Human Epididymis Research Articles

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

Biomarkers of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

BackgroundInterstitial Lung Disease (ILD) represents the most common extra-articular manifestation of Rheumatoid Arthritis (RA) and is a major cause of mortality. This study aims to identify and evaluate biomarkers associated with Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD).MethodsWe searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for studies related to biomarkers of RA-ILD up until October 7, 2023. The Newcastle-Ottawa Scale (NOS) and standards recommended by the Agency for Healthcare Research and Quality (AHRQ) were used for quality assessment, and meta-analysis was conducted using Stata18.0 software.ResultsA total of 98 articles were assessed for quality, 48 of which were included in the meta-analysis. 83 studies were of high quality, and 15 were of moderate quality. The meta-analysis showed significant differences in biomarkers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody, Rheumatoid Factor (RF), Krebs von den Lungen-6 (KL-6), Surfactant Protein D (SP-D), Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 19-9 (CA19-9), Matrix Metalloproteinase-7 (MMP-7), C-X-C Motif Chemokine Ligand 10 (CXCL-10), and Neutrophil-to-Lymphocyte Ratio (NLR) between RA-ILD patients and RA patients. However, Platelet-to-Lymphocyte Ratio [Platelet-to-Lymphocyte Ratio (PLR)], Cancer Antigen 125 [Cancer Antigen 125 (CA-125)], and Cancer Antigen 153 [Cancer Antigen 153 (CA-153)] did not show significant differences between the two groups. KL-6, MMP-7, and Human Epididymis Protein 4 (HE4) are negatively correlated with lung function, and KL-6 is associated with the prognosis of RA-ILD.ConclusionsBiomarkers hold promising clinical value for prediction, diagnosis, severity assessment, and prognosis evaluation in RA-ILD. However, these findings need to be validated through multicenter, large-sample, prospective cohort studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023448372.

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.

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

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.

Human efferent ductules and epididymis display unique cell lineages with motile and primary cilia.

Previous research has illustrated the role of cilia as mechanical and sensory antennae in various organs within the mammalian male reproductive system across different developmental stages. Despite their significance in both organ development and homeostasis, primary cilia in the human male reproductive excurrent duct have been overlooked due to limited access to human specimens. This study aimed to characterize the unique cellular composition of human efferent and epididymal ducts, with a focus on their association with primary cilia. Human efferent ductules/epididymides from five donors aged 32-47 years, were obtained through our local organ transplant program. Cell lineage specificity and primary cilia features were examined by immunofluorescent staining and confocal microscopy in the efferent ductules and the distinct segments of the epididymis. The epithelium of the human efferent duct exhibited estrogen receptor-positive cells with primary cilia, FoxJ1-positive multiciliated cells with numerous motile cilia, and non-ciliated intraepithelial immune cells. Notably, intraluminal macrophages, identified by CD163/CD68 positivity, were observed to engage in sperm phagocytosis. In all three segments of the human epididymis, primary cilia were found on the surface of principal and basal cells. Our research indicates that the human efferent ductules create a distinct environment, characterized by the presence of two types of ciliated cells that are in contact with immune cells. The discovery of sensory primary cilia exposed on the surface of reabsorptive cells in the efferent ductules, as well as on basal and principal cells in the epididymis, lays the foundation for complementary functional studies. This research uncovers novel characteristics exclusive to human efferent ductules and epididymides, providing a basis for exploring innovative approaches to male contraception and infertility treatment.

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.

Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens.

The endoplasmic reticulum (ER) is the central hub for protein quality control, where the protein disulfide isomerases (PDIs), encoded by at least 21 genes, play a pivotal role. These multifunctional proteins contribute to disulfide bond formation, proper folding, and protein modifications, and may act as hormone-binding proteins (e.g., steroids), influencing hormone biology. The interplay between ER proteostasis, PDIs, and epididymis-a crucial site for sperm maturation-remains largely understudied. This study characterizes transcriptional signatures of Pdi genes in the epididymis. Transcriptional profiles of selected Pdi genes were assessed in adult Wistar rat tissues, and epididymis under different experimental conditions (developmental stages, surgical castration, and efferent ductules ligation [EDL]). In silico bioinformatic analyses identified expression trends of this gene family in human epididymal segments. P4hb, Pdia3, Pdia5, Pdia6, Erp44, Erp29, and Casq1 transcripts were detected in both reproductive and non-reproductive tissues, while Casq2 exhibited higher abundance in vas deferens, prostate, and heart. Pdilt, highly expressed in testis, and Pdia2, highly expressed in heart, showed minimal mRNA levels in the epididymis. In the mesonephric duct, epididymal embryonic precursor, P4hb, Pdia3, Pdia5, Pdia6, and Erp29 mRNAs were found at gestational day (GD) 17.5. Except for Erp29, which remained stable, these Pdi transcript levels increased from GD17.5 to GD20.5, when epididymal morphogenesis occurs, and were maintained to varying degrees in the epididymis during postnatal development. Surgical castration downregulated P4hb, Pdia3, Pdia5, Pdia6, Pdilt and Erp29 transcripts, an effect reversed by testosterone replacement. Conversely, transcript levels remained unaffected by EDL, except P4hb, which was reduced in caput epididymis. All 21 PDI genes exhibited diverse transcriptional profiles across the human epididymis. The findings lay the foundations to explore Pdi genes in epididymal biology. As a considerable proportion of male infertility cases are idiopathic, targeting hormonal regulation of protein quality control in epididymis represents a route to address male infertility and advance therapeutic interventions in this domain.

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.

P-314 Is there a relationship between adenomyosis ultrasonographic findings and serum Human epididymis protein 4 (HE4) ?

Abstract Abstract withdrawn by the authors