المؤلفون: Tang Y, Hu Z, Liu Z, Peng S, Liu T, Xiao Y, Peng J, Pan H, Zheng Z, He J

المصدر: International Journal of General Medicine, Vol Volume 17, Pp 1273-1280 (2024)

مصطلحات موضوعية: human epididymis protein 4, acute heart failure, chronic kidney disease, prognosis., Medicine (General), R5-920

الوصف: Yi Tang,1,* Zhengqi Hu,2,* Zhibin Liu,2 Siling Peng,2 Tiancheng Liu,2 Yaoyuan Xiao,2 Jianqiang Peng,1 Hongwei Pan,1 Zhaofen Zheng,1 Jin He1 1Department of Cardiology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Normal University, Changsha, People’s Republic of China; 2Department of Cardiology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jin He, Email 394929734@qq.comPurpose: The levels of human epididymis protein 4 (HE4) is associated not only with the prognosis of patients with acute heart failure (AHF), but also with chronic kidney disease (CKD). Our study aims to understand the prediction value of HE4 on prognosis in patients with AHF combined with CKD.Patients and Methods: This study prospectively enrolled patients diagnosed with AHF combined with CKD at the Department of Cardiology of Hunan Provincial People’s Hospital from March 2019 to December 2022. Serum levels of HE4 were measured using a chemiluminescence microparticle immunoassay. The endpoint events included heart failure readmission and cardiovascular death.Results: A total of 130 patients with AHF combined with CKD were included in the stud. The median age is 73 years (interquartile range: 65– 79 years). Among the patients, 94 experienced the endpoint events. The multivariable Cox analysis reveals that LnHE4 (HR=2.280, 95% CI 1.300– 3.998, P = 0.004) and age (HR=1.024, 95% CI 1.003– 1.045, P = 0.025) are independent predictors of the endpoint events. The Kaplan-Meier survival curve demonstrates that patients with HE4 levels> 276.15 pmol/L has a significantly higher incidence of endpoint events compared to those with HE4 levels≤ 276.15 pmol/L (Log rank test: χ 2=19.689, P < 0.001). After adjusting for age and gender, the HR is 2.520 (95% CI: 1.626– 3.906, P < 0.001).Conclusion: HE4 is an independent predictor of heart failure readmission and cardiovascular death in patients with AHF combined with CKD.Keywords: Human epididymis protein 4, Acute heart failure, Chronic kidney disease, Prognosis

وصف الملف: electronic resource

العلاقة: https://www.dovepress.com/he4-serum-levels-are-associated-with-poor-prognosis-in-patients-with-a-peer-reviewed-fulltext-article-IJGMTest; https://doaj.org/toc/1178-7074Test

الوصول الحر: https://doaj.org/article/2b7fc8d21aa947f0a4928c54b96dfb70Test

المؤلفون: Tingting Zhang, Lanhe Chu, Wenchong Tan, Cuiping Ye, Hangming Dong

المصدر: The Clinical Respiratory Journal, Vol 18, Iss 5, Pp n/a-n/a (2024)

مصطلحات موضوعية: diagnosis, human epididymis protein 4, lung adenocarcinoma, lung cancer, prognosis, Diseases of the respiratory system, RC705-779

الوصف: Abstract Objective This study aimed to explore the application value of human epididymis protein 4 (HE4) in diagnosing and monitoring the prognosis of lung cancer. Methods First, TCGA (The Cancer Genome Atlas) databases were used to analyze whey‐acidic‐protein 4‐disulfide bond core domain 2 (WFDC2) gene expression levels in lung cancer tissues. Then, a total of 160 individuals were enrolled, categorized into three groups: the lung cancer group (n = 80), the benign lesions group (n = 40), and the healthy controls group (n = 40). Serum HE4 levels and other biomarkers were quantified using an electro‐chemiluminescent immunoassay. Additionally, the expression of HE4 in tissues was analyzed through immunohistochemistry (IHC). In vitro cultures of human airway epithelial (human bronchial epithelial [HBE]) cells and various lung cancer cell lines (SPC/PC9/A594/H520) were utilized to detect HE4 levels via western blot (WB). Results Analysis of the TCGA and UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal) databases showed that WFDC2 gene expression levels were upregulated in lung cancer tissues (p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1752-6981Test; https://doaj.org/toc/1752-699XTest

الوصول الحر: https://doaj.org/article/5f33c40aa13940fbae6e6d592537f0d2Test

المؤلفون: Xiangyu Li, Kun Chen, Jie Li, Xuemei Tang, Haoyu Ruan, Ming Guan

المصدر: Frontiers in Immunology, Vol 15 (2024)

مصطلحات موضوعية: cerebrospinal fluid, human epididymis protein 4, CEACAM6, lung adenocarcinoma, leptomeningeal metastasis, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundThe diagnosis of lung adenocarcinoma (LUAD) leptomeningeal metastasis (LM) remains a clinical challenge. Human epididymis protein 4 (HE4) functions as a novel tumor biomarker for cancers. This study aimed to assess the diagnostic value of cerebrospinal fluid (CSF) HE4, and combined with CEACAM6, for LUAD LM.MethodsThe CSF HE4 protein level was measured in two independent cohorts by electrochemiluminescence. Test cohort included 58 LUAD LM patients, 22 LUAD patients without LM (Wiot-LM), and 68 normal controls. Validation cohort enrolled 50 LUAD LM patients and 40 normal controls, in parallel with Wiot-LM patients without brain metastases (19 Wiot-LM/BrM patients) or with BrM (26 BrM patients). The CSF level of CEA, CA125, CA153, CA199, CA724, NSE and ProGRP of these samples was measured by electrochemiluminescence, whereas the CSF CEACAM6 level was detected by enzyme-linked immunosorbent assay (ELISA). In addition, the serum level of these biomarkers was detected by same method as CSF.ResultsThe level of HE4 or CEACAM6 in CSF samples from LUAD LM patients was significantly higher than those from normal controls and Wiot-LM patients. The HE4 or CEACAM6 level in CSF was higher than that in serum of LM patient. The CSF HE4 or CEACAM6 level for distinguished LM from Wiot-LM showed good performance by receiver-operating characteristic analysis. The better discriminative power for LM was achieved when HE4 was combined with CEACAM6. In addition, the CSF HE4 and CEACAM6 level showed little or no difference between Wiot-LM/BrM and BrM patients, the BrM would not significantly influence the HE4 or CEACAM6 level in CSF. The diagnostic power of CSF CA125, CA153, CA199, CA724, NSE and ProGRP for LUAD LM were not ideal.ConclusionThe combination with HE4 and CEACAM6 has the promising application for the diagnosis of LUAD LM.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1339914/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/55c393ac19d545cca44f213e85f4bf3bTest

المؤلفون: Roberto Angioli, Marco Santonico, Giorgio Pennazza, Roberto Montera, Daniela Luvero, Alessandra Gatti, Alessandro Zompanti, Panaiotis Finamore, Raffaele Antonelli Incalzi

المصدر: Diagnostics, Vol 14, Iss 5, p 561 (2024)

مصطلحات موضوعية: ovarian cancer, sensor array, carbohydrate antigen 125, human epididymis protein 4, Medicine (General), R5-920

الوصف: 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.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2075-4418/14/5/561Test; https://doaj.org/toc/2075-4418Test

الوصول الحر: https://doaj.org/article/e564e2e6908f456683e4fef924ec4d7eTest

المؤلفون: Jinye Song, Ling Chen, Zheping Yuan, Xuezhong Gong

المصدر: Frontiers in Pharmacology, Vol 14 (2023)

مصطلحات موضوعية: human epididymis protein 4, N-terminal prohormone of B-type natriuretic peptide, acute kidney injury, chronic kidney disease, biomarkers, Therapeutics. Pharmacology, RM1-950

الوصف: 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 351.5 pmol/L, 274.5 pg/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.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2023.1269311/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/8621485092d6469ea52658cf109eb938Test

المؤلفون: Valerio Mais, Maria Luisa Fais, Michele Peiretti, Daniela Fanni, Elena Massa, Giulia Carboni, Giuseppina Fais, Giuseppe Deo, Stefano Angioni

المصدر: Current Oncology, Vol 29, Iss 11, Pp 8540-8555 (2022)

مصطلحات موضوعية: endometrial cancer, endometrial hyperplasia, cancer genome atlas, human epididymis protein 4, HE4, immunohistochemistry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Low-grade stage I endometrioid endometrial carcinomas should have an excellent prognosis, but a small subset of these cancers can relapse. The search for putative immunohistochemical prognostic markers for relapse in low-risk/low-grade endometrioid endometrial cancers remains open. Among the candidate molecules that may implicate the roles of immunohistochemical risk markers, we focused our attention on human epididymis protein 4 (HE4) after a review of the literature. Few authors have devoted themselves to this topic, and none have found a correlation between the tissue expression of HE4 and the molecular classification of endometrial cancer. Five different variants of HE4 mRNA and multiple protein isoforms of HE4 were identified many years ago, but current HE4 assays only measure the total HE4 expression and do not distinguish the different proteins encoded by different mRNA variants. It is important to have an approach to distinguish specific variants in the future.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1718-7729/29/11/673Test; https://doaj.org/toc/1198-0052Test; https://doaj.org/toc/1718-7729Test

الوصول الحر: https://doaj.org/article/0be9f66cde6d467eb6f660f8a201f386Test

المؤلفون: Vikneswary Ravi Kumar, Nirmala Chandralega Kampan, Nor Haslinda Abd Aziz, Chew Kah Teik, Mohamad Nasir Shafiee, P. Susthitha Menon

المصدر: Cancers, Vol 15, Iss 23, p 5607 (2023)

مصطلحات موضوعية: epithelial ovarian cancer (EOC), biomarkers, cancer antigen 125 (CA125), human epididymis protein 4 (HE4), immunoassay, multiplex, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: 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.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/15/23/5607Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/7bf95d6955924a20847f020e0548b07fTest

المؤلفون: Yuan Zhan, Jinkun Chen, Jixing Wu, Yiya Gu, Qian Huang, Zhesong Deng, Shanshan Chen, Xiaojie Wu, Yongman Lv, Zhilin Zeng, Jungang Xie

المصدر: Respiratory Research, Vol 23, Iss 1, Pp 1-14 (2022)

مصطلحات موضوعية: Human epididymis protein 4, Airway epithelium inflammation, Fibroblast differentiation and proliferation, Chronic obstructive pulmonary disease, Diseases of the respiratory system, RC705-779

الوصف: Abstract Background Chronic obstructive pulmonary disease (COPD) is a progressive disease characterized by chronic inflammation and airway remodeling. Human epididymis protein 4 (HE4) plays a critical role in various inflammatory or fibrotic diseases. However, the role of HE4 in COPD remains unidentified. Methods HE4 expression was determined in the lung tissues from COPD patients and cigarette smoke (CS)-exposed mice using immunohistochemical staining, qPCR, or western blot. The plasma level of HE4 was detected by ELISA. The regulations of HE4 in the expressions of CS extract (CSE)-induced inflammatory cytokines in human bronchial epithelial cells (HBE) were investigated through knockdown or overexpression of HE4. The role of secretory HE4 (sHE4) in the differentiation and proliferation in human pulmonary fibroblast cells (HPF) was explored via qPCR, western blot, CCK8 assay or 5-ethynyl-2′-deoxyuridine (EdU) staining. The probe of related mechanism in CSE-induced HE4 increase in HBE was conducted by administrating N-acetylcysteine (NAC). Results HE4 was up-regulated in both the lung tissue and plasma of COPD patients relative to controls, and the plasma HE4 was negatively associated with lung function in COPD patients. The same enhanced HE4 expression was verified in CS-exposed mice and CSE-induced HBE, but CSE failed to increase HE4 expression in HPF. In vitro experiments showed that reducing HE4 expression in HBE alleviated CSE-induced IL-6 release while overexpressing HE4 facilitated IL-6 expression, mechanistically through affecting phosphorylation of NFκB-p65, whereas intervening HE4 expression had no distinctive influence on IL-8 secretion. Furthermore, we confirmed that sHE4 promoted fibroblast-myofibroblast transition, as indicated by promoting the expression of fibronectin, collagen I and α-SMA via phosphorylation of Smad2. EdU staining and CCK-8 assay demonstrated the pro-proliferative role of sHE4 in HPF, which was further confirmed by enhanced expression of survivin and PCNA. Pretreatment of NAC in CSE or H2O2-induced HBE mitigated HE4 expression. Conclusions Our study indicates that HE4 may participate in airway inflammation and remodeling of COPD. Cigarette smoke enhances HE4 expression and secretion in bronchial epithelium mediated by oxidative stress. Increased HE4 promotes IL-6 release in HBE via phosphorylation of NFκB-p65, and sHE4 promotes fibroblastic differentiation and proliferation.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1465-993XTest

الوصول الحر: https://doaj.org/article/6af0efc99a144f9dbf4dd98c6fd1aeaaTest

المؤلفون: Ankita Sethi, Lalit Kumar, Sandeep Mathur, Reeta Mahey, Garima Kachhawa, Neerja Bhatla

المصدر: South Asian Journal of Cancer, Vol 11, Iss 02, Pp 125-132 (2022)

مصطلحات موضوعية: ca-125, he4 tissue expression, human epididymis protein 4, immunohistochemistry, prognostic marker, serous epithelial ovarian cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Neerja Bhatla Background Human Epididymis protein 4 (HE4) is expressed in ovarian cancer. Preoperative serum testing is still not widely available. This pilot study aimed to investigate the magnitude of expression of HE4 in tissue sections of serous epithelial ovarian carcinoma, its correlation with clinical outcome, and the feasibility of HE4 immunohistochemistry as a prognostic marker. Materials and Method In this ambispective study, immunohistochemistry (IHC) was used to evaluate tissue sections of ovarian serous epithelial carcinoma at primary cytoreductive surgery. On HE4 immunohistochemistry (IHC), the magnitude of HE4 expression was assessed categorically as high or low HE4 expression and semiquantitatively by the H-score, and correlated with clinical outcome in terms of survival status, progression-free survival, and overall survival. Results Of 32 cases, most (n = 31, 96.8%) were positive for HE4 IHC. The mean age was 49 ± 8.2 years; 29 (90.6%) patients were in FIGO stage IIIC; 25 (78.9%) had ≥1cm residual disease after surgery; 31 (96.8%) received adjuvant chemotherapy, either 3-weekly (n = 25, 81.2%) or dose-dense weekly (n = 6, 18.8%) regimen. The majority (n = 31, 96.8%) had a high-grade tumor, of whom 19 (59.4%) had high HE4 expression and 13(40.6%) patients had H-score in the range of 5 to 8. The mean H-score was 6.97 ± 3.61 (range 0 to 12). The overall survival of the study population at 64 months was 36.65% (95% CI: 8.59–66.34), with median overall survival of 59 months. A new scoring system was developed combining categorical HE4 expression and serum CA-125 levels; the combination of HE4 expression with postoperative CA-125 levels was found to be the best prognostic marker for overall survival (p = 0.05). A composite score of 2 identified patients with poor progression-free survival (HR 4.64, p = 0.039) and overall survival (HR 5.45, p = 0.05). Conclusion The new composite scoring system using HE4 IHC with postoperative serum CA-125 levels offers an extremely useful option for prognosticating patients with serous epithelial ovarian carcinoma than serum CA-125 alone. This is useful where preoperative records are not available to the treating clinician.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2278-330XTest; https://doaj.org/toc/2278-4306Test

الوصول الحر: https://doaj.org/article/a95877937706450c8570bd7375d38c2aTest

المؤلفون: Harshita Dubey, Amar Ranjan, Julieana Durai, M.A. Khan, R. Lakshmy, Sachin Khurana, Swati Gupta, Jyoti Meena, M.D. Ray, Pranay Tanwar, Anita Chopra, Sanat Tiwari

المصدر: Cancer Treatment and Research Communications, Vol 34, Iss , Pp 100672- (2023)

مصطلحات موضوعية: Human epididymis protein 4, Uterine cervical cancer, Prognostic biomarker, Diagnostic biomarker, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Introduction: Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. Method: Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. Result: Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2468294222001630Test; https://doaj.org/toc/2468-2942Test

الوصول الحر: https://doaj.org/article/0de53e79c8c34dbc89dad253c01cf9f8Test