Are there relationship otosclerosis with serum HE4 and CA125 level? A pilot study.

BACKGROUND: HE4 and CA 125 are identified as a potential biomarker for the detection of some diseases with fibrosis. OBJECTIVES: The purpose of this pilot study was to evaluate the value of human epididymis protein 4 (HE4) and cancer antigen-125 (CA-125) in otosclerosis patients. MATERIAL AND METHODS: The study population consisted of 60 people (30 otosclerosis patients, 30 control group). We collected blood samples for HE4 and CA-125 levels. Serum HE4 and CA-125 levels were measured by enzyme-linked immunosorbent assay (ELISA). We compared the results between otosclerosis patients and the normal subject. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value. RESULTS: There was no differences in CA-125 level between the otosclerosis (20.3 U/mL [10.4-42.1] and control group (19.3 U/mL [15.3-49.8]) (p > 0.05). HE4 level was significantly higher in the otosclerosis group (60.9 pmol/L [32.1-101.8])] than the control group (25.3 pmol/L [12.4-91.9]) (p < 0.001). The AUC in ROC analysis of HE4 was 0.768 (p < 0.001). CONCLUSIONS AND SIGNIFICANCE: Serum HE4 level may be a useful biomarker in otosclerosis. Further studies with a larger number of patients are required to confirm our pilot results.

Urinary-based detection of MSL, HE4 and CA125 as an additional dimension for predictive and prognostic modelling in ovarian cancer.

Objectives: We have recently described a predictive/prognostic model for ovarian cancer, exploiting commonly available clinico-pathological parameters and the ovarian serum biomarkers mesothelin (MSL), human epididymis protein 4 (HE4) and cancer-antigen 125 (CA125). Considering urine as a prototype non-invasive sample, we investigated whether serum levels of these biomarkers are mirrored in urine and compared their clinical relevance in matched serum vs. urine samples. Methods: MSL, HE4 and CA125 were quantified in urinary (n=172) and matched serum samples (n=188) from ovarian cancer patients (n=192) using the Lumipulse® G chemiluminescent enzyme immunoassay (Fujirebio). Results: While absolute concentrations of MSL or CA125 were higher in serum than in matched urine samples, HE4 concentrations were considerably higher in urine than in serum. Nonetheless, the levels of all three biomarkers strongly correlated between matched serum vs. urine samples and were unrelated to BRCA1/2 mutational status. Consequently, prediction of surgical outcome or relapse/death by MSL, HE4 or CA125 was similarly efficient among urinary- vs. serum-based detection. HE4 provided the highest capacity to predict surgical outcome or relapse/death among both body fluids (urine: AUC=0.854; serum: AUC=0.750, respectively). All clinically relevant findings regarding the investigated urinary biomarkers were equally reproducible among raw vs. creatinine-normalized datasets, suggesting that normalization may have subordinate priority for urine-based analysis of these biomarkers. Conclusion: We report that the capacity of MSL, HE4 and CA125 to predict surgical outcome and relapse/death is equivalent between serum vs. urine-based detection. Urinary biomarkers, in particular HE4, may provide an additional dimension for prognostic modeling in ovarian cancer.

Diagnostic Utility of Selected Matrix Metalloproteinases (MMP-2, MMP-3, MMP-11, MMP-26), HE4, CA125 and ROMA Algorithm in Diagnosis of Ovarian Cancer.

Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.

HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation.

Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease. Identifying biomarkers for early diagnosis is of great clinical importance. The epididymis protein 4 (HE4) is important in the process of inflammation and fibrosis in the epididymis. Its prognostic value in IPF, however, has not been studied. The mRNA and protein levels of HE4 were used to determine the prognostic value in different patient cohorts. In this study, prognostic nomograms were generated based on the results of the cox regression analysis. We identified the HE4 protein level increased in IPF patients, but not the HE4 gene expression. The increased expression of HE4 correlated positively with a poor prognosis for patients with IPF. The HR and 95% CI were 2.62 (1.61-4.24) (p < 0.001) in the training set. We constructed a model based on the risk-score = 0.16222182 * HE4 + 0/0.37580659/1.05003609 (for GAP index 0-3/4-5/6-8) + (- 1.1183375). In both training and validation sets, high-risk patients had poor prognoses (HR: 3.49, 95%CI 2.10-5.80, p = 0.001) and higher likelihood of dying (HR: 6.00, 95%CI 2.04-17.67, p = 0.001). Analyses of calibration curves and decision curves suggest that the method is effective in predicting outcomes. Furthermore, a similar formulation was used in a protein-based model based on HE4 that also showed prognostic value when applied to IPF patients. Accordingly, HE4 is an independent poor prognosis factor, and it has the potential to predict IPF patient survival.

Demons-Meigs syndrome caused by a giant ovarian fibroma: A case report.

Demons-Meigs syndrome is a very rare entity. It combines a benign ovarian "fibroma-like" tumor with ascites and hydrothorax. The notion of benignancy is the key point. CA-125 levels are most of the time normal, but high levels can be observed in rare cases which makes it difficult to have a diagnostic. We present here the case of a 43-year-old female patient who presented with abdominopelvic pain. Imaging discovered a 30 cm large intraabdominal mass with ascites and bilateral pleural effusion. Surgical resection of the tumor was performed, and pathology identified an ovarian fibroma. No postintervention complications were observed, with resorption of the ascites and hydrothorax.

Human epididymis protein 4: Analysis of national health and nutrition examination survey data.

BACKGROUND: Human epididymis protein 4 (HE4) is a tumor marker overexpressed in ovarian cancer and is commonly utilized to aid with diagnosis of an adnexal mass. HE4 levels vary based on pregnancy, age, menopausal status, and tobacco use. OBJECTIVE(S): The objective of this study was to evaluate population-based data to examine factors that affect HE4 among adult women in the United States and stratify levels of HE4 by demographic and gynecologic factors. STUDY DESIGN: A retrospective analysis was conducted using data from 2,480 women aged 20 + who participated in the National Health and Nutrition Examination Survey (2001-2002). From these cross-sectional data, serum HE4 and cotinine, a marker of tobacco exposure, were combined with demographic and interview data. Estimated glomerular filtration rates (eGFR) were based on serum creatinine, age, sex, and race. Other variables of interest included menopausal status, pregnancy, and various gynecologic factors. Summary HE4 data are provided as geometric means with associated 95 % confidence intervals. RESULTS: HE4 levels were independently associated with age, renal function, and nicotine use, all p < 0.001. Pre-menopausal women with a history of endometriosis were found to have elevated HE4 levels compared to those without, p < 0.01; however, we found no such difference among post-menopausal women. Adjusting for age, no differences in HE4 were found based on race/ethnicity, p = 0.29. HE4 levels showed statistically significant associations with income level; however, these were small and clinically irrelevant. CONCLUSION: This study provides evaluation of HE4 levels among a data set representative of 98.5 million non-institutionalized women in the United States and gives insight into extraneous factors that may influence these levels.

Function of homocysteine and HE4 in endometrial carcinoma: verified by prospective experiment.

Background: Timely diagnosis is the key factor to improve the prognosis of endometrial carcinoma (EC). To date, no particularly good markers could significantly improve the detection rate of EC. This study aimed to assess the utility of serum markers homocysteine (Hcy), human epididymal protein 4 (HE4), cancer antigen 199 (CA199), cancer antigen 125 (CA125), fibrinogen (Fib), and D-dimer (D-D) for EC diagnosis, especially Hcy of which its role in EC has not been noticed. Methods: Pre-test and verification tests were performed. In Pre-test, the diagnostic value of the included markers was evaluated and the right marker was chosen to establish an efficient new risk index for screening EC. In verification tests, the applicability of the new risk index was tested. Several evaluation indices including receiver operating characteristic (ROC) curve, Youden Index, sensitivity (SN), and specificity (SP), were adopted to assess the diagnostic value of the included markers for EC. Results: Hcy may be useful in the diagnosis of EC. Its diagnostic value was not significantly lower than that of HE4. Based on the diagnostic value of Hcy and HE4, a new risk index was established, which demonstrated high value in EC diagnosis (ROC, 0.801), especially among young female patients (age ≤50 years, ROC, 0.871). Furthermore, the level of Hcy, but not HE4, was notably different in normal or benign endometrial lesions, atypical endometrial hyperplasia (AEH), and EC. Conclusions: The change of Hcy levels could be used to diagnose EC and when taken into consideration together with the detection of HE4, the diagnostic accuracy of EC is further improved.

Human Epididymis Protein 4 (HE4) and Cancer Antigen 125 (CA125) for Prediction of Optimal Primary Surgery in Non-Mucinous Epithelial Ovarian Cancer.

OBJECTIVE: To determine the relationship between pre-operative HE4 and CA125 levels in non-mucinous epithelial ovarian cancer cases (EOC) and outcomes of primary surgery for prediction of optimal surgery. METHODS: A retrospective study was performed on non-mucinous EOC who underwent primary surgery at King Chulalongkorn Memorial Hospital from 2016 to 2020. Demographic and clinical characters were collected. Histopathology and pre-operative tumor markers namely HE4 and CA125 were also recruited. Primary surgical outcomes were classified as optimal (OS) and suboptimal surgery (SS). RESULTS: One hundred and seventy patients were enrolled in the study. There were 130 and 40 cases in OS and SS, respectively. Average age and body mass index (BMI) of EOC were 54.2 years old and 23.1 Kg/m2, respectively. Both groups had comparable demographic characteristics. Two-thirds (103/170) and one-third (63/170) had early stage and clear cell histopathology, respectively. The median level of HE4 were 118.60 and 603.45 pmol/L in OS and SS, respectively. OS and SS had average CA125 at 146.95 and 814.70 U/L, respectively. The best cut-off point of HE4 and CA125 less than 170.95 pmol/L and 316.4 U/mL gave predicting OS with area under curve (AUC) at 0.78 and 0.75, respectively. HE4 and CA125 cut-off point had sensitivity, specificity, positive predict value (PPV) and negative predictive value (NPV) at percentage of 60.8/60.8, 87.5/82.5, 94.1/91.9 and 40.7/39.3, respectively. CONCLUSION: HE4 and CA125 of non-mucinous EOC among OS had significantly less than SS and could be the predicting of optimal surgery.

Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.

OBJECTIVES: To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. METHODS: This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. RESULTS: We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79). CONCLUSION: Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

Predicting epithelial ovarian cancer prognosis: correlation of posttreatment 18F-fluorodeoxyglucose positron emission tomography-computed tomography metabolic parameters, serum carbohydrate antigen, and human epididymis protein levels with overall survival.

Background: Identifying reliable prognostic indicators can aid in improving patient care. The aim of this study was to establish the association of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) whole-body metabolic parameters, serum carbohydrate antigen 125 (CA125), and human epididymis protein 4 (HE4) with overall survival (OS) in patients with epithelial ovarian cancer (EOC) after surgery combined with platinum-based chemotherapy. Methods: From May 2014 to May 2019, a total of 79 patients with EOC who underwent posttreatment 18F-FDG PET/CT in the First Affiliated Hospital of Chongqing Medical University were included. Clinical data and laboratory indicators were obtained. The whole-body maximum standardized uptake value (WBSUVmax), whole-body metabolic tumor volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) were measured and calculated on 18F-FDG PET/CT. The follow-up was conducted until February 2023, and the endpoint was death from any cause. Pearson correlation analysis, Kaplan-Meier, and Cox proportional regression were used in this study. Results: The PET-positive (PET-P) patients had significantly decreased OS based on either Kaplan-Meier survival analysis (P<0.001) or univariate Cox regression analysis [hazard ratio (HR) =40.177, 95% confidence interval (CI): 2.690-600.134; P=0.007]. "Ln" is a logarithmic transformation with a base of "e" (natural logarithm). LnWBMTV, lnWBTLG, and therapy after PET were independent predictors of OS in a cohort of 63 PET-P patients. The difference in OS between groups sorted by the median WBMTV (4.16; P<0.001) and WBTLG (14.71; P<0.001) was statistically significant. There were statistically significant differences in CA125 and HE4 levels between patients in the PET-P and PET-negative (PET-N) groups (P<0.001). In the PET-P patient cohort, serum HE4 levels were substantially correlated with WBMTV and WBTLG. Kaplan-Meier survival analysis suggested a reduction in OS after treatment in patients with EOC positive for CA125, HE4, and PET (P<0.001). Conclusions: Post-PET/CT treatment strategy, WBMTV, and WBTLG demonstrated significant prognostic utility in predicting posttreatment OS in patients with EOC. Patients who tested positive for both tumor markers CA125 and HE4 and had a positive PET scan demonstrated a significantly poorer prognosis in terms of posttreatment OS.

Possible role of HE4 level elevation in the pathogenesis of TH2-high asthma.

OBJECTIVES: As a heterogeneous disease, asthma is characterized by airway hyperresponsiveness, airway inflammation, and airway mucus hypersecretion. According to the pathological changes, symptoms, preventive and treatment methods, asthma can be divided into TH2-high and TH2-low asthma. We show that the expression of the tumor biomarker human epididymis protein 4 (HE4) was significantly increased in TH2-high asthma group, while there was no marked difference in its expression between TH2-low asthma and healthy control groups. HE4 levels were significantly increased in plasma, induced sputum, and alveolar lavage fluid (BALF) samples and airway epithelial cells from TH2-high asthma group, showing that HE4 has a possible role in the pathogenesis of TH2-high asthma. METHODS: Using RT-qPCR, ELISA, Western blot (WB), and immunohistochemistry, we assessed differences in HE4 expression in plasma, induced sputum, BALF, and airway epithelial cells among patients with the TH2-related asthma subtypes and healthy controls. To explore the role of HE4 in TH2-high asthma, we conducted a correlation analysis between HE4 levels in plasma, induced sputum, BALF, and airway epithelial cells and multiple indicators of airway eosinophilic inflammation, airway mucus secretion, and airway remodeling. CONCLUSION: We found for the first time that HE4 was differentially expressed in the TH2-related asthma subtypes. In TH2-high asthma, HE4 levels were markedly elevated in airway epithelial cells, plasma, induced sputum, and BALF. HE4 may play an important role in various pathogenic mechanisms of asthma, such as airway eosinophilic inflammation, airway mucus secretion, and airway remodeling. HE4 in plasma may be a clinically biomarker for differentiating TH2-related asthma subtypes.

Clinical Significance of the TK1-Specific Activity in the Early Detection of Ovarian Cancer.

INTRODUCTION: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer. METHODS: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples. RESULTS: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis. CONCLUSIONS: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.

A predictive and prognostic model for surgical outcome and prognosis in ovarian cancer computed by clinico-pathological and serological parameters (CA125, HE4, mesothelin).

OBJECTIVES: Numerous prognostic models have been proposed for ovarian cancer, extending from single serological factors to complex gene-expression signatures. Nonetheless, these models have not been routinely translated into clinical practice. We constructed a robust and readily calculable model for predicting surgical outcome and prognosis of ovarian cancer patients by exploiting commonly available clinico-pathological factors and three selected serum parameters. METHODS: Serum CA125, human epididymis protein 4 (HE4) and mesothelin (MSL) were quantified by Lumipulse® G chemiluminescent enzyme immunoassay (Fujirebio) in a total of 342 serum samples from 190 ovarian cancer patients, including 152 paired pre- and post-operative samples. RESULTS: Detection of pre-operative HE4 and CA125 was the optimal marker combination for blood-based prediction of surgical outcome (AUC=0.86). We constructed a prognostic model, computed by serum levels of pre-operative CA125, post-operative HE4, post-operative MSL and surgical outcome. Prognostic performance of our model was superior to any of these parameters alone and was independent from BRCA1/2 mutational status. We subsequently transformed our model into a prognostic risk index, stratifying patients as "lower risk" or "higher risk". In "higher risk" patients, relapse or death was predicted with an AUC of 0.89 and they had a significantly shorter progression free survival (HR: 9.74; 95 % CI: 5.95-15.93; p<0.0001) and overall survival (HR: 5.62; 95 % CI: 3.16-9.99; p<0.0001) compared to "lower risk" patients. CONCLUSIONS: We present a robust predictive/prognostic model for ovarian cancer, which could readily be implemented into routine diagnostics in order to identify ovarian cancer patients at high risk of recurrence.

Pre-analytical stability of the CEA, CYFRA 21.1, NSE, CA125 and HE4 tumor markers.

BACKGROUND: For lung cancer, circulating tumor markers (TM) are available to guide clinical treatment decisions. To ensure adequate accuracy, pre-analytical instabilities need to be known and addressed in the pre-analytical laboratory protocols. OBJECTIVE: This study investigates the pre-analytical stability of CA125, CEA, CYFRA 21.1, HE4 and NSE for the following pre-analytical variables and procedures; i) whole blood stability, ii) serum freeze-thaw cycles, iii) electric vibration mixing and iv) serum storage at different temperatures. METHODS: Left-over patient samples were used and for every investigated variable six patient samples were used and analysed in duplicate. Acceptance criteria were based on analytical performance specifications based on biological variation and significant differences with baseline. RESULTS: Whole blood was stable for at least 6 hours for all TM except for NSE. Two freeze-thaw cycles were acceptable for all TM except CYFRA 21.1. Electric vibration mixing was allowed for all TM except for CYFRA 21.1. Serum stability at 4°C was 7 days for CEA, CA125, CYFRA 21.1 and HE4 and 4 hours for NSE. CONCLUSIONS: Critical pre-analytical processing step conditions were identified that, if not taken into account, will result in reporting of erroneous TM results.

Silencing HE4 alleviates the renal fibrosis in lupus nephritis mice by regulating the C3/MMPs/prss axis.

To explore the regulatory effect of human epididymis protein 4 (HE4) on renal fibrosis in mice with lupus nephritis (LN) and the underlying mechanism. Ten-week old MRL/LPR mice were injected with HE4 shRNA adenovirus vector through the renal pelvis for 5 days. Renal tissues were extracted for HE and Masson staining to evaluate pathological changes and fibrosis in lupus nephritis mice. The level of urine protein was measured using a biochemical analyzer, while the expression level of HE4 and p-NF-κB p65 in renal tissues was visualized using an immunofluorescence assay. The level of ß2-microglobulin (ß2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (Kim-1) was determined by the immunohistochemical assay. Western blotting was used to determine the levels of C3, HE4, matrix metalloproteinase-2 (MMP2), MMP9, p-p65, prss23, and prss35 in renal tissues. Compared to wild-type C57BL/6 mice, MRL/LPR mice showed a marked increase in the number of glomeruli, hyperplasic basement membrane, severe infiltration of inflammatory cells in renal tubules and glomeruli, obvious necrosis in glomeruli, elevated fibrosis levels, and increased levels of urine protein, ß2-MG, NGAL, Kim-1, C3, HE4, MMP2, MMP9, and p-p65; and decreased levels of prss23 and prss35 were observed in MRL/LPR mice. After the administration of the HE4 shRNA adenovirus vector, the repaired structure of renal tubules and glomeruli improved infiltration of inflammatory cells, reduced collagen fiber and urine protein, suppressed levels of C3, HE4, MMP2, MMP9, and p-P65, and facilitated the expression of prss23 and prss35 which were observed. Silencing HE4 improved renal fibrosis and inhibited inflammation in mice with lupus nephritis, which may play a role in inhibiting C3/MMPs and promoting prss-related protein expression.

Response surface methodology, and artificial neural network model for removal of textile dye Reactive Yellow 105 from wastewater using Zeolitic Imidazolate-67 modified by Fe3O4 nanoparticles.

The applicability of Zeolitic Imidazolate-67, Modified by Fe3O4 Nanoparticles, was studied for removing textile dye Reactive yellow 105 from wastewater by adsorption method using response surface methodology (RSM). For the adsorption characterization of the adsorbent used in HE-4G dye adsorption, BET, FTIR, XRD, and SEM analyses were performed. The impacts of variables, including initial HE-4G dye concentration (X1), pH (X2), adsorbent dosage (X3), and sonication time (X4), the highest removal efficiency as 98%, 10 mg/L initial concentration, pH 6, 0.025 g adsorbent dosage, and 6.0 min time respectively. Adsorption equilibrium and kinetic data it, that data were for the Langmuir isotherm, pseudo-second-order kinetics, and maximum adsorption capacity (105.0 mg/g), respectively. Thermodynamic parameters indicated HE-4G dye adsorption is feasible, spontaneous and exothermic. Promising treatment capabilities of the ZIF-67-Fe3O4NPs have been during the comparative adsorption removal of HE-4G dye from DI water against spiked natural water samples and synthetic Na+, K+, Ca2+, and Mg2+ solutions. The observed outcome is the suitability of the artificial neural network model as a tool for mean square error, (MSEANN = 0.53, and R2 = 0.9926) for removing HE-4G dye. Results that ZIF-67-Fe3O4NPs, like being recyclable, and cost-efficient made it a promising absorbent for wastewater.

Recent Advances in Surface Plasmon Resonance (SPR) Technology for Detecting Ovarian Cancer Biomarkers.

Epithelial Ovarian Cancer (EOC) is a leading cause of cancer-related deaths among women, mainly due to a lack of early detection and screening methods. Advanced immunoassay techniques, such as Luminex and proximity extension assay (PEA) technology, show promise in improving EOC detection by utilizing highly sensitive and specific multiplex panels to detect multiple combinations of biomarkers. However, these advanced immunoassay techniques have certain limitations, especially in validating the performance characteristics such as specificity, sensitivity, limit of detection (LOD), and dynamic range for each EOC biomarker within the panel. Implementing multiplexing in point-of-care (POC) biosensors can enhance EOC biomarker detection, with Surface Plasmon Resonance (SPR) being a versatile option among optical biosensors. There is no study on multiplex SPR biosensors specifically tailored for diagnosing EOC. Recent studies have shown promising results in the single detection of EOC biomarkers using SPR, with LOD for cancer antigen 125 (CA125) at 0.01 U/mL-1 and human epididymis protein 4 (HE4) at 1pM. This study proposes a potential roadmap for scientists and engineers in academia and industry to develop a cost effective yet highly efficient SPR biosensor platform for detecting EOC.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.

BACKGROUND: Lung cancer is the most common cause of malignant pleural effusion (MPE). Serum human epididymis secretory protein 4 (HE4) is a useful diagnostic marker for lung cancer. OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of pleural fluid HE4 for MPE. DESIGN: A prospective, double-blind diagnostic test accuracy study. METHODS: Patients with undiagnosed pleural effusion were enrolled in two cohorts (Hohhot and Changshu). Electrochemiluminescence immunoassay was used to detect pleural fluid HE4. The diagnostic accuracy of HE4 was evaluated by a receiver operating characteristic (ROC) curve, and the net benefit of HE4 was assessed by a decision curve analysis (DCA). RESULTS: A total of 66 MPEs and 86 benign pleural effusions (BPEs) were enrolled in the Hohhot cohort. In the Changshu cohort, 26 MPEs and 32 BPEs were enrolled. In both cohorts, MPEs had significantly higher pleural fluid HE4 than BPEs. The area under the ROC curve (AUC) of HE4 was 0.73 (95% CI: 0.64-0.81) in the Hohhot cohort and 0.79 (95% CI: 0.67-0.91) in the Changshu cohort. At a threshold of 1300 pmol/L, HE4 had sensitivities of 0.44 (95% CI: 0.33-0.56) in the Hohhot cohort and 0.54 (95% CI: 0.35-0.73) in the Changshu cohort. The corresponding specificities were 0.90 (95% CI: 0.83-0.95) in the Hohhot cohort and 0.94 (95% CI: 0.84-1.00) in the Changshu cohort. In subgroup analyses, HE4 had an AUC (95% CI) of 0.78 (0.71-0.85) in exudates and an AUC of 0.69 (0.57-0.81) in patients with negative effusion cytology. The DCA revealed that HE4 determination had a net benefit in both cohorts. CONCLUSION: Pleural fluid HE4 has moderate diagnostic accuracy for MPE and has net benefit in pleural effusion patients with unknown etiology.

Combination of serum CST1 and HE4 for early diagnosis of endometrial cancer.

Purpose: Optimal serological biomarkers have been absent for the early diagnosis of endometrial cancer, to date. In this study, we aimed to define the diagnostic performances of individual and combined detection of serum cysteine protease inhibitor 1 (CST1) with traditional tumor markers, including glycated antigen 125 (CA125) and human epididymis protein 4 (HE4), in patients with early-stage endometrial cancer (EC). Methods: The performances of individual and combined detection of serum CST1, HE4, and CA125 were evaluated by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay, respectively. A training data set of 67 patients with early EC, 67 patients with endometrial benign lesion (EBL), and 67 healthy controls (HC) was used to develop a predictive model for early EC diagnosis, which was validated by an independent validation data set. Results: In the training data set, serum CST1 and HE4 levels in the early EC group were significantly higher than in EBL/HC groups (P < 0.05), while there was no significant difference of serum CA125 level between the early EC and EBL/HC groups (P > 0.05). Serum CST1 and HE4 exhibited areas under the curve (AUC) of 0.715 with 31.3% sensitivity at 90.3% specificity, and 0.706 with 23.9% sensitivity at 95.5% specificity, respectively. Combined detection of serum CST1 and HE4 exhibited an AUC of 0.788 with 49.3% sensitivity at 92.5% specificity. The combination of serum CST1 and HE4 showed promise in diagnosis. Conclusion: CST1 is a prospective serological biomarker for early EC diagnosis, and the combination of CST1 and HE4 contributes to the further improvement in the diagnosis of patients with early-stage EC.

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

BACKGROUND: We 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. METHODS: Ninety-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. RESULTS: Baseline 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. CONCLUSION: Elevated serum HE4 level at ICU admission highly correlates with COVID-19 severity and predicts disease outcome.