HE4 Concentrations Research Articles

HE4 and CA-125 kinetics to predict outcome in patients with recurrent epithelial ovarian carcinoma: the META4 clinical trial.

HE4 and CA-125 are used for epithelial ovarian cancer (EOC) screening, diagnosis, and follow-up. Our objective was to study HE4 and CA-125 kinetics in patients treated for recurrent EOC. Serum samples were prospectively collected before the first chemotherapy cycle and every 3 months until disease progression. Data from 89/101 patients could be analyzed. At baseline, the median CA-125 and HE4 concentrations were 210 IU/L (7-10,310) and 184 pM (31-4,836). Among the 12 patients (13%) with normal CA-125 (<35 IU/L) concentration, eight had HE4 concentration ≥75 pM, and among the 16 patients with normal HE4 concentration (18%), 12 had increased CA-125 concentration. The median nadir concentrations were 31 IU/L (3-8,744) for CA-125 and 75 pM (20-4,836) for HE4. The median times to nadir were 14 (0-130) weeks for CA-125 and 12 (0-52) weeks for HE4. In multivariate analysis, CA-125 and HE4 nadir concentrations (<35 IU/L, HR 0.35, 95% CI: 0.17-0.72 and<75 pM, HR 0.40, 95% CI: 0.20-0.79) and time to CA-125 and HE4 nadir (>14 weeks, HR 0.37, 95% CI: 0.20-0.70 and >12 weeks, HR 0.43, 95% CI: 0.23-0.83) were prognostic factors of progression-free survival. More investigations on HE4 kinetics could help to better monitor patients with CA-125 concentration within normal values.

Point-of-care testing: a disposable label-free electrochemical CA125 and HE4 immunosensors for early detection of ovarian cancer.

Cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are critical biomarkers for ovarian cancer diagnosis and progression monitoring; therefore, sensitive determination of their levels in body fluids is crucial. In recent study, label-free CA125 and HE4 immunosensors were prepared using disposable screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles for the sensitive, fast, and practical determination of CA125 and HE4. Differential pulse voltammetry, square wave voltammetry, and electrochemical impedance spectroscopy methods were used for the electrochemical determination of antigens in four different linear ranges (1-100 pg mL- 1, 0.01-10 ng mL- 1, 10-50 ng mL- 1, and 50-500 ng mL- 1). High sensitivity, low limit of detection, and limit of quantification were obtained for each linear range with a correlation coefficient above 0.99. The application stability of CA125 and HE4 immunosensors was determined as 60 days, and the storage stability was determined as 16 weeks. Immunosensors showed high selectivity in nine different antigen mixtures. The reusability of the immunosensors has been tested up to 9 cycles. The Risk of Ovarian Malignancy Algorithm score% values were calculated using the concentration of CA125 and HE4 in the blood serum and evaluated in terms of ovarian cancer risk. For the point-of-care testing, CA125 and HE4 levels at pg mL- 1 concentration were measured in blood serum samples using the developed immunosensors and a hand-held electrochemical reader in approximately 20-30s, and high recoveries were obtained. These disposable label-free immunosensors are user-friendly and can be used in point-of-care tests for rapid and practical detection of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

A label-free dual immunosensor for the simultaneous electrochemical determination of CA125 and HE4 biomarkers for the early diagnosis of ovarian cancer.

The blood levels of cancer antigen 125 (CA125) and human epididymal secretory protein 4 (HE4) are measured in the diagnosis and progression monitoring of ovarian cancer (OC), and the Risk of Ovarian Malignancy Algorithm (ROMA) score% values are calculated for cancer risk assessment. For the first time, disposable dual screen-printed carbon electrodes modified with reduced graphene oxide, polythionine, and gold nanoparticles were used to fabricate label-free electrochemical dual CA125-HE4 immunosensors for the sensitive, fast, and practical simultaneous determination of CA125 and HE4. DPV and SWV methods were used to simultaneously determine antigens in two different linear ranges (1-100pgmL-1 and 1-50ngmL-1). High sensitivity, low LOD, and LOQ were obtained for two linear ranges with a correlation coefficient above 0.99. The application stability of the dual CA125-HE4 immunosensors was determined as 60days, and the storage stability was determined as 16weeks. The dual immunosensors exhibited high selectivity in eight different antigen mixtures. The reusability of the dual immunosensors has been tested up to 9 cycles. ROMA score% values for pre-menopausal and post-menopausal status were calculated using the concentration of CA125 and HE4 in the blood serum and assessing OC risk. The disposable dual immunosensors can be used in point-of-care tests for rapid and practical simultaneous determination of CA125 and HE4 with high selectivity, sensitivity, and repeatability.

Evaluation of He4 Use in the Diagnosis of Ovarian Cancer: First and Second Recurrence, and an Analysis of HE4 Concentration during Second- and Third-Line Chemotherapy.

HE4 is a commonly used tumor marker for ovarian cancer (OC) diagnosis. In our study, we aimed to assess its use in the diagnosis of subsequent OC recurrences and to evaluate its changes during recurrence diagnosis and the subsequent lines of chemotherapy treatment. This retrospective single center study was conducted on 188 patients treated for ovarian cancer recurrence at the Department of Gynecological Surgery and Gynecological Oncology. The sensitivity and specificity of HE4 for patient survival prediction were analyzed using Receiver Operating Characteristics (ROC) and area under the curve (AUC) with 95% confidence intervals (95% CI). Survival times to reach one of the endpoints (OS, PFS, TFI, PFS2, TFI2) were analyzed using Kaplan-Meier curves. Elevated HE4 levels at the time of first relapse diagnosis, and after the third and the last course of second-line chemotherapy, significantly influences the time from OC diagnosis until first disease recurrence (PFS2) (p = 0.005, p = 0.015 and p = 0.002, respectively). Additionally, elevated serum HE4 concentration at the time of OC diagnosis (p = 0.012), and its later recurrence (first (p < 0.001), and second recurrent diagnosis (p = 0.143)) significantly influences patient OS. Increased HE4 concentration at the end of chemotherapeutic treatment negatively affects overall patient survival ((p = 0.006 for second line chemotherapy and (p = 0.022) for elevated HE4 concentration after the last course of third-line chemotherapy). Our preliminary results show an encouraging diagnostic and prognostic role of HE4 in recurrent ovarian cancer. HE4 measurements at different treatment time points during the second- and third-line chemotherapy treatment seem to correlate with patient survival.

Ovarian-Cancer Biomarker (HE4) Recognition in Serum Using Hetero TFET Biosensor

Recognition of ovarian-cancer biomarker (HE4) in serum using dual-material In <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.53</sub> Ga <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0.47</sub> As/Si hetero-structure charge-plasma-based extended gate TFET biosensor (DCE-HTFET) has been depicted in this paper. The virtual fabrication flow for the configuration has been mentioned here. Silvaco ATLAS TCAD device simulator is used to optimize the device for better sensitivity. The sensitivity of the proposed model in the serum biosphere for different HE4 concentrations in histological subgroups of ovarian cancer has been investigated. An optimum ON-current to OFF-current sensitivity (S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ION/IOFF</sub> ) of 18.2×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">6</sup> and sensitivity regarding sub-threshold swing (S <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">SS</sub> ) of 95% have been achieved for the “Mucinous” type histological sub-group of ovarian-cancer biomarker having 74 pmol/L concentration. The proposed biosensor has been compared with the state-of-the-art literature to highlight its efficacy.

HE4 is associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients.

To explore whether HE4 was associated with clinical risk prognostic factors and survival outcome in primary fallopian tube carcinoma patients. Ninety-six primary fallopian tube carcinoma (PFTC) patients from March 2011 to June 2019 were enrolled in this study. Serum CA125 and HE4 concentrations were measured at four time points including primary diagnosis, postsurgery, pre-recurrence, and recurrence. The relations between clinical risk prognostic factors with HE4 concentrations were investigated, and multivariate survival analysis was used to calculate the hazard ratios between HE4 levels with recurrence-free survival and overall survival. HE4 were significantly elevated in poor performance status, advanced stage, high histological grade and residual tumor diameter >1 cm, and positive lymph node status, respectively, compared with those in well performance status, early stage, low histological grade, residual tumor diameter ≤1 cm, and negative lymph node status, respectively. Multivariate survival analysis indicated serum HE4 can predict outcome of recurrence-free survival and overall survival with hazard ratios of 9.92 (95% confidence interval [CI]: 2.95-33.32) and 3.12 (95% CI: 1.07-9.08), respectively. HE4 is associated with clinical risk prognostic factors in PFTC and contributes to predict survival outcome in PFTC cases.

Evaluation of patients with advanced epithelial ovarian cancer before primary treatment: correlation between tumour burden assessed by [18F]FDG PET/CT volumetric parameters and tumour markers HE4 and CA125.

Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution.

Determination of the Upper Reference Limit of Human Epididymis Secretory Protein 4 (HE4) in Healthy Male Individuals and Correlation with Renal and Fertility Markers

Elevated human epididymis secretory protein 4 (HE4) serum levels have been widely investigated in patients with ovarian cancer. However, high levels of HE4 can be also found in other tumors and in renal fibrosis. To date, the HE4 assay manufacturer features the reference value only for the female pre- and post-menopausal population. The aim of this study was to determine the upper reference limit (URL) of HE4 in a well-defined and large cohort of healthy male individuals and investigate potential factors influencing HE4 levels in healthy subjects. The study included 307 Italian healthy male individuals. HE4 was measured using a chemiluminescent assay (Abbott Laboratories, Wiesbaden, Germany). The URL was calculated using the non-parametric percentile method. Differences in HE4 concentrations according to age, estimated glomerular filtration rate (eGFR), free and bioavailable testosterone were also evaluated. The 97.5th percentile URL of serum HE4 in our study population was 57 pmol/L (90% CI). After stratifying subjects according to age, we found that the URL of HE4 was higher in older (&gt; 50 years) than in younger subjects (18-30 years old), and overlapping with the URL in males from 31 to 50 years old (P=4.769e-16, r=0.44). A strong negative correlation between HE4 and eGFR was observed (P=8.412e-12, r=-0.38). Moreover, a statistically significant negative correlation was also found between HE4 and free and bioavailable testosterone. This study determined the URL of HE4 in a large cohort of healthy male subjects. Our findings indicate that the HE4 age-dependent differences in males need to be taken into account. The definition of the HE4 URL in males and the correlation observed with eGFR and testosterone should foster the clinical use of HE4 beyond gynecologic cancer.

Evaluation of Serum Human Epididymis Secretory Protein 4 (HE4) in Benign Endometrial Disease and Endometrial Cancer

Abstract Objective The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women are being observed. More than 80% of cases are diagnosed in early stages due to early symptoms like abnormal bleeding. Aim of our study to evaluate the ability of serum HE4 concentration to differentiate between benign endometrial disease and endometrial cancer and ass’s correlation it with prognosis of EC. Material and methods Serum HE4 level was measured in 85 patients with abnormal uterine bleeding. Based on histology after curettage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test Results The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 62 pmol/l. There was a significant difference between Stage (I – II) endometrial cancer, and Stage (III – IV) p = 0.01, Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). Conclusion HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic lymphadenectomy.

The assessment of usefulness of HE4 and CA125 quantification for the diagnostics of endometrial cancer

Endometrial cancer is one of the most prevalent uterine malignancies. This disease occurs mostly in older women, frequently affected with other comorbidities. Hence, it is important to search for novel, less burdensome diagnostic modalities, enabling the objective assessment of the patient’s status and facilitating qualification to relevant risk groups prior to surgical treatment. The aim of this study was to verify the usefulness of CA125 and HE4 in the evaluation of endometrial cancer. The study included 308 women treated at University Hospital No. 2 in Bydgoszcz. The study group included 180 patients operated due to endometrial cancer. The control group included 128 women operated due to perineal statics disorders. The concentrations of tumour markers were measured with ELISA-based ready-to-use diagnostic kits. Patients with endometrial cancer and healthy women differed significantly in terms of HE4 concentrations (P = 0.001). The serum concentration of HE4 in stage I endometrial cancer patients was significantly higher (Me = 88.37 pM) than in healthy women (Me = 46.14) (P = 0.007). The analysis of ROC curves with the determination of the area under curve showed 66.7% sensitivity and 78.1% specificity of HE4. AUC for HE4 amounted to 0.721 and was the highest of all markers. Our analysis revealed that HE4 is useful in the detection of endometrial cancer, while Human Epididymis Protein 4 can potentially be used for screening purposes. CA125 antigen, previously used in the diagnostic process, is useless or may possess limited usefulness. There is a need for further studies on larger populations of female patients.

Serum human epididymis protein 4 concentrations are associated with severity of patients with pulmonary tuberculosis

BackgroundHuman epididymis protein 4 (HE4) has been recognized as a biomarker which elevated in various diseases. The aim of this study was to evaluate the value of serum HE4 in pulmonary tuberculosis (PTB). MethodsSerum HE4 concentrations were determined in 127 PTB, 88 chronic bronchitis (CHB), and 105 healthy control subjects by chemiluminescent microparticle immunoassay. Receiver operating characteristic (ROC) curves and Spearman's correlation analysis were performed for investigating value of HE4. ResultsSerum HE4 concentrations were significantly increased in PTB (62.8 pmol/L, IQR 45.8–90.7), compared with that of CHB (50.2 pmol/L, IQR 42.3–64.3, P = 0.0002) and normal control (35.4 pmol/L, IQR 31.1–42.9, P < 0.0001). ROC curve suggested that the AUC of HE4 used to discriminate PTB from CHB was 0.647 (95% CI, 0.574–0.719), with the cutoff value, sensitivity, specificity, PPV, and NPV at 71.9 pmol/L, 0.417, 0.852, 0.672 and 0.543, respectively. Meanwhile, compared with mild to moderated PTB, the levels of HE4 in advanced PTB were significantly elevated (75.8 vs. 57.7 pmol/L, P = 0.0052). What’s more, the levels of HE4 in PTB were found to be significantly associated with the albumin, CRP, and cavity (r = −0.2996, P = 0.0006, r = 0.265, P = 0.0026, r = 0.4699, P < 0.0001, respectively). ConclusionsElevated serum HE4 concentration could be used as a biomarker for the diagnosis and assessment of disease severity in PTB.

Usefulness of HE4 protein in differentiation of pelvic masses in woman.

IntroductionHE4 protein (human epididymis protein-4), which is the fourth subfraction of human epithelial protein, is a glycoprotein widely used as a tumor marker in ovarian cancer. If was first discovered in the epididymal epithelium and recognized as a protease inhibitor contributing to sperm maturation. The plasma HE4 concentration may also be increased in gynecological pathologies other than ovarian cancer.Material and methodsThe study was conducted between 2016 and 2017 among patients hospitalized in the Academic Department of Gynaecology. A total of 191 women were examined. Depending on the type of pathology which was the reason for hospitalization, 4 groups of patients were identified in the study. The first of these included 30 patients with ovarian cancer, the second 33 patients with benign ovarian lesion, the third 50 patients with endometrial cancer, and the fourth 28 patients with leiomyomas.ResultsThe highest concentration of HE4 protein was found in women with ovarian cancer, and it was statistically significantly higher compared to all other groups. Lower HE4 protein concentration than in women with ovarian cancer was reported in women with endometrial cancer, but it was statistically significantly higher compared to patients with uterine fibroids.ConclusionsThis marker may have significant clinical value in the differentiation of benign ovarian pathology from ovarian cancer. The study confirms the validity of using HE4 results in the assessment of potential malignancy of ovarian and endometrial lesions.

Assessment of diagnostic utility of multivariate diagnostic models in differential diagnosis of ovarian tumors.

Ovarian cancer (OC) diagnosis remains a clinical challenge due to lack of early symptoms and insufficient accuracy of the available diagnostic methods. The purpose of this study was to determine whether osteopontin could be useful in differential diagnosis of ovarian tumors. Serum samples from 92 patients qualified for surgical treatment due to ovarian mass were divided into 2 groups according to the histopathological result: OC including borderline ovarian tumors (n = 39) and benign ovarian tumors (BOTs) (n = 53). CA125, HE4 and osteopontin concentrations were measured in all patients. Areas under the receiver operating characteristic curves (AUC of ROC) were used to compare the discriminative ability of the univariate and multivariate diagnostic models. The addition of osteopontin to ROMA significantly improved the diagnostic performance of the test in 3 of the 5 analyses: 1) in the OC vs BOT group (from AUC of 0.955 to 0.975), 2) in premenopausal women OC vs BOT (from AUC of 0.828 to 0.892) and 3) in the FIGO I-II stage OC vs BOT (from AUC of 0.865 to 0.895). It did not alter the diagnostic performance of multifactor tests in the group of postmenopausal women nor in OC FIGO III-IV stage group. Osteopontin was also the best single marker to differentiate between early stage OC and BOTs (AUC of 0.863). Osteopontin improves the diagnostic performance of a multimarker OC diagnostic test and could be useful in differential diagnosis of ovarian tumors, especially in pre-menopausal women and for early stage OC.

Diagnostic and prognostic value of HE4 in female patients with primary peritoneal carcinoma.

HE4 is a useful tumor marker for the diagnosis of ovarian, endometrial, and fallopian tube carcinoma. The aim of our study was to investigate the value of serum HE4 compared with CA125 in the diagnosis of primary peritoneal carcinoma and the estimation of treatment response and recurrence. Serum HE4 and CA125 concentrations were measured in both primary peritoneal carcinoma patients and benign gynecological disease controls. The treatment response and recurrence were assessed by serum HE4 and CA125 levels in primary peritoneal carcinoma patients. Serum HE4 and CA125 levels were significantly increased in primary peritoneal carcinoma patients compared with benign disease controls ( P<0.001). Compared with CA125, HE4 had lower sensitivity (84.2% vs. 94.7%), but higher specificity (99.2% vs. 85.3%); the combination of HE4 and CA125 led to higher sensitivity and specificity. In the receiver operating characteristic analysis, the area under the curve was 0.956 for HE4, for CA125 was 0.953, for HE4+CA125 was 0.979. Furthermore, HE4 and CA125 were closely associated with treatment response, and our results indicated that primary peritoneal carcinoma patients displayed a larger drop of HE4 compared with CA125 (75.8% vs. 61.5%). Combined with CA125, HE4 elevation better predicted recurrence in primary peritoneal carcinoma patients during the remission period after treatment. This study indicated that the detection of serum HE4 changes may enhance the effectiveness for detecting primary peritoneal carcinoma and estimating the outcome of treatment and recurrence in female primary peritoneal carcinoma patients.

Human epididymis protein 4 concentration is not associated with liver fibrosis and cirrhosis in a case control study

BackgroundHuman epididymis protein 4 (HE4) is an emerging fibrotic biomarker which has been studied in chronic kidney disease cohorts. However, it is unclear if the serum level of HE4 may be altered in patients with liver fibrosis and cirrhosis. Methodswe assessed serum HE4 concentrations in patients (n = 366) with chronic liver diseases (CLD) and compared to matched healthy controls (n = 366). Liver stiffness measurement (LSM) by transient elastography (TE, FibroScan) was also performed on all patients. Liver biopsy was performed on 34 of 366 subjects. Moreover, we analysed a subgroup of patients with confirmed cirrhosis to validate the correlation between HE4 and the severity of cirrhosis. Child-Pugh (CP) score was evaluated in this subgroup. ResultsNo statistically significant differences were observed in the median HE4 level between patients with fibrosis and cirrhosis and controls (median: 56.2 vs. 55 pmol/L, p = .562). Neither were any significant differences found among different groups with Child-Pugh Classes A, B and C (median: 56.9, 58.3 and 52.1 pmol/L, respectively; p = .842). Correlation analysis did not show a significant correlation between HE4 and degree of liver fibrosis according to LSM values or histological assessment (r = 0.159, p = .239; r = 0.045, p = .788). ConclusionsSerum HE4 level does not appear to be associated with fibrotic and cirrhotic liver, suggesting that HE4 may not serve as a valuable clinical biomarker for liver fibrosis and cirrhosis.

Serum human epididymis secretory protein 4 as a potential biomarker of renal fibrosis in kidney transplantation recipients

BackgroundRenal fibrosis remains an important cause of kidney allograft failure. The objective of this study was to evaluate the performance of serum human epididymis secretory protein 4 (HE4) as a biomarker for renal fibrosis in kidney transplant recipients. MethodsA total of 103 kidney transplantation patients were enrolled in this study, and serum HE4 concentrations were detected using the chemiluminescent microparticle immunoassay. Renal biopsy was carried out, and histological findings were assessed by immunohistochemistry. ResultsMedian serum HE4 concentrations were significantly increased in kidney transplant recipients (186.2 pmol/l, interquartile range [IQR] 125.6–300.2) compared with control subjects (34.3 pmol/l, IQR 30.4–42.3, p < 0.0001). Meanwhile, serum HE4 concentrations were significantly increased along with disease severity (p < 0.0001). In addition, we found serum HE4 concentrations to be strongly correlated with the severity of fibrosis (IF/TA 0, 1, 2, and 3: 114.3, 179.0, 197.8, and 467.8 pmol/l, respectively; p < 0.0001) and serum HE4 concentrations significantly correlated with HE4 tissue expression concentrations in renal biopsy. ConclusionsSerum HE4 was increased in kidney transplant recipients with decreased kidney function and renal fibrosis and was correlated with the severity of the disease, suggesting that HE4 has the potential to be used as a novel clinical biomarker for evaluating kidney function and predicting renal fibrosis in kidney transplant recipients.

Suitability assessment of baseline concentration of MMP3, TIMP3, HE4 and CA125 in the serum of patients with ovarian cancer

BackgroundMMP and TIMP play an important role in the degradation of extracellular matrix components which are essential for tumor growth, invasion and metastasis. Aim of this research was to assess MMP3 and TIMP3 as prognostic factors among patients with ovarian cancer.ResultsIt was found that high levels of output MMP3 correlated with shortened overall survival time of patients by 9.7 months. In addition, it has been shown that high concentrations of output MMP3 were significantly associated with a shorter disease free time in median concentrations implemented p = 0.0059. Statistically significant dependence has been shown between an average concentration of TIMP3 protein to the overall survival of patients. The higher output concentration of TIMP3, the longer patients’ survival by 8.9 month. In addition, it was found that high TIMP3 concentrations output were associated with a significantly longer disease free duration at a median concentrations p = 0.007.ConclusionPreliminary research shows that output levels of MMP3 and TIMP3 proteins correlate with overall survival of patients. In some cases also time free of illness.

Clinical importance of serum HE4 and MMP2 levels in endometrial cancer patients

IntroductionEndometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer.AimTo explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer.Materials and methodsIncluded in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012–2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA). MMP2 concentrations were quantified in the serum using multiplex immunoassays.ResultsWe observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium (P=0.002/0.003). The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV) vs low (FIGO I and II) clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3) on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre-menopausal patients and 84% vs 79% in post-menopausal patients.ConclusionHE4 and MMP2 are characterized by high specificity and may be useful as biomarkers in the diagnostics of endometrial cancer. When determined preoperatively, HE4 is correlated with the prognostic factors of endometrial cancer and may be helpful in the planning of individual treatment of endometrial cancer patients.

Microbial Profiles and Tumor Markers From Culdocentesis: A Novel Screening Method for Epithelial Ovarian Cancer [3H

INTRODUCTION: Epithelial ovarian cancer (EOC), the most prevalent type of ovarian cancer, has a low five-year survival rate because it is commonly diagnosed in later stages of disease. There is a critical need for early screening methods to improve mortality outcomes. Specific bacterial populations (microbiome) have been linked to various diseases but not investigated with EOC. We hypothesize that patients with EOC have a unique microbiome and this used in conjunction with tumor markers from culdocentesis and serum, would benefit EOC diagnosis and prognosis. METHODS: Study population includes women aged 30 or older, undergoing surgery for an adnexal mass or ovarian malignancy at two hospitals in Springfield, IL. Exclusion criteria are previous malignancy within last 5 years and inability to perform culdocentesis. On the day of surgery, serum and culdocentesis samples were analyzed for CA-125/HE4 concentrations while culdocentesis samples were also sequenced for bacterial V4 rDNA. Associations of microbial profiles with tumor marker levels will be calculated using models developed for biomarker discovery. RESULTS: Currently, 30 patients (10 EOC, 20 benign) have been analyzed for CA-125/HE4. Preliminary results showed elevated tumor markers in EOC serum and culdocentesis but higher EOC positive and negative predictive values in serum than culdocentesis. Microbial profiles recently identified will be correlated to sample tumor marker levels. CONCLUSION: Culdocentesis tumor marker levels significantly correlated with EOC although less than serum levels. Additional analysis of microbial profiles may advance current screening methods and personalized treatment strategies, potentially increasing survival rates of patients with EOC.

Serum HE4 is correlated to prognostic factors and survival in patients with endometrial cancer.

The extent of surgery and the decision for adjuvant treatment in patients with endometrial cancer (EC) depend on the presence of risk factors for lymph node metastases and disease recurrence. Postoperative markers such as myometrial infiltration and specific mutations can select patients for adjuvant treatment but will not influence surgical planning. A biomarker stratifying patients into low-risk and high-risk groups before surgery could identify patients who benefit from more extensive surgery. Therefore, we evaluated the correlation of serum biomarker HE4 with clinical and recently identified prognostic pathological variables and survival. Patients treated for endometrial cancer between 1994 and 2014 were included. Serum HE4 concentration was measured in preoperatively obtained samples. A total of 88 patients were eligible for analysis. The majority (64%) was diagnosed with endometrioid-type adenocarcinoma. Serum HE4 concentration is significantly associated with stage of disease (p=0.001), deep myometrial invasion (p<0.001), exact depth of myometrial invasion (≥4mm) (p=0.01), tumour-free distance to serosa (≤7mm) (p<0.001), extensive lymph vascular space invasion (p=0.04) and cervical involvement (p=0.001). HE4 concentration and nodal involvement were correlated, although not significant (p=0.17). Serum HE4 is an independent prognostic factor for recurrence-free survival (HR 5.12 per 10-fold increase in HE4, 95% CI 1.54-17.1) and overall survival (HR 7.48 per 10-fold increase in HE4, 95% CI 1.76-31.7). HE4 is a prognostic marker in endometrial cancer and is helpful in addition to other variables for the preoperative risk stratification of patients with endometrial cancer.