Human Epididymis Protein Research Articles

The diagnostic accuracy of HE4 in the differential diagnosis of pleural effusions

BackgroundPleural effusions are challenging to diagnose, with approximately 20–50% of malignant effusions not diagnosed by cytology. Human epididymal protein 4 (HE4) may be useful in the differential diagnosis of pleural effusions. In serum, this biomarker shows false-positive results in some benign diseases. The aim of this study was to evaluate the diagnostic utility of HE4 in this setting and to identify false positives. MethodsConcentrations of HE4, adenosine deaminase, % polynuclear cells, and C-reactive protein, were determined in 238 pleural fluid samples and the estimated glomerular filtration rate (eGFr) in serum. ResultsHE4 values ​​differed significantly (p < 0.01) between malignant [median (IQR)] [1065 (2085)] pmol/L and benign effusions [699 (589)] pmol/L. HE4 concentrations in gynecological and pulmonary tumors were significantly higher than in other tumors.For a cut-off point of 3050 pmol/L, 22 % sensitivity and 100 % specificity were obtained.In patients with benign disease, significant increases in HE4 were identified only in those with eGFr < 30 mL/min/1.73 m2 [1050(596)] pmol/L, and not in those with eGFr > 30 mL/min/1.73 m2 [597(532)] pmol/L).Two cut-offs were established for maximum specificity, depending on the eGFr: 3050 pmol/L for eGFr < 30 mL/min/1.73 m2 and 1992 pmol/L for eGFr > 30 mL/min/1.73 m2. A sensitivity of 28.5 % was obtained for patients with eGFr > 30 mL/min/1.73 m2 and 36.3 % for patients with eGFr < 30 mL/min/1.73 m2. The sensitivity using a specific cut-off point was 29.7 %. ConclusionsThe determination of HE4 in pleural fluids demonstrates high specificity and low sensitivity. The use of specific cutoff points that are clinically adjusted improves sensitivity while maintaining maximum specificity.

Investigating the role of human epididymis protein 4-mediated immunosuppression in ovarian cancer

Investigating the role of human epididymis protein 4-mediated immunosuppression in ovarian cancer

Research progress on correlative prediction factors and prediction models of endometriosis associated ovarian carcinoma.

Endometriosis is a common benign disease in women of childbearing age, with a malignant change rate of about 1%. Endometriosis associated ovarian cancer (EAOC), which usually occurs in the ovaries, is a serious threat to women's health. Early identification of high-risk groups of EMs malignant transformation is of great significance for the prevention and treatment of EAOC. However, there is still a lack of specific and sensitive prediction factors. In recent years, scholars at home and abroad have used traditional statistical methods and machine learning to explore EAOC related prediction factors and prediction models. This paper mainly reviews and evaluates the diagnosis and prediction model of EAOC. Studies were identified by searching the CNKI, PubMed and Web of Science Core Collection, (WOSCC) till 2023, Data which met the inclusion criteria of clinical studies were evaluated about the quality. This paper analyzes and summarizes the prediction factors and prediction models in the literature. After screening, 7 relevant studies were finally obtained. Prediction factors included: age, menstruation, menopausal status, course of disease, infertility associated with endometriosis, history of single estrogen use during menopause, serological indexes: human epididymis protein 4, carbohydrate antigen 125(CA125), ovarian malignancy risk algorithm, indications for ultrasound examination: cyst shape, structure and blood flow signal, etc. Prediction models: Alignment diagram, Multivariate logistic regression model, Gail model, Gradient Boosting Decision Tree and Lasso-logistics regression. Related models were in good agreement with the actual situation, and have good sensitivity and specificity. The relevant prediction factors and prediction models were summarized to provide reference and new thinking for the research of prediction models in the field of EAOC, in order to develop standardized long-term management strategies for high-risk groups of EAOC and realize the advance of the diagnosis threshold of patients with EAOC.

Diagnostic role of urine human epididymis protein 4 in ovarian cancer.

Ovarian cancer is the 8th most common malignancy in women and the deadliest gynecological cancer. Due to the non-specific symptoms and the lack of effective diagnostic methods, late diagnosis remains the main barrier for improving the poor prognosis. Human epididymis protein 4 (HE4) is a protein overexpressed in ovarian cancer, but not in healthy individuals or benign conditions. The aim of this review article is to evaluate the laboratory aspect and potential clinical application of urine HE4. The methodology is presented, together with discussion on preanalytical, analytical and postanalytical phase of HE4 detection using urine. Moreover, we present the diagnostic role of urine HE4 in differential diagnosis, chemotherapy response, detection of recurrence and detection of low-malignant potential tumors. It has been found that urine HE4 presents as a promising, non-invasive tumor marker for detection and monitoring of ovarian cancer. However, standardization of the HE4 detection process is needed prior to implementation in clinical diagnostics.

B-314 Utility of he4 in differential diagnosis of pleural effusions

Abstract Background The usefulness of tumor markers in the differential diagnosis of cancer in patients with pleural effusions (PE) remains controversial. Few studies have reported the measurement of human epididymal protein 4 (HE4) in pleural fluid. HE4 is a tumor marker associated with different types of cancer. An elevated serum concentration has been observed in ovarian and lung cancers. Other benign pathologies can increase HE4 levels, which can be detect with different laboratory tests identified with adenosine deaminase (ADA), C-reactive protein (CRP), % polynuclear cell count (%PMN) and glomerular filtration rate (GFR) can be used in order to detect possible false positives. The objective of this study was to assess the diagnostic usefulness of HE4 in malignant pleural effusions by comparing HE4 concentrations between benign and malignant samples, while considering the causes of HE4 false positives. Methods HE4, ADA, differential leukocyte count, CRP and GFR concentrations were determined in 238 pleural effusion samples. Diagnostic efficacy analysis using receiver operating curves (ROC) identified the ability of HE4 to detect malignancy, searching for cut-off points with 100% specificity. Results HE4 concentrations showed significant differences (P&amp;lt;0.01) between malignant (median 1065pmol/L) and benign (median 699pmol/L) pleural effusions. Significant differences (P&amp;lt;0.01) were found in HE4 concentrations for gynecological and lung cancer origin (median 7397 pmol/L and 5150 pmol/L respectively) and other malignant pleural effusions (median 1065 pmol/L). Patients with benign diseases with renal failure showed a higher HE4 concentration (median 964pmol/L) than in patients without these pathologies (median 696pmol/L) identified with GFR&amp;lt;30 mL/min. No differences were demonstrated in HE4 concentration levels using ADA, differential leukocyte count or CRP, so only glomerular filtration rate was considered cause of false positives. A sensitivity of 23% was obtained for HE4, with a cut-off point of 3050pmol/L and a specificity of 100% for the whole group. In the potential false positive group, the sensitivity of HE4 was 28% with a cutoff point of 3050 pmol/L with a specificity of 100%. In the group without potential false positives, we obtained a sensitivity of 30% with a specificity of 100% for a cutoff point of 1992pmol/L. When we used a specific cut-off point for each group, we obtained a sensitivity of 38% with a specificity of 100%. Conclusions HE4 levels are higher in malignant pleural effusions compared to other pathologies. HE4 levels allow the identification of malignant pleural effusions with moderate sensitivity and maximum specificity. HE4 levels can differentiate between tumors of gynecological or lung origin and others. Glomerular filtration rate (GFR&amp;lt;30 mL/min) was considered the main cause of false positives. If we identify possible false positives, we can use specific cut-offs and improve sensitivity up to 38% with maximum specificity compared to using a single cut-off for all effusions.

Sensitive and Cost-Effective Tools in the Detection of Ovarian Cancer Biomarkers.

Women diagnosed with late-stage ovarian cancer suffer a very high rate of mortality. Accordingly, it is imperative to detect and diagnose the disease as early as possible in its development. Achievement of this aim implies relatively large-scale screening of women at an age of clinical significance through assay of biomarkers for disease present in blood or serum. Biosensor detection offers an attractive technology for the automated detection of such species. Among several biomarkers that have been identified that are present in patients with ovarian cancer, the only one that is commonly tested for in clinical use is cancer antigen 125, which is considered to be a poor biomarker for the disease. Here, we describe several biosensors that developed in the past decade for the detection of ovarian cancer biomarkers such as CA125, human epididymis protein 4 (HE4) and apolipoprotein A1. The challenges presented by the fabrication of biosensor devices for detecting ovarian cancer and the limited number of biosensors developed for this purpose are discussed.

Serum human epididymis Protein-4 outperforms conventional biomarkers in the early detection of non-small cell lung cancer

Serum human epididymis Protein-4 outperforms conventional biomarkers in the early detection of non-small cell lung cancer

Diagnostic performances of the Ovarian Adnexal Reporting and Data System, the Risk of Ovarian Malignancy Algorithm, and the Copenhagen Index in the preoperative prediction of ovarian cancer: a prospective cohort study.

This study aimed to assess the diagnostic performance of the Risk of Ovarian Malignancy Algorithm (ROMA), Copenhagen Index (CPH-I), and Ovarian Adnexal Reporting and Data System (O-RADS) for the preoperative prediction of ovarian cancer (OC). A prospective cohort study was conducted on 462 patients diagnosed with ovarian tumors admitted to the Departments of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy Hospital, and Hue Central Hospital from May 2020 to December 2022. ROMA and CPH-I were calculated using cancer antigen 125 (CA125), human epididymal protein 4 (HE4) levels, and patient characteristics (age and menopausal status). O-RADS criteria were applied to describe ovarian tumor characteristics from ultrasound findings. Compared with histopathological results, the predictive values of ROMA, CPH-I, and O-RADS alone or in combination with CA125/HE4 for OC were calculated. Among 462 patients, 381 had benign tumors, 11 had borderline tumors, and 50 had OC. At optimal cut-off points, ROMA's and CPH-I's areas under the curves (AUCs) were 0.880 (95% confidence interval [CI]=0.846-0.909) and 0.890 (95% CI=0.857-0.918), respectively, and ROMA and CPH-I sensitivities/specificities (Se/Sp) were 68.85%/95.01% and 77.05%/91.08%, respectively. O-RADS ≥3 yielded an AUCs of 0.949 (95% CI=0.924-0.968), with Se/Sp of 88.52%/88.98% (p<0.001). Combining O-RADS with CA125 demonstrated the highest predictive value, with AUCs of 0.969 (95% CI=0.949-0.983) and Se/Sp of 98.36%/86.09% (p<0.001). The ROMA, CPH-I, O-RADS, O-RADS + CA125, and O-RADS + HE4 models demonstrated good predictive values for OC; the combination of O-RADS and CA125 yielded the highest values.

Potential for trans-pulmonary tumor markers in the early diagnosis of lung cancer: a case report

BackgroundMeasurement of tumor markers from peripheral venous blood is an emerging tool to assist in the early diagnosis of lung cancer. Samples from the pulmonary artery and pulmonary artery wedge position (trans-pulmonary samples) are accessible via right-heart catheterization and, by virtue of their proximity to lung tumors, may increase diagnostic yield.Case presentationWe report a case of a 64 year-old woman from whom trans-pulmonary samples were obtained and who was diagnosed 16 months later with recurrent metastatic small cell lung cancer. Carcinoembryonic antigen, cytokeratin fragment 21 − 1 (CYFRA), and human epididymis protein 4 (HE4) levels demonstrated increasing concentrations across the pulmonary circulation. These gradients exceeded the assays’ coefficient of variation by several-fold. For CYFRA and HE4, pulmonary artery wedge concentrations exceeded peripheral venous levels by more than 10% and peripheral arterial levels were up to 8% higher than peripheral venous levels.ConclusionsEvaluating the feasibility and utility of trans-pulmonary tumor markers for lung cancer diagnosis in a larger cohort should be considered. The addition of a peripheral arterial sample to standard peripheral venous samples may be a more practical alternative.

Adult Uterine Wilm’s Tumor Miss-interpreted as Carcinosarcoma: A Case Report

Introduction: Wilm’s tumor (WT) is a common renal malignancy in children. Adult extrarenal WT involving the uterus is extremely rare. Herein, we reported a case of uterine WT in an old woman who was primarily diagnosed with carcinosarcoma. Case Presentation: A 63-year-old woman presented with abdominal pain and radiologic evidence of pelvic mass originating from the uterus, which was suggestive of sarcoma. Her Serum levels of Cancer Antigen 125 (CA125), Human Epididymis protein 4 (HE4), Cancer Antigen 19-9 (CA19-9), and Alpha Fetoprotein (AFP) were found to be elevated. She underwent total hysterectomy, bilateral salpingo-oophrectomy, and omentectomy. Pathologic examination of the specimens revealed a large uterine mass with serosal surface and omental invasion. The initial diagnosis was carcinosarcoma based on the mixed epithelial and mesenchymal components observed on microscopic examination. Triphasic components of papillary, primitive tubules, and glomeruloid structures, along with mesenchymal and blastemal elements were identified upon second opinion. An immunohistochemistry (IHC) study revealed positive reactions for WT1, CKAE1 /AE3, EMA, Glypican-3, and CD56 in all components of the tumor cells. P53 expression was normal. GATA3, ER, PR, and CD10 were negative. The final diagnosis was changed to WT. Conclusions: Uterine WT is an extremely rare malignancy, which could be associated with elevated serum AFP. Diagnosis and treatment of these rare tumors pose challenges for both pathologists and clinicians.

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

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

The diagnostic performance of the Mindray system in detecting CA125 and HE4 for patients with ovarian cancer.

Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the most commonly used tumor biomarkers for ovarian cancer (OC) screening and diagnosis. The risk of ovarian malignancy algorithm (ROMA) score uses these markers, as detected by the Roche system, to predict the risk of OC. This study sought to assess the performance of the Mindray system in detecting CA125 and HE4 for ROMA score calculation in clinical settings. Consecutive OC patients and patients with benign pelvic masses were screened and enrolled in this study. The CA125 and HE4 levels of these patients were measured using both the Mindray and Roche systems. The ROMA score for each patient was calculated. Diagnostic performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The HE4 and CA125 levels were significantly higher in the patients with OC than the patients with benign ovarian masses. Both detection systems showed high efficiency in detecting ovarian cancer. For the premenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.866, 0.852, and 0.879, respectively, using the Roche system, and 0.911, 0.902, and 0.883, respectively, using the Mindray system. For the postmenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.962, 0.920, and 0.953, respectively, using Roche system, and 0.966, 0.924, and 0.959, respectively, using the Mindray system. The correlation analysis showed strong agreement between the two systems. Among the patients who experienced recurrence, we observed a significant increase in both HE4 and CA125 levels compared to baseline using the Mindray system. The Mindray and Roche systems provide consistent results. The Mindray system can be used to detect HE4 and CA125 for ROMA score calculation.

The Value of Human Epididymal Protein 4, Carcinoembryonic Antigen and Alpha-Fetoprotein in the Early Diagnosis of Cervical Cancer

Objectives: This research aimed to unveil the value of human epididymal protein 4 (HE4), carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in the early diagnosis of cervical cancer. Design: This was a clinical study. Participants: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with cervical intraepithelial neoplasia (CIN) (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. Setting: The review was conducted in a Jiaxing First Hospital. Methods: Sixty patients with cervical cancer stage IA-IIA (early stage cervical cancer group), 60 patients with CIN (disease control group), and 60 healthy women who had passed the physical examination (healthy control group) were selected. The expression levels of serum HE4, CEA, and AFP in the three groups were detected, and the correlation between the levels of serum HE4, CEA, and AFP and the clinicopathological characteristics of patients with early stage cervical cancer were analyzed, and the receiver operating characteristic (ROC) curves were plotted to identify the value of the single and triple tests of serum HE4, CEA, and AFP for the early stage diagnosis of cervical cancer. Results: The levels of serum HE4, CEA, and AFP in the early stage cervical cancer group were higher than those in the disease control and the healthy control groups (p < 0.05). The levels of serum HE4, CEA, and AFP were related to the FIGO stage as well as the histological grading of patients with early stage cervical cancer (p < 0.05). The results of the ROC curves revealed that the AUC areas of HE4, CEA, and AFP for single as well as triple diagnosis of patients with early stage cervical cancer were 0.725, 0.679, 0.663, and 0.811, respectively, and the AUC of the three combined tests was markedly higher than that of HE4, CEA, AFP single test (p < 0.05). Limitations: There is a lack of larger sample sizes to test whether the combined HE4, CEA, and AFP detection has sufficient validity at the individual level and there are not enough serum samples in this study to perform circulating HPV-DNA detection and compare it with the levels of serum markers. Conclusion: The combination of HE4, CEA, and AFP has good clinical reference value analysis in the auxiliary diagnosis of early stage cervical cancer, and it is worthy of further validation and popularization.

Comprehensive serum glycopeptide spectra analysis to identify early-stage epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is widely recognized as the most lethal gynecological malignancy; however, its early-stage detection remains a considerable clinical challenge. To address this, we have introduced a new method, named Comprehensive Serum Glycopeptide Spectral Analysis (CSGSA), which detects early-stage cancer by combining glycan alterations in serum glycoproteins with tumor markers. We detected 1712 glycopeptides using liquid chromatography–mass spectrometry from the sera obtained from 564 patients with EOC and 1149 controls across 13 institutions. Furthermore, we used a convolutional neural network to analyze the expression patterns of the glycopeptides and tumor markers. Using this approach, we successfully differentiated early-stage EOC (Stage I) from non-EOC, with an area under the curve (AUC) of 0.924 in receiver operating characteristic (ROC) analysis. This method markedly outperforms conventional tumor markers, including cancer antigen 125 (CA125, 0.842) and human epididymis protein 4 (HE4, 0.717). Notably, our method exhibited remarkable efficacy in differentiating early-stage ovarian clear cell carcinoma from endometrioma, achieving a ROC-AUC of 0.808, outperforming CA125 (0.538) and HE4 (0.557). Our study presents a promising breakthrough in the early detection of EOC through the innovative CSGSA method. The integration of glycan alterations with cancer-related tumor markers has demonstrated exceptional diagnostic potential.

The clinical importance of IFN-γ and human epididymis protein 4 in Egyptian patients with epithelial ovarian cancer combined with HPV infection

BackgroundHigh-grade Epithelial Ovarian Cancer (HGEOC) is an aggressive disease that usually presents at an advanced stage. Thus, detecting the circulating cytokines (IFNγ and TNF-α) may serve as a biomarker to identify malignancy and manage therapeutic decisions. ObjectivesAssessing the clinical importance of inflammatory mediators and tumor markers in EOC Egyptian patients compared with benign cases. Moreover, identifying the distinct inflammatory mediators in EOC patients combined with HPV infection. MethodsThis study was conducted on 61 Egyptian patients, divided into 25 patients with HGEOC, 22 patients with LGEOC, and 14 benign ovarian tumor cases. Measurements of serum HE4, CA125, CEA, and CA19-9 were determined by Roche Elecsys immunoassays. Serum levels of TNF-α and IFN-γ were measured using quantitative sandwich ELISA. Quantitative genotyping of HPV DNA types 16, 18, and 45 was assessed for the HPV DNA-positive samples. ResultsHPV DNA was detected in 25.53 % of malignant cases, HPV 16 was detected in 50 % of HPV-positive cases, and only 1 case of HPV 18 was detected out of 12 positive cases. The Human Epididymis protein 4 (HE4) was statistically different between patients with EOC and benign cases (p-value = 0.007) and between HPV DNA positive and HPV DNA negative cases (p-value = 0.008). The serum levels of IFN- γ were statistically different between HGEOC and LGEOC (p-value < 0.001), while the serum levels of TNF-α didn’t differ statistically between the two groups. ConclusionIFN-γ could be used as a biomarker to discriminate HGEOC and LGEOC. Initial evidence for the possible association between HE4 and the progression of HPV-associated EOC was speculated.

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.

Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study.

The plasma proteome can mediate associations between periodontal disease (Pd) and brain white matter integrity (WMI). We screened 5089 UK Biobank participants aged 40-70 years for poor oral health problems (POHP). We examined the association between POHP and WMI (fractional anisotropy (FA), mean diffusivity (MD), Intracellular Volume Fraction (ICVF), Isotropic Volume Fraction (ISOVF) and Orientation Diffusion (OD)), decomposing the total effect through the plasma proteome of 1463 proteins into pure mediation, pure interaction, neither, while adjusting for socio-demographic and cardiovascular health factors. Similarly, structural equations modeling (SEM) was conducted. POHP was more prevalent among men (12.3% vs. 9.6%), and was associated with lower WMI on most metrics, in a sex-specific manner. Of 15 proteins strongly associated with POHP, growth differentiation factor 15 (GDF15) and WAP four-disulfide core domain 2 (WFDC2; also known as human epididymis protein 4; HE4) were consistent mediators. Both proteins mediated 7-8% of total POHP effect on FAmean. SEM yielded significant total effects for FAmean, MDmean and ISOVFmean in full models, with %mediated by common latent factor (GDF15 and WFDC2) ranging between 13% (FAmean) and 19% (ISOVFmean). For FA, mediation by this common factor was found for 16 of 49 tract-specific and global mean metrics. Protein metabolism, immune system, and signal transduction were the most common pathways for mediational effects. POHP was associated with poorer WMI, which was partially mediated by GDF15 and WFDC2.

Prediction of postoperative residual primary ovarian neoplasm or metastatic lesion close to rectum of serous ovarian carcinoma based on clinical and MR T1-DEI features.

The optimal primary debulking surgery outcome of serous ovarian carcinoma (SOC) is greatly affected by primary ovarian neoplasm or metastatic lesion close to the rectum. To study the risk factors affecting postoperative residual primary ovarian neoplasm or metastatic lesion close to the rectum of SOC. The clinical and MRI data of 164 patients with SOC eligible from institution A (training and test groups) and 36 patients with SOC eligible from institution B (external validation group) were collected and retrospectively analyzed. The clinical data included age, serum carbohydrate antigen 125 (CA-125), human epididymis protein 4, and neutrophil-to-lymphocyte ratio (NLR). Magnetic resonance imaging (MRI) data included ovarian mass distribution, maximum diameter of ovarian mass, ovarian mass features, degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion, and amount of ascites. A model was established using multivariate logistic regression. By univariate and multivariate logistic regressions, CA-125 (P = 0.024, odds ratio [OR] = 3.798, 95% confidence interval [CI] = 1.24-13.32), NLR (P = 0.037, OR = 3.543, 95% CI = 1.13-12.72), and degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion (P < 0.001, OR = 37.723, 95% CI = 7.46-266.88) were screened as independent predictors. The area under the curve values of the model in the training, test, and external validation groups were 0.860, 0.764, and 0.778, respectively. The clinical-radiological model based on T1-weighted dual-echo MRI can be used non-invasively to predict postoperative residual ovarian neoplasm or metastasis close to SOC in the rectum.

Three-Dimensional Structure of Human Epididymis Protein 4 (HE4): A Protein Modelling of an Ovarian Cancer Biomarker Through In Silico Approach

The Human Epididymis Protein 4 (HE4) biomarker has been extensively investigated for its potential in diagnosing ovarian cancer (OC). For the application of diagnostic techniques and drug delivery, it is crucial to understand the protein tertiary structure. However, the Protein Data Bank (PDB) does not currently contain the three-dimensional (3D) structure of HE4. Therefore, an in silico analysis was conducted to model the HE4 protein using AlphaFold, I-TASSER, and Robetta servers, with the sequence retrieved from UniProt (ID: Q14508). These three servers employed deep learning algorithms, threading templates, and de novo methods, respectively. Subsequently, Molecular Dynamics (MD) simulation using the GROMACS software package improved each 3D structure model, resulting in optimized and refined structures: RF1, RF2, and RF3. PROCHECK and ERRAT programs were employed to assess the structure quality. The Ramachandran plots from PROCHECK indicated that 100% of residues were within the allowed regions for all servers except for I-TASSER. For the refined structures, RF1 and RF3, all residues were concentrated within the allowed regions. According to the ERRAT program, the RF1 model exhibited the highest overall quality factor of 97.701, followed by RF3 and AlphaFold models with scores of 94.643 and 93.750, respectively. After these validations, RF1 emerged as the most accurately predicted 3D structure of HE4 and has one tunnel identified by CAVER 3.0 tool that facilitates the transportation of small particles to the active site, supported by FTsite and PrankWeb binding site predictions. This model holds potential for various computational studies, including the development of OC diagnostic kits. It will enhance our comprehension of the interactions between the protein and other biomolecules.

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

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. 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). 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. 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.