Value Of HE4 Research Articles

Diagnostic Utility of Selected Matrix Metalloproteinases (MMP-2, MMP-3, MMP-11, MMP-26), HE4, CA125 and ROMA Algorithm in Diagnosis of Ovarian Cancer.

Ovarian cancer (OC) has an unfavorable prognosis. Due to the lack of effective screening tests, new diagnostic methods are being sought to detect OC earlier. The aim of this study was to evaluate the concentration and diagnostic utility of selected matrix metalloproteinases (MMPs) as OC markers in comparison with HE4, CA125 and the ROMA algorithm. The study group consisted of 120 patients with OC; the comparison group consisted of 70 patients with benign lesions and 50 healthy women. MMPs were determined via the ELISA method, HE4 and CA125 by CMIA. Patients with OC had elevated levels of MMP-3 and MMP-11, similar to HE4, CA125 and ROMA values. The highest SE, SP, NPV and PPV values were found for MMP-26, CA125 and ROMA in OC patients. Performing combined analyses of ROMA with selected MMPs increased the values of diagnostic parameters. The topmost diagnostic power of the test was obtained for MMP-26, CA125, HE4 and ROMA and performing combined analyses of MMPs and ROMA enhanced the diagnostic power of the test. The obtained results indicate that the tested MMPs do not show potential as stand-alone OC biomarkers, but can be considered as additional tests to raise the diagnostic utility of the ROMA algorithm.

Predictive Role of HE4 in Diagnosis of Ovarian Tumors.

Approximately 20% of women develop an ovarian cyst or pelvic mass at some point in their lives. Due to high false positivity of CA-125, women with various benign ovarian tumors simulating malignant masses undergo extensive debulking surgery resulting in increased morbidity. Serum HE4 is a useful test for better discrimination of benign or malignant nature of pelvic masses in preoperative period. Our study gives an update on the biological markers specifically CA-125 and a novel tumor marker HE4 and aims to reduce the debulking surgeries done for benign pathology. The total study population (n = 302) included women who were operated with suspicious ovarian malignant mass (n = 238) with benign (n = 98), borderline (n = 6), and malignant (n = 134) ovarian tumors. Cutoff of CA-125 was 35 U/mL, and for HE4 140pM for postmenopausal and 70pM for premenopausal women were calculated at 86% and 81% accuracy, respectively. Statistical analysis was done using SPSS version 20. The cutoff values of CA-125 were able to differentiate between benign, borderline, and malignant tumors with statistical significance (p < 0.05), whereas the cutoff values of HE4 significantly (p < 0.05) differentiated benign tumors from the malignant tumors, but not from the borderline tumors. Serum CA-125 has significantly higher sensitivity and NPV (95%, 72%, respectively) compared to HE4 (81%, 52%) and combined HE4 plus CA-125 (84%, 59%), whereas specificity, PPV, and AUC were higher for combined CA-125 plus HE4 (93%, 98%, 90%, respectively) compared to HE4 (83%, 95%, 88%) and CA-125 (48%, 88%, 87%). Measuring serum HE4 along with CA-125 in preoperative diagnosis helps in excluding benign ovarian tumors in which CA-125 was falsely raised, especially in center where frozen section is not available, thus potentially decreasing morbid debulking surgeries done for benign ovarian tumors.

CD47—a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features

BackgroundEpithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC.MethodsImmunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan–Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis.ResultsCD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732–0.822). The calibration curve showed good consistency.ConclusionCD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

Diagnostic value of CA125, HE4, and systemic immune-inflammation index in the preoperative investigation of ovarian masses.

This study aimed to ascertain the diagnostic accuracy of CA125, HE4, systemic immune-inflammation index (SII), fibrinogen-to-albumin ratio (FAR), prognostic nutritional index (PNI), and their combination for ovarian cancer (OC) to discover an optimal combined diagnostic index for early diagnosis of OC. A thorough investigation was conducted to ascertain the correlation between these markers and the pathological characteristics of OC, thereby providing a foundation for early identification and treatment of this disorder. One hundred seventy patients with documented OC and benign ovarian tumors (BOTs) treated at Hebei General Hospital between January 2019 and December 2022 were included in this retrospective study. Data analysis was conducted using IBM SPSS Statistics version V26.0, MedCalc Statistical Software version 19.4.0, and the R Environment for Statistical Computing software (R Foundation for Statistical Computing). Isolated CA125 showed the best application value for differentiating benign ovarian tumors from OC when the defined variables were compared separately. The combination of CA125, HE4, FAR, SII, and PNI displayed a greater area under the operating characteristic curve curve than any one of them or other combinations of the 5 variables. Compared to CA125 alone, the combination of CA125, HE4, FAR, SII, and PNI showed a slight gain in sensitivity (83.91%), negative predictive value (83.91%), accuracy (85.88%), and a decrease in negative likelihood ratio (0.180%). Higher preoperative CA125, HE4, SII, and FAR levels, and lower PNI levels predicted a higher probability of advanced OC progression and lymph node metastasis. FAR has better application value than other inflammation-related markers (PNI and SII). This study suggests that preoperative serum SII, PNI, and FAR may be clinically valuable markers in patients with OC. FAR has better application value than other inflammation-related markers (PNI and SII). As we delve deeper into the inflammatory mechanisms associated with tumors, we may discover more effective combinations of tumor and inflammatory biomarkers.

The value of serum HE4 and CA125 levels for monitoring the recurrence and risk stratification of endometrial endometrioid carcinoma

To evaluate the role of serum human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) levels for predicting and monitoring the recurrence of endometrial endometrioid carcinoma (EEC) and assessing preoperative risk stratification in EEC patients. A total of 434 EEC patients were selected for this retrospective study between May 2011 and August 2018. Serum HE4 and CA125 levels were analyzed before the initial treatment, at the first postoperative follow-up, and at recurrence or the last follow-up. Patients were risk stratified according to the European Society for Medical Oncology (ESMO), European Society for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) guideline. We compared the ability of these biomarkers for prediction and monitoring by performing receiver operating characteristic curve analysis and identified optimal cut-off values by determining the Youden index. Kaplan-Meier analyses were also performed to determine prognostic value. Preoperative serum HE4 was identified as a significant predictor for the recurrence of EEC (p = 0.014). Preoperative serum HE4 and CA125 levels were related to depth of myometrial invasion, lymph node status and FIGO stage. Serum HE4 and CA125 levels were both statistically significant markers for monitoring the recurrence of EEC (P = 0.000 for each biomarker). When combined, the two markers showed higher levels of sensitivity and specificity. The two biomarkers were also significant biomarkers for evaluating the risk stratification of patients undergoing lymphadenectomy (P = 0.000 for each biomarker). For premenopausal stage I patients, preoperative serum HE4 and CA125 levels were significant predictors of the need for ovarian preservation (P = 0.000 and P = 0.002, respectively). For premenopausal patients with stage I intramucosal differentiation, preoperative serum levels of HE4 were significant predictors for fertility preservation (P = 0.024). Preoperative serum HE4 level can be used to predict the recurrence of EEC. Postoperative serum HE4 and CA125 levels can be used to monitor the recurrence of EEC and are more sensitive when combined. Preoperative serum levels of CA125 and HE4 levels are of significant value for risk stratification in EEC patients.

Ovarian Cancer Biomarkers in the COVID-19 Era.

Ovarian Cancer (OC) diagnosis is entrusted to CA125 and HE4. Since the latter has been found increased in COVID-19 patients, in this study, we aimed to evaluate the influence of SARS-CoV-2 infection on OC biomarkers. HE4 values above the cut-off were observed in 65% of OC patients and in 48% of SARS-CoV-2-positive patients (not oncologic patients), whereas CA125 values above the cut-off were observed in 71% of OC patients and in 11% of SARS-CoV-2 patients. Hence, by dividing the HE4 levels into quartiles, we can state that altered levels of HE4 in COVID-19 patients were mostly detectable in quartile I (151-300 pmol/L), while altered levels in OC patients were mostly clustered in quartile III (>600, pmol/L). In light of these observations, in order to better discriminate women with ovarian cancer versus those with COVID-19, we established a possible HE4 cut-off of 328 pmol/L by means of a ROC curve. These results demonstrate that the reliability of HE4 as a biomarker in ovarian cancer remains unchanged, despite COVID-19 interference; moreover, it is important for a proper diagnosis that whether the patient has a recent history of SARS-CoV-2 infection is determined.

Copenhagen index (CPH-I) is more favorable than CA125, HE4, and riskof ovarian malignancy algorithm (ROMA): Nomogram prediction models with clinical-ultrasonographic feature for diagnosing ovarian neoplasms.

We aimed to analyze the benign and malignant identification efficiency of CA125, HE4, risk of ovarian malignancy algorithm (ROMA), Copenhagen Index (CPH-I) in ovarian neoplasms and establish a nomogram to improve the preoperative evaluation value of ovarian neoplasms. A total of 3,042 patients with ovarian neoplasms were retrospectively classified according to postoperative pathological diagnosis [benign, n = 2389; epithelial ovarian cancer (EOC), n = 653]. The patients were randomly divided into training and test cohorts at a ratio of 7:3. Using CA125, HE4, ROMA, and CPH-I, Receiver operating characteristic (ROC) curves corresponding to different truncation values were calculated and compared, and optimal truncation values were selected. Clinical and imaging risk factors were calculated using univariate regression, and significant variables were selected for multivariate regression analysis combined with ROMA and CPH-I. Nomograms were constructed to predict the occurrence of EOC, and the accuracy was assessed by external validation. When the cutoff value of CA125, HE4, ROMA, and CPH-I was 100 U/ml, 70 pmol/L, 12.5/14.4% (premenopausal/postmenopausal) and 5%, respectively, the AUC was 0.674, 0.721, 0.750 and 0.769, respectively. From univariate regression, the clinical risk factors were older age, menopausal status, higher birth rate, hypertension, and diabetes; imaging risk factors were multilocular tumors, solid nodules, bilateral tumors, larger tumor diameter, and ascites. The AUC of the nomogram containing ROMA and CPH-I was 0.8914 and 0.9114, respectively, which was better than the prediction accuracies of CA125, HE4, ROMA, and CPH-I alone. The nomogram with CPH-I was significantly better than that with ROMA (P < 0.001), and a nomogram decision curve analysis (DCA) containing CPH-I seemed to have better clinical benefits than ROMA. For external validation of this nomogram containing ROMA and CPH-I, the C-indices were 0.889 and 0.900, and the calibration curves were close to 45°, showing good agreement with the predicted values. We conclude that CPH-I and ROMA have higher diagnostic values in the preoperative diagnosis of EOC than other single tumor markers like CA125 or HE4. A nomogram based on CPH-I and ROMA with clinical and ultrasonic indicators had a better diagnostic value, and the CPH-I nomogram had the highest diagnostic efficacy.

Are ROMA and HE4 More Accurate than CA-125, in Predicting of Ovarian Epithelial Carcinoma?

Evaluation of ovarian tumors based on tumor markers could have high clinical importance. In this study, we aimed to assess the predictive value of HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) compared to CA-125 in the Malignancy of ovarian epithelial masses. This cross-sectional study was performed in 2020-2021 including 203 patients. Serum HE4 and CA-125 levels were checked before surgery. According to the pathology report (benign, borderline, or malignant epithelial mass), the predictive values of the three markers were evaluated. About 146 cases were benign; 14 cases were borderline and 43 cases were malignant. Most patients (69.8%) in the malignant group were in stage 3. Significantly higher levels of all three markers (CA-125, HE4, and ROMA) were found in patients with malignant tumors compared to benign or borderline tumors (P < 0.001 for all). The sensitivity of CA-125 was the highest (90.7%) in pre- and post-menopausal patients but the specificity of HE4 and ROMA were higher than CA-125 (98.1% and 97.5%, respectively, versus 86.9% for CA-125). In post-menopausal patients, both sensitivities of HE4 and ROMA were 90.5% and the specificity and sensitivity of CA-125 were the highest (95.2% and 100%). In premenopausal patients, the sensitivity of ROMA (90.9%) and the specificity of HE4 (100%) were the highest. HE4 and ROMA are not necessary for postmenopausal patients in low-resource areas and a check of serum CA-125 will be enough. The higher-cost, ROMA, and HE4 checks are recommended in premenopausal people because they are more sensitive.

Predicting value of HE4 and CA125 markers for optimal cytoreductive surgery in ovarian cancer patients.

We conducted a cross-sectional study to evaluate the role of serum levels of CA125 and HE4 in predicting optimal cytoreductive surgery. Eligible women who had been diagnosed with ovarian cancer based on both clinical and imaging criteria were enrolled in this study. Serum levels of CA 125 and HE4 were checked before surgery and all patients underwent complete surgical staging. After completion of the pathological evaluation, data were entered in SPSS version 23. One hundred and ten individuals were enrolled in our study. We divided cases between two groups: stage I to Ш b and stage Шc to IV. Serum level of HE4 >170 pmol/L can predict optimal cytoreductive surgery before operation. (sensitivity:80% and specificity 70%) and serum level of CA 125 > 320 UI/mL can predict optimal cytoreductive surgery before operation. (sensitivity:80% and specificity 70%). Our data demonstrated a negative predictive value of about 80% for both HE4 and CA125. Based on these cut-off, unnecessary surgery can be avoided in many cases, however, it is unwise to ignore clinical performance and radiological findings. Nevertheless, we can say the evaluation of tumor markers is feasible and helpful in predicting optimal surgery.

Diagnostic significance of tumor markers CA125 and HE4 in suspected ovarian cancer

In developed countries, ovarian cancer ranks third in prevalence among malignant diseases of the female genital area; the peak incidence occurs at the age of 55-58 years. An increased risk of ovarian cancer is observed in women with early onset of menstruation and late menopause; women whose first pregnancy occurred at the age of under 19 and over 35 are also at risk. The use of hormonal contraceptives can almost halve the risk of this malignant process. Due to the absence of severe clinical symptoms in every second case, this pathology is detected already at stages III-IV, which explains the rather low survival rate. With timely diagnosis, relapse can be avoided in 73-76% of cases due to the effects achieved in the conduct of chemotherapy. CA125 and HE4 are among the tumor markers of choice, the level of which is checked for suspected ovarian cancer. To assess the risk of the process malignancy, the ROMA index is used. This index represents a mathematical model, the calculation of which takes into account the absolute values of CA125 and HE4, as well as the menopausal status of awoman. Determining the concentration of tumor markers in dynamics is also used to assess the effectiveness of the treatment. At the same time, it should be noted that an increase in the content of tumor markers does not always indicate the presence of a malignant process; this picture can be observed with endometriosis, polycystic ovary syndrome, and neoplasms affecting the peritoneum, pleura, pancreas, and liver.

New Analytical Approach for the Alignment of Different HE4 Automated Immunometric Systems: An Italian Multicentric Study.

Human epididymal secretory protein 4 (HE4) elevation has been studied as a crucial biomarker for malignant gynecological cancer, such us ovarian cancer (OC). However, there are conflicting reports regarding the optimal HE4 cut-off. Thus, the goal of this study was to develop an analytical approach to harmonize HE4 values obtained with different laboratory resources. To this regard, six highly qualified Italian laboratories, using different analytical platforms (Abbott Alinity I, Fujirebio Lumipulse G1200 and G600, Roche Cobas 601 and Abbott Architett), have joined this project. In the first step of our study, a common reference calibration curve (designed through progressive HE4 dilutions) was tested by all members attending the workshop. This first evaluation underlined the presence of analytical bias in different devices. Next, following bias correction, we started to analyze biomarkers values collected in a common database (1509 patients). A two-sided p-value < 0.05 was considered statistically significant. In post-menopausal women stratified between those with malignant gynecological diseases vs. non-malignant gynecological diseases and healthy women, dichotomous HE4 showed a significantly better accuracy than dichotomous Ca125 (AUC 0.81 vs. 0.74, p = 0.001 for age ≤ 60; AUC 0.78 vs. 0.72, p = 0.024 for age > 60). Still, in post-menopausal status, similar results were confirmed in patients with malignant gynecological diseases vs. patients with benign gynecological diseases, both under and over 60 years (AUC 0.79 vs. 0.73, p = 0.006; AUC 0.76 vs. 0.71, p = 0.036, respectively). Interestingly, in pre-menopausal status women over 40 years, HE4 showed a higher accuracy than Ca125 (AUC 0.73 vs. 0.66, p = 0.027), thus opening new perspective for the clinical management of fertile patients with malignant neoplasms, such as ovarian cancer. In summary, this model hinted at a new approach for identifying the optimal cut-off to align data detected with different HE4 diagnostic tools.

Value of serum miR-21, HE4 and CA125 in surveillance for postoperative recurrent or metastatic ovarian cancer.

Objectives:To study the value of serum miR21, human epididymal secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the surveillance for postoperative recurrent or metastatic ovarian cancer.Methods:A total of 169 patients diagnosed with ovarian conditions in Luanzhou Hospital of Traditional Chinese Medicine during January 2016 and March 2019 were divided into a benign lesion (BL) group and an ovarian cancer (OC) group by pathological findings and assigned to a good prognosis (GP) group and a poor prognosis (PP) group according to the follow-up results. A real-time fluorescence quantitative PCR (RT-fqPCR) system was utilized to detect the serum level of miR-21; an enzyme-linked immunosorbent assay (ELISA) was conducted to determine the serum level of HE4; electrochemiluminescence (ECL)-based imaging analysis was performed to measure serum CA125. A receiver operating characteristic (ROC) curve was depicted to analyze the predictive value of serum miR-21, HE4, and CA125 for poor postoperative prognosis in patients with ovarian cancer.Results:Compared with the control group, the BL and OC groups had substantially elevated expression of miR-21, HE4, and CA125 in serum, and the serum levels of miR-21, HE4, and CA125 in the OC group were significantly higher than in the BL group. In the OC group, the serum levels of miR-21, HE4, and CA125 were independent of age and pathological patterns and associated with the clinical staging, degree of transformation and lymphatic metastasis of ovarian cancer; after laparoscopic ovarian tumorectomy, the serum levels of miR-21, HE4, and CA125 were markedly reduced in comparison with the preoperative levels. Compared with the GP group, the PP group experienced a dramatic increase in serum miR-21, HE4, and CA125 expression. The ROC curve showed that the detection of miR-21, HE4, and CA125 was a highly sensitive and specific method to predict the poor prognosis in ovarian cancer; a patient with ovarian cancer was at high risk of a poor prognosis when the serum levels of miR-21, HE4, and CA125 exceeded 1.536, 157.004 pmol/L and 175.243 kU/L, respectively, in which case early intervention should be made to prevent recurrent or metastatic ovarian cancer.Conclusion:Elevated expression of miR-21, HE4, and CA125 in serum is closely associated with the disease status of ovarian cancer. Therefore, the simultaneous detection of these tumor markers has some diagnostic value for postoperative recurrence and metastasis of ovarian cancer.

Acupuncture-exacerbated Pyoderma Gangrenosum Associated With IgG Multiple Myeloma

Introduction. PG is an uncommon, noninfectious neutrophilic dermatosis. Very few cases of bullous PG as the first manifestation of IgG myeloma have been reported. HE4, a novel marker for human cancers, may be a promising marker of bone destruction and disease progression in patients with hematologic malignancies and PG lesions. Case Report. The authors report a case of a 49-year-old female who presented with painful patches located on the lower extremities for the past 5 months, and then had lesions that rapidly progressed to necrotic ulcers after unregulated acupuncture therapy. During the treatment procedure, underlying IgG κ-type myeloma was diagnosed. After the diagnosis was confirmed, the patient underwent chemotherapy, and the lesions started to heal and gradually showed scarring. The current report also discusses the potential value of HE4 as applied to malignancies that present with PG and bone destruction. Conclusions. Once the diagnosis of the underlying systemic disease is confirmed, patients with PG should simultaneously receive aggressive treatment for the primary disease. More emphasis should be put on HE4 regarding the progression of monoclonal gammopathy-related PG with bone destruction to provide new ideas to understand the pathogenesis of this disease.

Relation of a novel fibrosis marker and post-myocardial infarction left ventricular ejection fraction in revascularized patients.

Aim: To investigate the relationship between post-myocardial infarction (MI)left ventricular ejection fraction (LVEF) and fibrosis marker HE-4 in primarily revascularized patients with ST-segment elevation MI (STEMI). Patients & methods: In 94 consecutive STEMI patients (median age 57 [IQR: 50-69] years; 77.7% male), HE-4 values were measured at hospital admission and 4days after STEMI. Transthoracic echocardiography was performed 4days after STEMI (median 5days [interquartile range: 4-6]). Results: HE-4 levels 4days after STEMI were significantly higher in the low ejection fraction group (30.1 [26.0-46.5] pmol/l vs 48.5 [32.5-85.9] pmol/l, p=0.004). In the multivariable analysis, HE-4 values (odds ratio: 1.029, 95% CI: 1.012-1.046, p=0.001), troponin I levels, anterior MIand diabetes mellitus were independent predictors of low LVEF after STEMI. A negative correlation existed between ΔHE-4 levels and LVEF (r: -0.337, p=0.001). Receiver operating characteristic analysis indicated 34.01pmol/l HE-4 at4days after STEMI identified patients with low LVEF (AUC=0.707; 95% CI: 0.601-0.813; p=0.001). Conclusion: In revascularized STEMI patients, high HE-4 levels are associated with decreased LVEF. HE-4 may represent a diagnostic marker and treatment target for patients with heart failure or left ventricular systolic dysfunction after STEMI.

Prospective Analysis of Serum HE4 as an Independent Prognostic Factor in Non Small Cell Lung Cancer

Abstract Background HE4 is expressed in most lung adenocarcinomas and in a significant number of squamous, small cell and large cell carcinomas of the lung, suggesting that it could be used as a diagnostic and/or prognostic factor to refine the standard pathologic analysis. Methodology Data was collected prospectively in the form of blood sample withdrawn from patients with NSCLC confirmed with pathology presented to bronchogenic clinic in Oncology department of Ain Shams University in pretreatment state &amp; from healthy controls with matched age &amp; sex. The Human HE4 (Epididymal Protein 4) was measured in serum samples using Enzyme linked immunosorbent assay [ELISA], the assay was performed using Human HE4 9Epididymal protein 4) ELISA kit, cat no: EH0365 (Fine Test, Wuhan Fine Biotech Co., China). Results 77 patients with NSCLC cases &amp; 30 healthy controls were enrolled in the study. Serum HE4 showed to have to a diagnostic tendency were its value in NSCLC cases was from 42 to 130 pmol/l (median= 72pmol/l). but in controls its value was from 10 to 67 pmol/l (median = 35 pmol/l), which was highly statistically significant (P = 0.001). The cut off value of serum HE4 was 60 pmol/l with sensitivity 77% &amp; specificity 96% (95% CI 0.9-1). Serum HE4 showed to be a poor prognostic marker to OS with statistically significant difference were those with pretreatment serum HE4&amp;lt; 72 pmol/l mean survival time 17.6 months in comparison to the group with pretreatment serum HE4 &amp;gt; 72pmol/l mean survival time 13.2 months (p = 0.02). Conclusion There is a negative correlation between Serum HE4 in NSCLC &amp; overall survival, the highest the serum level the shortest the survival. This result can present serum HE4 as a novel prognostic &amp; probably diagnostic marker for NSCLC.

Using HE4, RMI, ROMA and CPH-I in the differential diagnosis of adnexal masses

Objectives: In order to improve the early diagnosis of ovarian cancer (OC), we evaluated human epididymis secretory protein 4 (HE4), the risk of malignancy index (RMI), the risk of ovarian malignancy algorithm (ROMA), and the Copenhagen Index (CPH-I) in their ability to predict the risk of adnexal masses being malignant, and in discriminating between serous and mucinous ovarian tumors. Methods: A study consisting of 509 patients who were diagnosed with benign, borderline, and malignant adnexal tumors was conducted. We analyzed the values of HE4, RMI, ROMA, and CPH-I. In addition, CA125, CEA, CA125/CEA ratio, CA199, and CA125/CA199 ratio were also assessed to determine their predictive values to diagnoses serous or mucinous ovarian tumors. Results: To differentiate between benign and borderline ovarian tumors, we evaluated RMI and CPH-I scores which showed high AUC (0.7593, and 0.7128, respectively), but neither of them showed both high sensitivity and specificity. When discriminating benign and malignant tumors, RMI and CPH-I performed the best for premenopausal women; whereas ROMA and HE4 performed the best for postmenopausal women. Patients with values above the cutoff for CA125 (&gt; 328.3 U/mL), CA125/CEA (&gt; 82.26), and CA125/CA199 (&gt; 5.633), were more likely to be diagnosed with serous carcinoma. Whereas those with higher values for CEA (&gt; 3.7 μμg/L) and CA199 (&gt; 27.81 ng/mL) were more likely to have a mucinous carcinoma. Conclusion: RMI and CPH-I for premenopausal women, ROMA and RMI for postmenopausal women were reliable indicators to differentiate between women with benign versus malignant tumors. In addition, the ratios CA125/CEA and CA125/CA199 could be used to distinguish serous from mucinous ovarian carcinomas.

Prognostic and predictive value of combined HE-4 and CA-125 biomarkers during chemotherapy in patients with epithelial ovarian cancer.

At present there is no predictive value univocally associated with the success of chemotherapy. Biomarkers produced by ovarian cancer (HE4 and Ca125) could have a good prognostic significance. The aim of this study is to prove the ability of biomarkers to identify patients with the highest risk of non-optimal response during the chemotherapy, and to predict which patients will most likely develop recurrence of disease. We analyzed 78 patients with epithelial ovarian cancers who underwent surgery in the biennium 2016-2017. All the patients underwent chemotherapy after surgery or interval debulking surgery following neoadjuvant therapy. Serum levels of HE4 and Ca125 were measured at diagnosis and at each cycle of chemotherapy. We established the degree of response to the treatment by computed tomography scan, and the patients were followed up (median: 10 months). The parameters of progression-free survival and disease-free survival were related to serum levels of biomarkers. Both CA125 and HE4 values became negative at the fourth cycle in the patients with good response to chemotherapy. HE4 increased earlier than Ca125. The parameters that best correlated with a long progression-free survival were: negativization of the marker after the third cycle of chemotherapy (HE4: odds ratio (OR) 5.5; Ca125: OR 9.1) and biomarker serum levels lower than the mean value in the affected population at the time of diagnosis (HE4: OR 3.4; Ca125: OR 3.7). We can conclude that the monitoring of HE4 and Ca125 during chemotherapy, especially at the third cycle, is recommended, because their variation is a good prognostic factor.

Serum Human Epididymis Protein 4 Level is Associated with Cognitive Function in Patients with Diabetes Mellitus.

BackgroundPrevious studies have reported that patients with diabetes mellitus (DM) have a higher incidence of cognitive decline and an increased risk of developing all types of dementia. The aim was to elucidate the association between serum human epididymal protein 4 and cognitive function in patients with DM.MethodsSerum levels of HE4 were measured in 205 patients with DM. All DM patients were followed up for a median period of 48 months (range=5–49) prospectively. Cox proportional hazard analysis was used to evaluate the predictive value of serum HE4 for predicting cognitive decline (end point).ResultsMultivariate linear regression analysis revealed that serum HE4 was independently associated with MOCA score after adjusting for age, gender, BMI, current smoker, current drinker, admission systolic and diastolic BP, CVD history and laboratory measurements in patients with DM at baseline (Sβ= −0.120; 95% CI, −0.151– −0.069; P<0.001). The multivariate Cox proportional hazard analysis revealed that serum HE4 (HR=2.408, 95% CI 1.669–5.238, P<0.001) was an independent prognostic factor for cognitive decline in these DM patients.ConclusionOur results showed that serum HE4 was significantly and independently associated with cognitive decline and had independent predictive value for cognitive decline in patients with DM. Serum HE4 might enable early recognition of senile dementia among DM patients.

Diagnostic and Prognostic Values of Serum EpCAM, TGM2, and HE4 Levels in Endometrial Cancer.

Objectives: This study aims to investigate the diagnostic and prognostic values of EpCAM, TGM2, and HE4 in endometrial cancer (EC).Methods: In this study, 42 patients diagnosed with EC (EC group), 41 patients diagnosed with myoma (benign group), and 43 healthy women (healthy group), who applied to Affiliated Hospital of Xuzhou Medical University between March 2018 - September 2019 were recruited. Serum EpCAM, TGM2, and IL-33 levels were measured by ELISA, while serum HE4 and CA-125 levels were measured by ECLIA. The serum markers listed above were also measured in 12 paired pre- and post-operative EC patients. The diagnostic and prognostic values of serum markers were analyzed.Results: The serum EpCAM, TGM2, HE4, CA-125, and IL-33 levels were significantly higher in the EC group. The sensitivity and specificity of combined detection of EpCAM and HE4 was 92.86 and 69.05%, which were significantly higher than using a single marker or other combinations. Among these markers, serum HE4 levels were significantly higher in patients with myometrial invasion, metastasis, and lymphovascular invasion (p = 0.006, p = 0.0004, p = 0.0004, respectively). And serum TGM2 levels were significantly decreased in post-operative than that of pre-operative EC patients (p < 0.001).Conclusions: The combination of EpCAM and HE4 showed the highest specificity and sensitivity in the diagnosis of EC. HE4 was successful in the detection of high-risk individuals preoperatively. Additionally, TGM2 might be a prognostic factor for EC.

The differential diagnostic value and clinical significance of serum HE4 in ovarian disease with elevated CA125.

To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients with elevated CA125 levels. The levels and positive expression rate of HE4 were compared between 371 patients with elevated CA125 levels and benign ovarian disease, and 132 patients with epithelial ovarian cancer to determine the diagnostic value of HE4. The level and positive expression rate of HE4 differed significantly between the benign and malignant groups, in that, there was no significant difference in HE4 expression between CA125 low- and high-level groups within the benign ovarian disease group, with levels of HE4 being in the normal range in both groups. However, the positive expression rates and levels of HE4 in the malignant group were significantly different between the serum CA125 low- and high-level groups. ROC curve analysis showed that optimal HE4 cutoff values for increased accuracy in diagnosis were 78.03pmol/L and 119.70pmol/L before and after menopause, respectively. Serum HE4 levels can potentially be used as a marker to differentiate between benign and malignant ovarian disease with elevated serum CA125 levels. The high specificity of HE4 was superior in identifying benign ovarian disease. We recommend increasing the cutoff values of HE4 in premenopausal patients and decreasing the cutoff values in postmenopausal patients for increased accuracy in the differential diagnosis of patients with elevated CA125 levels.