concentrations early after treatment. CA125 and HE4 changes according to RCV were not predictive of OC progression. ConclusionsCA125 appears the most reliable biomarker for OC monitoring, whereas HE4 contributes additional information only in a minority of cases.

Establishment and performance evaluation of a domestic chemiluminescence immunoassay of serum HE4

Objective To establish and evaluate a domestic Chemiluminescence immunoassay(CLIA) for detecting serum human epididymis protein4(HE4). Methods To establish a double antibody sandwich CLIA for the determination of serum HE4. Fluorescein isothiocyanate (FITC) and alkaline phosphatase (ALP) were used to label two different monoclonal antibodies of HE4. The separation could be realized by the magnetic particles coated with anti-FITC antibodies. Measure the relative light unit (RLU) after adding substrate solution, the RLU is proportional to the concentration of HE4. After evaluating the analytical performance including sensitivity, precision, accuracy, linearity, specificity under the optimized condition, this study compared the method with the commerical HE4 kits as well. Results The precision of with-in lot , and with-out lot are less than 4.0% and 5.0% respectively; Recovery is within 90.0%-110.0%; LoB is 5.0 pmol/L; functional sensitivity is 15.0 pmol/L; measure range is 15.0-1 500.0 pmol/L; the Correlation coefficient is bigger than 0.99 comparing with commercial kits. The AUC(area under curve) of three methods is 0.895, 0.900 and 0.896 respectively. Conclusions This study established a sensitive CLIA method with high repeatability and wide measure range; it has good correlation with commercial HE4 test kits.(Chin J Lab Med, 2018, 41: 615-620) Key words: Proteins; Luminescent measurements; Immunoassay; Ovarian neoplasms; Evaluation studies

The diagnostic value of human epididymis protein 4 as a novel biomarker in patients with renal dysfunction.

In this study, we investigated the diagnostic value of human epididymis protein 4 (HE4) in acute and chronic renal dysfunction and analyzed the correlation between HE4 levels and the results of routine renal function tests. We aimed to provide evidence to establish HE4 as a novel biomarker of renal injury and its appropriate application as a marker of ovarian cancer. We collected 259 serum samples from hospitalized patients with different causes of renal damage. HE4 serum levels were detected by chemiluminescence and the levels of serum creatinine, urea, and cystatin C were tested by conventional clinical chemical methods. The levels of HE4 were highest in the acute kidney injury groups and chronic kidney disease groups, although other groups were also significantly higher than the control group. HE4 and creatinine, urea, and cystatin C had a positive linear correlation. In contrast, HE4 and estimated glomerular filtration rate (eGFR) had a negative linear correlation, with a correlation coefficient of - 0.674 (P < 0.01). Area under the receiver-operating characteristic curve analysis showed that HE4 has higher diagnostic value compared with creatinine, urea, and cystatin C in both acute and chronic renal injury patients; however, HE4 and creatinine have a similar diagnostic value. Notably, HE4 concentration gradually increased with a decline of glomerular filtration rate, with significant differences evident between different eGFR stages. HE4 is a potential biomarker of kidney injury in acute and chronic renal dysfunction. Importantly, clinicians should be aware of this when using HE4 to diagnose ovarian cancer.

Serum human epididymis protein 4 is a predictor for developing nephritis in patients with systemic lupus erythematosus: A prospective cohort study

BackgroundIt has been demonstrated that serum human epididymis protein 4 (HE4) is a useful biomarker for differentiating lupus nephritis (LN) from systemic lupus erythematosus (SLE). However, it remains unclear whether HE4 can be used to predict the development of LN. MethodsA total of 74 SLE patients without LN were recruited between August 2008 and September 2013. Serum HE4 concentrations were measured by enzyme-linked immunosorbent assay. These patients were followed up from the date of SLE diagnosis to LN development or the end of the study. The receiver operating characteristics (ROC) curve was drawn to assess the predictive value of HE4 for the incidence of LN. In addition, Kaplan–Meier and Cox regression analyses were used to determine the prognostic factors for the incidence of LN. ResultsSerum HE4 levels significantly increased in patients who are positive for anti-dsDNA antibody, low C3 and the incidence LN (P < 0.05), and these were closely correlated with age, erythrocyte sedimentation rate (ESR) and the SLE disease activity index (SLEDAI) (P < 0.05). During the follow-up, 44 patients developed LN. The ROC curve revealed that for HE4 levels, the predictive performance for LN with 64.8 pM as an optimal cutoff yielded an AUC of 0.714, with a 95% confidence interval of 0.597–0.831, and a sensitivity and specificity of 81.8% and 53.3%, respectively. The Kaplan-Meier analysis revealed that LN occurred in 72% of high-HE4 patients and 33.3% of low-HE4 patients (P = 0.036). The univariate analysis revealed that anti-dsDNA antibody, low C3, SLEDAI and HE4 were significantly associated with the incidence of LN (P < 0.05). Multivariate Cox regression revealed that only SLEDAI and HE4 were independently associated with the incidence of LN. ConclusionElevated serum HE4 is significantly associated with a higher risk of incidence for LN, and may be a useful predictor for developing LN.

Measurement of HE4 and CA125 and establishment of reference intervals for the ROMA index in the sera of pregnant women.

Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are biomarkers for ovarian cancer. Their specificity and sensitivity are often limited during pregnancy as a result of great fluctuations. The risk of ovarian malignancy algorithm (ROMA) score, which combines CA125, HE4, and menopausal status, may improve diagnostic performance. There are no reports regarding the ROMA index in pregnant women. Therefore, the aim of our study was to establish appropriate reference intervals (RIs) for the ROMA index in pregnant Chinese women and compare them with those of CA125 and HE4 during pregnancy. Serum concentrations of CA125 and HE4 were simultaneously measured in healthy pregnant women via electrochemiluminescence immunoassay (ECLIA). The ROMA index was calculated using premenopausal algorithms. The RIs for the ROMA index calculated by premenopausal algorithms were substantially closer to the normal range in the first 2 trimesters. For pregnant women, the great misclassifications identified in CA125 may be reversed by the use of ROMA index. We established the RIs for HE4 and CA125, as well as the ROMA index, in pregnant women at different gestational periods. The ROMA index is suggested to be a more promising tumor marker for pregnant women diagnosed with malignance.

Molecularly Imprinted Photo-electrochemical Sensor for Human Epididymis Protein 4 Based on Polymerized Ionic Liquid Hydrogel and Gold Nanoparticle/ZnCdHgSe Quantum Dots Composite Film.

A novel ionic liquid, 3-{[{4-[((carbamoyl)amino)ethyl methacrylate]butyl} ((carbamoyl)amino)ethyl methacrylate]propyl}-1-ethenyl-1H-imidazol-3-ium bromide (CCPEimBr) functionalized with vinyl, amino, and methacrylate groups, was synthesized and characterized with 1H NMR, FTIR, and HPLC-MS techniques. CCPEimBr was adopted as the functional monomer to prepare a molecularly imprinted polymerized ionic liquid hydrogel film on a glassy carbon electrode surface for human epididymis protein 4 (HE4) sensing. Gold nanoparticles (AuNPs) and ZnCdHgSe QDs were incorporated into the imprinted film as photo-electric active materials. The photocurrent response was measured to investigate the sensing performance of the imprinted sensors toward HE4. The imprinted photo-electrochemical sensor shows excellent selectivity, sensitivity, stability, and accuracy for HE4 determination. Experimental conditions including incubation time and pH value for determining HE4 were optimized in this study. The photocurrent variation (ΔI) decreased with increasing HE4 concentration (cHE4), and it was linearly proportional to cHE4 varied from 25 pg mL-1 to 4.0 ng mL-1. The detection limit of the imprinted sensor for determining HE4 was estimated to be 15.4 pg mL-1 (S/N = 3). The imprinted photo-electrochemical sensor was used to determine HE4 in human serum samples accurately.

Human Epididymis Protein 4 as a Potential Biomarker of Chronic Kidney Disease in Female Patients With Normal Ovarian Function.

Elevated serum concentrations of human epididymis protein 4 (HE4) have appeared in a large number of female patients with chronic kidney disease (CKD). However, it is unknow whether HE4 could be a potential biomarker for diagnosis of CKD. To evaluate whether serum HE4 is a potential biomarker of CKD in our cohort of 238 ethnic Han Chinese female patients, between the ages of 19 and 89 years. We selected 230 healthy control individuals and 238 female patients with CKD for inclusion in our study. We acquired their demographic characteristics and evaluated their renal function by measuring serum creatinine, blood urea nitrogen, and uric acid levels. The serum concentrations of HE4 were quantified via chemiluminescence immunoassay. Serum HE4 levels were significantly higher in the patients with CKD compared with controls (P <.001). Meanwhile, HE4 levels showed significant differences among 5 CKD subgroups via multiple comparison (P <.05) and presented significantly better diagnostic value than other indicators. Also, the results of binary logistic regression analysis indicated that HE4 showed significant correlation with the prevalence of CKD (P <.001) and had a larger odds ratio (OR) value. HE4 can serve as a potential biomarker for prediction of CKD and has important reference value for CKD staging.

Performance of ROMA based on Architect CA 125 II and HE4 values in Chinese women presenting with a pelvic mass: A multicenter prospective study

BackgroundWe evaluated the performance of human epididymis protein 4 (HE4), cancer antigen 125(CA 125) and Risk of Ovarian Malignancy Algorithm (ROMA) in distinguishing between benign and malignant pelvic masses in Chinese women. MethodFrom April to December 2012, women with a pelvic mass scheduled to have surgery were enrolled in a prospective, multi-center study conducted in 5 different regions in China. Preoperative serum concentrations of HE4 and CA 125 were examined and ROMA was calculated. ResultsA total of 684 women with a pelvic mass were included, of which 482 were diagnosed with benign conditions and 202 were diagnosed with malignant ovarian tumors. At cutoffs of 7.4% and 25.3% for ROMA, the sensitivities and specificities were 85.6% and 81.7% for all patients, 85.7% and 81.5% for premenopausal women, and 85.6% and 83.9% for postmenopausal women, respectively. The ROC-AUC of ROMA was significantly better than that of HE4 (P=0.0003) or CA 125 (P<0.0001) for all malignant diseases (including EOC, Non-EOC, LMP, metastases and other pelvic malignancy with no involvement of the ovaries) compared with benign diseases for all patients. ConclusionsWe demonstrated the efficiency of ROMA in the distinction of ovarian cancers from benign disease in a multiple-regions Chinese population, especially in premenopausal women.