Human Epididymis Protein Research Articles

A clinical study of serum human epididymis protein 4 (HE4) in the diagnosis of pancreatic cancer.

Pancreatic cancer (PC) has poor early diagnosis rates due to its insidious onset. Since human epididymis protein 4 (HE4) is highly expressed in patients with PC, we assessed whether serum HE4 could be a marker for the detection 3 of PC. : Between May 2017 and October 2018, 127 patients with PC were recruited for the study along with 108 healthy controls who underwent health examinations. Serum HE4 concentrations were determined together with levels of carcinoembryonic antigen (CEA) and carbohydrate antigens (CA) 242 (CA242), CA19-9, CA15-3, and CA72-4 by electrochemiluminescence immunoassay (ECLIA) or chemiluminescence immunoassay (CLIA). Correlations between these biomarkers were assessed. : Serum levels of all six biomarkers were higher in patients with PC than in controls (P < 0.05). No correlation was observed between the serum levels of HE4 and the five other tumor markers, although there were strongly significant positive correlations between CA19-9 and CA15-3, and between CA242 and CA72-4. The lack of correlation indicates that HE4 has independent value in the diagnosis of PC. The combined assessment of serum HE4 levels and the other tumor markers improved the sensitivity of diagnosis. In particular, HE4 combined with CA19-9 performed significantly better than HE4 alone, or CA19-9 combined with the other markers. The HE4/CA19-9 combination resulted in 94.49% sensitivity and 99.07% specificity (95% confidence interval: 96.9-100). : HE4 is a biomarker associated with PC with a high specificity , either used alone, or evaluated with other biomarkers together improving the detection of PC. This study may provide a new clinical diagnostic approach for PC detection.

New insights into the diagnostic characteristics and clinical application of serum biomarkers for lung cancer, and human epididymis protein 4 as a new biomarker?

The value of serum tumor biomarkers used for lung cancer diagnosis is still controversial in clinical practice. This study aimed to further dissect and evaluate the clinical value of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1) together with a potential new biomarker, the human epididymis protein 4 (HE4) for lung cancer diagnosis, in a large cohort of a Chinese population. Ostensibly healthy individuals, as well as those with benign non-cancerous diseases, benign tumors, lung cancers, and other types of malignancies, were enrolled in the study. Serum ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were analyzed using the chemiluminescence immunoassay. Data were analyzed utilizing the SPSS and GraphPad Prism software. Detailed dissection of the diagnostic characteristics of serum 6 biomarkers on lung cancer was performed. All 6 biomarkers showed capabilities in characterizing lung cancer from other diseases. ProGRP and NSE were highly specific to small cell lung cancer (SCLC); SCC-Ag was a fair biomarker for NSCLC, specifically SCC histotype; CEA showed specificity to SCLC, followed by NSCLC; CYFRA21-1 was a good biomarker for both SCLC and NSCLC; HE4 showed high specificity to SCLC. For NSCLC characterization, CYFRA21-1+HE4+CEA was the best combinatory pattern in the terms of diagnostic performance (AUC=0.8110). The best combinatory analysis for SCLC was ProGRP+NSE+HE4 (AUC=0.9282). Patients with advanced stage, larger tumor, males, and age 50 or older had higher serum biomarkers levels than those with early stage, smaller tumor, females, and age under 50. Six biomarkers had capabilities in characterizing lung cancer with high or fair diagnostic performance. HE4 is a potential biomarker for both SCLC and NSCLC diagnosis, which merits further investigation.

Cardiac fibrosis and atrial fibrillation

Abstract Cardiac fibrosis is characterized by the imbalance of production and degradation of the extracellular matrix. The result of this process is an accumulation of scar tissue, which is associated with many pathological processes such as excessive mechanical stress on the heart, inflammation, ischemia, oxidative stress, or excessive neurohormonal activation. Fibrotic response results in damaged heart architecture and dysfunction of the heart. Cardiac fibrosis leads to increased stiffness of the left ventricle and arteries, promotes disorders of contraction and relaxation of the heart, disrupts electrophysiology of heart cells, and induces arrhythmias. Atrial fibrillation is one of the most common arrhythmias. It is associated with a deterioration in the quality of life and more frequent use of medical assistance. It is also an instantaneous risk factor for many diseases, including stroke. The underlying cause of this arrhythmia is electrical and structural remodeling induced by cardiac fibrosis. Therefore, much attention is paid to the search for biochemical markers that would allow non-invasive determination of the degree of this fibrosis. The promising markers include galectin-3, human epididymis protein 4 (HE4), serum soluble ST2, and adipose triglyceride lipase (ATGL). Studies have shown that plasma concentrations of these substances reflect the degree of myocardial fibrosis and are indirectly associated with AF. There are high hopes for the use of these markers in patients undergoing arrhythmia ablation. More research is needed to confirm that these markers can be used to estimate the chance of maintaining sinus rhythm in patients after ablation.

Prognostic Value of Human Epididymis Protein 4 in Connective Tissue Disease-Associated Interstitial Lung Disease with a Usual Interstitial Pneumonia Phenotype

Prognostic Value of Human Epididymis Protein 4 in Connective Tissue Disease-Associated Interstitial Lung Disease with a Usual Interstitial Pneumonia Phenotype

Human epididymis protein 4 as a new diagnostic biomarker for rheumatoid arthritis-associated interstitial lung disease

This study aimed to evaluate the role of human epididymis protein 4 (HE4) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. HE4 levels in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) samples were determined via electrochemiluminescence immunoassays in 102 RA patients (46 patients with ILD and 56 patients without ILD) and 51 healthy controls (HCs). Serum HE4 levels were significantly higher in RA-ILD patients (141.8±65.92 pmol/l) than those in the RA-no ILD patients (82.67±26.17 pmol/l) and healthy controls (35.72±7.6 pmol/l) (p<0.0001). Consistent with serum HE4 levels, BALF HE4 levels were significantly higher in RA-ILD patients (637.6±154.9 pmol/l) than those in the RA-no ILD patients (427.3±111.2 pmol/l) and healthy controls (206.9±30.46 pmol/l) (p<0.0001). In RA-ILD patients, HE4 levels were positively correlated with HRCT (high-resolution computed tomography) fibrosis scores, whereas a significant inverse relationship was found between HE4 levels and lung function parameters (such as, diffusion capacity of the lung for carbon monoxide (DLCO)). The logistic regression analysis showed that high levels of BALF HE4 (≥595 pmol/l) were associated with RA-ILD (odds ratio [OR] =8.09; 95% confidence interval [CI] =1.317-49.682; p=0.024). Serum and BALF HE4 levels were elevated in RA-ILD patients and strongly associated with the severity of ILD, thus supporting their potential clinical value as a new diagnostic aid for patients with RA-ILD.

Effect of Combination of Traditional Chinese Medicine with Western Medicine on Endometrial Carcinoma and Its Influence on Ultrasound, MRI, Tumor Markers HE4 and CA125.

Objective To study the clinical efficacy of integrated traditional Chinese medicine (TCM) and Western medicine (WM) in treating endometrial cancer and the influence on ultrasound, magnetic resonance imaging (MRI), tumor markers, human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125). Method A total of 152 cases of patients with endometrial carcinoma were randomly divided into two groups: the TCM + WM group and the WM group. The WM group was treated with megestrol acetate tablets, and the TCM + WM group was treated with Radix Astragali injection on the basis of the control group. The levels of inflammatory factors, HE4 and CA125 in serum, were detected using enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay. The characteristics of ultrasound images and MRI images were observed and recorded. Toxicity, side effects, and the 3-year cumulative survival rate after treatment were assessed. Results After treatment, the levels of interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in both groups decreased, and the decrease in the TCM + WM group was more obvious than that in the WM group. There were statistically significant differences between the two groups in lesion shape, boundary, blood flow signal, lesion diameter, resistance index (RI), echo, intima thickness, and muscle layer infiltration from transvaginal ultrasound images after treatment. The diameter, echo, boundary, shape, composition, and enhancement degree of lesions between the two groups have a significant difference. Moreover, the levels of serum HE4 and CA125 in both groups decreased after treatment, and the decrease in the TCM + WM group was more obvious than that in the WM group. There were statistically significant differences between the two groups in the occurrence of myelosuppression, abnormal liver function, decreased platelet number, gastrointestinal reactions, leukopenia, and cardiotoxicity. After three years of follow-up, the cumulative survival rate of the TCM + WM group was 76.32%, and the cumulative survival rate of the WM group was 57.89%. Conclusion Radix Astragali injection combined with megestrol acetate tablets has obvious therapeutic effects against endometrial cancer. Through vaginal ultrasonography and MRI, it can significantly improve the size, shape, and blood flow signals of patients' lesions, reduce the level of serum inflammatory factors and tumor markers HE4 and CA125, reduce the incidence of toxic and side reactions, improve the patient's immunity, improve the patient's condition significantly, and prolong the survival time of patients.

The predictive and prognostic value of CA 125 in endometrial cancer

Endometrial cancer is the most common malignant tumour of the female genital tract. It affects mainly older women, with postmenopausal bleeding as the primary symptom. The diagnosis of endometrial cancer is confirmed by histological evaluation of tissue specimens and described as either type I or type II. Treatment includes surgery (hysterectomy, adnexectomy and dissection of pelvic and paraaortic lymph nodes), radiotherapy, chemotherapy and hormonal therapy. Preoperative serum CA 125 (Cancer Antigen 125 or Carbohydrate Antigen 125) concentrations are correlated with depth of myometrial invasion, lymph node metastases, positive peritoneal cytology and invasion of the lymphovascular space, and can assist in making decisions about the extent of surgery. Preoperative CA 125 levels have prognostic value; postoperative levels serve as a predictor of early recurrence. Elevated serum CA 125 is linked not only with endometrial cancer, but also with several benign and malignant conditions, including ovarian cancer. Other tumour markers (e.g., CA 15–3, CA 19–9) and a promising new marker human epididymis protein 4 (HE4) can also be used for managing patients with endometrial cancer.

A Potential Serum Biomarker for Screening Lung Cancer Risk in High Level Environmental Radon Areas: A Pilot Study

Radon is a major cause of lung cancer (LC) deaths among non-smokers worldwide. However, no serum biomarker for screening of LC risk in high residential radon (HRR) areas is available. Therefore, the aim of this study was to determine diagnostic values of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (Cyfra21-1), human epididymis protein 4 (HE4), interleukin 8 (IL-8), migration inhibitory factor (MIF), tumor nuclear factor-alpha (TNF-α) and vascular endothelial growth factors (VEGF) occurring in high radon areas. Seventy-five LC non-smoker patients and seventy-five healthy controls (HC) were enrolled in this study. Among the HC groups, twenty-five HC were low residential radon (LRR) and fifty HC were HRR. Significantly higher (p < 0.0004) serum levels of CEA, Cyfra21-1, IL-8 and VEGF were found in the LC compared with the LRR and HRR groups. More importantly, significantly higher levels (p < 0.009) of serum CEA, Cyfra21-1 and IL-8 were observed in HRR compared with the LRR group. Likewise, a ROC curve demonstrated that serum CEA and Cyfra21-1 could better distinguish LC risk from HRR groups than IL-8. These results indicated that serum CEA and Cyfra21-1 were significantly increased in the HRR group and may be considered as potential biomarkers for individuals at high-risk to develop LC.

Diagnostic Value of Serum Markers Combined with TVCDS in Ovarian Cancer Patients Treated with Bushen Yiqi Quyu Prescription.

Background To compare the diagnostic value of serum markers human epididymal protein 4 (HE4) and cyclooxygenase-1 (COX-1) combined with transvaginal color Doppler sonography (TVCDS) in ovarian cancer (OC) treated with Bushen Yiqi Quyu prescription. Methods A total of 232 OC patients treated at the hospital from January 2018 to October 2020 were randomly divided into an observation group (n = 116) and control group (n = 116). The control group was treated with essential Western medication, and the observation group was treated with essential Western medication and Bushen Yiqi Quyu prescription. The clinical efficacy of the two groups was compared. The levels of HE4 and COX-1 were compared between the two groups before and after treatment. The ultrasonic features of TVCDS were compared between the two groups before and after treatment. The ROC curve was drawn to compare the sensitivity, specificity, and accuracy of single and combined detection of HE4, COX-1, and TVCDS in the observation group. Results The total effective rate of the observation group was significantly higher than that of the control group. After treatment, HE4 and COX-1 levels in both groups were considerably lower than those before treatment, and in the observation group, they decreased significantly than in the control group. HE4 and COX-1 were positively correlated with the clinical stage of OC. The higher the clinical stage, the higher the levels of HE4 and COX-1. After treatment, there was no significant difference in tumor location and the boundary between the two groups. There were statistically significant differences in tumor echo, nature, morphology, calcification, internal blood flow, and lymph node metastasis, and the difference in the observation group was more evident than in control group. The sensitivity, specificity, accuracy, positive detection rate, and negative detection rate of combined detection were higher than those of single detection. Conclusions Bushen Yiqi Quyu prescription has certain curative effects in the treatment of OC patients, which can significantly reduce the level of tumor markers and improve the symptoms of OC patients. The combined detection of HE4, COX-1, and TVCDS has high sensitivity, specificity, and accuracy, which can effectively detect OC and reduce missed diagnosis and misdiagnosis.

Human Epididymis Protein4 and Lewisy Enhance Chemotherapeutic Resistance in Epithelial Ovarian Cancer Through the p38MAPK Pathway.

Ovarian cancer has a high mortality rate due to difficulties in early detection and chemotherapy resistance. Human epididymal protein4 (HE4) has been adopted as a novel serum biomarker for early ovarian cancer diagnosis, and the presence of Lewisy antigen modifications on HE4 in ovarian cancer cell lines has been detected in previous studies. The aim of this study was to analyze the expression of HE4 and Lewisy antigen in human ovarian cancer in order to find a correlation between them, as well as with the clinical pathological parameters of patients with ovarian cancer. Immunohistochemistry was used to detect the respective expression of these compounds in two patient groups (chemotherapy-resistant and chemotherapy-sensitive) containing a total of 95 patients. Then, a bioinformatic approach was adopted and online large sample databases (TCGA, CCLE, and GTEx; Metascape, Cytoscape) were used to explore the potential mechanisms of action of these compounds. The results of this study demonstrate that high HE4 and Lewisy expression could be used as markers for chemotherapy resistance and poor prognosis in patients with ovarian cancer. These two expression events were widely correlated in various cancer tissues and are thought to act by activating the p38 mitogen-activated protein kinases (MAPK) pathway and inducing Vascular Endothelial Growth Factor A (VEGFA), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Early Growth Response 1 (EGR1), and Hypoxia-Inducible Factor 1-Alpha (HIFI1A), thereby promoting malignant biological behavior and resistance in ovarian cancer. These findings not only reveal the possible mechanism by which HE4 and Lewisy antigen affect ovarian cancer but also identify a four-gene signature that could be very useful in ovarian cancer detection and/or the development of new targeted therapies.

Serum HE4 and CA125 combined to predict and monitor recurrence of type II endometrial carcinoma

There is no recognized serum biomarker to predict the recurrence of endometrial carcinoma (EC). We aimed to explore serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) as the biomarkers to predict and monitor recurrence of type II EC. 191 patients diagnosed with type II EC were involved for this retrospective study. Comparing recurrent with non-recurrent patients, HE4 levels resulted a statistically significant difference at primary diagnosis and recurrence, respectively (P = 0.002 and P = < 0.001), while CA125 levels resulted statistically significant (P = < 0.001) at recurrence. According to receiver operating characteristic curve analysis, the areas under the curve were significant for HE4 levels at primary diagnosis and recurrence predicting recurrence. Furthermore, CA125 levels at recurrence were significant. And the combination of both markers showed the higher sensitivity and specificity than single one. Patients with higher HE4 levels were associated with worse disease-free survival and overall survival, the opposite was true for patients with lower HE4 levels. The preoperative HE4 levels could be used to evaluate the risk factors of type II EC. Which suggested that HE4 levels might associated with the prognosis of type II EC. And combination of HE4 and CA125 could be applied to monitor recurrence during follow-up.

Modified HE4, CA125, and ROMA cut-off values and predicted probability of ovarian tumor in Chinese patients.

Most prior studies investigating the risk of ovarian malignancy algorithm (ROMA) with cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) have involved Caucasian population or other populations. To date, there have been no unique calculations of predicted probability (PP) risk specifically for Chinese populations to help physicians in primary care settings. A group of 534 women with ovarian tumor diagnoses were enrolled and serum HE4 and CA125 were measured in each individual. Modified cut-off values were obtained by maximizing area under the curve (AUC) values and adjusted by using logistic regression with corresponding sensitivity (SN), specificity (SP), Youden index (YI), positive predictive value (PPV), and negative predictive value (NPV). By utilizing the ideal PPV, NPV, and AUC values, in premenopausal women modified HE4, CA125, ROMA, and PP cut-off values were 73.87 pmol/L, 61.60 U/mL, 18.47%, and 0.168, respectively. The same test values for postmenopausal women were 120.90 pmol/L, 76.21 U/mL, 26.48%, and 0.485, respectively. The SN for HE4 with the modified cut-off value was significantly lower than that for CA125 (P=0.040) in premenopausal women and lower than that for ROMA (P=0.001) and PP (P=0.044) in postmenopausal women. The AUC values for CA125, ROMA, and PP were all significantly higher than that for HE4 (P=0.006, 0.007, and 0.002, respectively) in postmenopausal women. The modified cut-off values for HE4, CA125, ROMA, and PP with ideal SN, SP, YI, NPV, PPV were useful of ruling out ovarian malignancy among both pre- and post-menopausal women. In premenopausal women modified HE4, CA125, ROMA, and PP cut-off values were 73.87 pmol/L, 61.60 U/mL, 18.47%, and 0.168, respectively and in postmenopausal women were 120.90 pmol/L, 76.21 U/mL, 26.48%, and 0.485, respectively.

Therapeutic Decision on Adnexal Masses: A Performance Protocol Based on HE4 Tumor Marker (Human Epididymis Protein 4), GI-RADS (Gynecology Imaging Reporting and Data System) and Hormonal Status

Therapeutic Decision on Adnexal Masses: A Performance Protocol Based on HE4 Tumor Marker (Human Epididymis Protein 4), GI-RADS (Gynecology Imaging Reporting and Data System) and Hormonal Status

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

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

Application and clinical significance of TCGA molecular classification in endometrial cancer

Objective: To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC). Methods: Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People's Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed. Results: (1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H (P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences (P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference (P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion: TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.

Human epididymis protein 4: a novel predictor of ischemic cardiomyopathy

BackgroundThe prognostic value of human epididymis protein 4 (HE4) in patients with ischemic cardiomyopathy (ICM) is unknown.MethodsA total of 103 patients with ICM were prospectively enrolled in this study from Hunan Provincial People’s Hospital between February 2019 and June 2019. All patients were tested for HE4 levels at baseline and follow-up. Endpoints of the study included cardiovascular death and heart failure-related hospitalization.ResultsA total of 96 patients with ICM were included for analysis. After a mean follow-up period of 263 (153–313) days, cardiovascular events were observed in 45 patients. Serum HE4 levels in patients with events were significantly higher than those in patients without events [188.70 (113.35–326.82) pmol/L versus 92.90 (61.50–123.20) pmol/L, P < 0.001]. Multivariate Cox regression analysis revealed that HE4 [χ2: 9.602, hazard ratio (HR): 1.003, 95% confidence interval (CI): 1.001–1.005, P = 0.002] and age [χ2: 4.55, HR: 1.044, 95% CI: 1.003–1.085, P = 0.033] were independent predictors of events. After adjusting for age and sex, the risk of events in patients with HE4 > 100.2 pmol/L was higher than that in patients with HE4 ≤ 100.2 pmol/L [HR: 3.372, 95% CI: 1.409–8.065, P < 0.001].ConclusionHE4 is an independent predictor of cardiovascular death and heart failure-related rehospitalization in patients with ICM.

Fluorescence turn-on immunosensing of HE4 biomarker and ovarian cancer cells based on target-triggered metal-enhanced fluorescence of carbon dots

Rapid and sensitive detection of tumor biomarkers and cancer cells is of crucial importance for the early diagnosis and prognosis prediction of cancer. The present report describes a target-induced fluorescence enhancement immunosensor that utilizes the optical property of carbon dots (CDs) and the metal-enhanced fluorescence effect (MEF) property of silver nanoparticles (AgNPs) for the sensitive detection of the cancer biomarker human epididymis protein 4 (HE4) and ovarian cancer cells. Nitrogen and sulfur co-doped CDs with a quantum yield of 85.6% were prepared and served as the fluorophore in MEF. The HE4 antibody (Ab) specific to the HE4 antigen was linked covalently to the surface of the synthesized CDs as the capture. The HE4 Ab-conjugated AgNPs (AgNPs-Ab) were prepared and utilized as signal amplification elements. In the presence of the target HE4, composite sandwich structures were formed between the labeled CDs-Ab and AgNPs-Ab, which brought the CDs and AgNPs into proximity, resulting in the fluorescence of CDs enhancement owing to MEF. The intensity of fluorescence enhancement was positively correlated with the HE4 concentration in the clinically important range of 0.01–200 nM with a limit detection of 2.3 pM. Moreover, the immunosensor was also successfully applied to specific fluorescence labeling and quantitative determination of HE4-positive ovarian cancer cells. The proposed target-triggered MEF sensor platform demonstrated high sensitivity, excellent anti-interference ability, along with successful validation in complex biological matrices, providing a new approach for HE4 detection in early diagnosis and therapeutic monitoring.

Role of Human Epididymis Protein 4 for Detection of Ovarian Carcinoma in Adnexal Masses

Role of Human Epididymis Protein 4 for Detection of Ovarian Carcinoma in Adnexal Masses

Past, Present, and Future of Serum Tumor Markers in Management of Ovarian Cancer: A Guide for the Radiologist.

The ability to accurately detect early ovarian cancer and subsequently monitor treatment response is essential to improving survival for patients with ovarian malignancies. Several serum tumor markers (STMs)-including cancer antigen 125 (CA-125), human epididymis protein 4 (HE4), cancer antigen 19-9 (CA 19-9), and carcinoembryonic antigen (CEA)-have been used as a noninvasive method of identifying ovarian cancer in conjunction with imaging. Although current guidelines do not recommend use of STMs as screening tools for ovarian cancer, these markers have clinical utility in both diagnosis and surveillance for women with ovarian cancer. CA-125 is the most commonly used STM; its level may be elevated in several types of ovarian cancer, including epithelial cell tumors, carcinosarcoma, teratomas, and secondary ovarian malignancies. An elevated level of CA 19-9 is associated with clear cell tumors, teratomas, and secondary malignancies. CEA is most commonly associated with mucinous ovarian cancers. Finally, HE4 is being increasingly used to identify certain subtypes of epithelial ovarian cancers, particularly serous and endometrioid tumors. Diagnosis of ovarian cancers relies on a combination of CA-125 levels and US findings, which include a large adnexal mass or high-risk features, including septa and increased vascularity. CT is preferred for staging and is used along with PET and STM monitoring for surveillance. Increasingly, MRI is being used to characterize ovarian lesions that are indeterminate at US or CT. The future of STM testing involves development of "liquid biopsies," in which plasma samples are analyzed for evidence of tumors, including circulating tumor DNA or tumor cells and tumor micro-RNA. When combined with traditional imaging techniques, liquid biopsies may lead to earlier diagnosis and improved survival. An invited commentary by Shinagare is available online. ©RSNA, 2021.

Serum Human Epididymis Protein 4 is a Potential Biomarker for Early Chronic Kidney Disease in an Obese Population [Retraction

[This retracts the article DOI: 10.2147/DMSO.S300940.].