Serum Human Epididymis Secretory Protein Research Articles

Effects of GnRH Agonist and Dienogest in Combination on HE4 and CA125 Levels in Patients with Adenomyosis and Adenomyoma: A Prospective Cohort Study

Background: The traditional pathology of adenomyosis (AM) suggests that this is a common benign uterine disease. Hysterectomy is the gold standard of care and is viewed as a decisive treatment for AM; however, more conservative treatment approaches are required to maintain fertility. Unfortunately, there are few studies focusing on medical treatments for AM. The objective was to investigate the effect of gonadotropin-releasing hormone agonist (GnRH-a) combined with dienogest on serum human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) levels in patients with AM and adenomyoma. Methods: We addressed our objective using a prospective cohort design. We selected 120 patients treated for AM and adenomyoma from February 2019 to April 2021 in our hospital. The patients were divided into a control group and a study group. The control group was treated with GnRH-a alone, while the study group was treated with GnRH-a combined with dienogest. The curative effect, dysmenorrhea score, dysmenorrhea grade, serum CA125 and HE4 levels, size of the uterine lesions, and incidence of adverse reactions were compared between the two groups. Results: When comparing the two groups, the study group consisted of 43 cases that were significantly effective, 12 effective cases, and five ineffective cases, thus, the effective rate was 91.67%. The control group displayed 23 significantly effective cases, 21 effective cases, and 16 ineffective cases, thus the effective rate for the control group was 73.33%. The curative effect in the study group was higher than in the control group, and the difference was statistically significant (p < 0.05). There was no significant difference in the dysmenorrhea score between the two groups before treatment (p > 0.05). However, after treatment, the dysmenorrhea score in the study group was lower than in the control group 1 month, 3 months, and 6 months after treatment (p < 0.05). There was no significant difference in the levels of serum CA125 and HE4 between the two groups before treatment, but the levels of serum CA125 and HE4 decreased after treatment, and the levels of serum CA125 and HE4 in the study group were lower than in the control group. There was no significant difference in the size of the uterine lesions between the two groups before treatment (p > 0.05). After treatment, the size of the uterine lesions in the study group was smaller than in the control group (p < 0.05). There was no statistical difference in the incidence of adverse reactions between the study group and the control group. Conclusions: GnRH-a combined with dienogest was effective treatment than the single GnRH-a treatment in patients with AM and adenomyoma as evidenced by decreased serum CA125 and HE4 levels, menstrual volume, and dysmenorrhea. The combined treatment could more effectively alleviate the clinical symptoms, reduce the focus volume, and improve the treatment efficiency. For patients with larger adenomyomas requiring conservative treatment, GnRH-a combined with dienogest is a promising therapeutic option.

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.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.

Lung cancer is the most common cause of malignant pleural effusion (MPE). Serum human epididymis secretory protein 4 (HE4) is a useful diagnostic marker for lung cancer. This study aimed to evaluate the diagnostic accuracy of pleural fluid HE4 for MPE. A prospective, double-blind diagnostic test accuracy study. Patients with undiagnosed pleural effusion were enrolled in two cohorts (Hohhot and Changshu). Electrochemiluminescence immunoassay was used to detect pleural fluid HE4. The diagnostic accuracy of HE4 was evaluated by a receiver operating characteristic (ROC) curve, and the net benefit of HE4 was assessed by a decision curve analysis (DCA). A total of 66 MPEs and 86 benign pleural effusions (BPEs) were enrolled in the Hohhot cohort. In the Changshu cohort, 26 MPEs and 32 BPEs were enrolled. In both cohorts, MPEs had significantly higher pleural fluid HE4 than BPEs. The area under the ROC curve (AUC) of HE4 was 0.73 (95% CI: 0.64-0.81) in the Hohhot cohort and 0.79 (95% CI: 0.67-0.91) in the Changshu cohort. At a threshold of 1300 pmol/L, HE4 had sensitivities of 0.44 (95% CI: 0.33-0.56) in the Hohhot cohort and 0.54 (95% CI: 0.35-0.73) in the Changshu cohort. The corresponding specificities were 0.90 (95% CI: 0.83-0.95) in the Hohhot cohort and 0.94 (95% CI: 0.84-1.00) in the Changshu cohort. In subgroup analyses, HE4 had an AUC (95% CI) of 0.78 (0.71-0.85) in exudates and an AUC of 0.69 (0.57-0.81) in patients with negative effusion cytology. The DCA revealed that HE4 determination had a net benefit in both cohorts. Pleural fluid HE4 has moderate diagnostic accuracy for MPE and has net benefit in pleural effusion patients with unknown etiology.

Serum human epididymis secretory protein 4 correlates with sepsis-associated acute respiratory distress syndrome and 28-day mortality in critically ill patients.

Acute respiratory distress syndrome (ARDS) is a severe disease with high mortality, and its primary cause is sepsis. The aim of this study was to detect and evaluate the role of Human epididymis protein 4 (HE4) in sepsis-related ARDS. One hundred and twenty-three critically ill sepsis patients with/without ARDS and 102 healthy controls were enrolled in this study. Blood samples were collected upon admission for quantitative testing of HE4 by chemiluminescent microparticle immunoassay (CMIA). ROC curve analysis and Spearman's correlation analysis were conducted to determine the diagnostic and prognostic value of HE4. Compared with controls, the serum HE4 concentrations of sepsis patients were elevated, and levels in sepsis patients with ARDS were significantly higher (all p < 0.0001). Moreover, HE4 concentrations were strongly correlated with the clinical severity characteristics of sepsis patients, and ROC curve suggested that the AUC of HE4 applied to discriminate sepsis-ARDS patients from sepsis patients was 0.903. HE4 was also found to be a prognostic biomarker of clinical severity and 28-day mortality among critically ill sepsis patients. Logistic regression analysis showed that HE4 was an independent factor for diagnosis of ARDS. Meanwhile, ROC curve analysis showed that the cut-off value of serum HE4 to discriminate 28-day mortality from sepsis patients (AUC: 0.782) was 646.5pmol/L. The concentration of serum HE4 in patients with sepsis-related ARDS was markedly increased and was significantly correlated with mortality, which suggests that serum HE4 could be a promising diagnostic and prognostic biomarker for ARDS in sepsis patients.

Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level: a prospective cross-sectional study in healthy Chinese people.

Background:Human epididymis secretory protein 4 (HE4) is a new ovarian cancer biomarker. The factors influencing HE4 levels are not clear, and the reference data in China are limited. Here, we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.Methods:A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing, China. The serum levels of HE4 and cancer antigen 125 (CA125) were measured by enzyme-linked immunosorbent assay. The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age, menopausal status, and levels of HE4 or CA125. Confidence intervals (5%–95%) were determined for reference ranges in different populations.Results:There was a statistically significant difference in median HE4 levels between the post-menopausal (n = 2168) and pre-menopausal groups (n = 325) (36.46 vs. 24.04 pmol/L, Z = −14.41, P < 0.001). HE4 increased significantly with age in the post-menopausal groups (H = 408.18, P < 0.001) but not in the pre-menopausal subjects (Z = −0.43, P = 0.67). The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women, 78.17 pmol/L for post-menopausal women, and 73.3 pmol/L for all women. In the post-menopausal population, the HE4 reference ranges were 13.15 to 47.31, 14.31 to 58.04, 17.06 to 73.51, 24.50 to 115.25, and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade. The CA125 level was affected mainly by menopausal status and not age.Conclusions:Menopausal status and age were both important factors influencing the level of HE4, and age affected HE4 levels mainly in post-menopausal women. The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age.

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.

Measuring serum human epididymis secretory protein autoantibody as an early biomarker of lung cancer.

BackgroundLung cancer (LC) is one of the most common types of malignant tumors and is the most prominent cause of tumor-related death worldwide. LC is a heterogeneous disease caused by somatic cell mutations and dysregulation in several signaling pathways. Understanding these pathways provides the basis for detecting LC. LC screening and diagnosis in current clinic still rely on computed tomography (CT), but its high false positive rates and cost may prevent it from being a routine screening method. Therefore, the discovery of new non-invasive and more valuable biomarkers may present an improved diagnostic approach for LC, and potentially provide more useful information for the prognosis and treatment of LC in patients. This study investigated the potential of detecting serum autoantibodies produced against human epididymis secretory protein 4 (HE4) for LC diagnosis in high-risk groups.MethodsSerum samples from 61 patients with LC were included in this study, and another 53 serum samples from healthy donors or benign lung diseases (BLD) patients were collected as the control group. The samples were analyzed with enzyme-linked immunosorbent assays (ELISA).ResultsELISA results showed significantly higher levels of serum autoantibodies against HE4 in samples from LC patients compared to the control group (P<0.001). Analysis of HE4 autoantibodies showed a receiver operating characteristic (ROC) curve indicating 67.21% sensitivity, 96.23% specificity, and an area under the curve (AUC) of 0.848. Levels of HE4 autoantibodies can discriminate early-stage LC patients from the control group with a 54.76% sensitivity.ConclusionsDetecting serum HE4 autoantibody levels may be a potential biomarker in high-risk groups of LC. We present a new method for the diagnosis of LC in the clinic.

Diagnostic accuracy of human epididymis secretory protein 4 for lung cancer: a systematic review and meta-analysis.

Several studies have assessed the diagnostic accuracy of serum human epididymis secretory protein 4 (HE4) for lung cancer, but their results were heterogeneous. The aim of this study was to systematically review the available studies and pool their results using meta-analysis. PubMed, EMBASE and Web of Science databases were searched up to January 1, 2019 to identify studies investigating the diagnostic accuracy of HE4 for lung cancer. We assessed the quality of eligible studies with the revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The overall diagnostic sensitivity, specificity, positive and negative likelihood ratios were pooled using a bivariate model. Deeks's test was applied to detect the degree of publication bias. A total of 16 studies with 18 cohorts (1,756 lung cancers and 1,446 controls) were included. HE4 had a pooled sensitivity of 0.65 (95% CI: 0.54-0.75), specificity of 0.88 (95% CI: 0.82-0.92), positive likelihood ration of 5.3 (95% CI: 3.7-7.6) and negative likelihood ratio of 0.40 (95% CI: 0.30-0.52). Patient selection bias and partial verification bias were the major design weaknesses of available studies. No publication bias was observed. HE4 has moderate diagnostic accuracy for lung cancer. Its result should be interpreted in parallel with clinical findings and the results of other conventional tests. Further studies are still needed to rigorously evaluate the diagnostic accuracy of HE4 for lung cancer.

Diagnostic Performance of Serum Human Epididymis Protein 4 (HE4) for Prediction of Malignancy in Ovarian Masses

Background:Early diagnosis of ovarian cancer is essential for long term disease control and mortality reduction. This has been achieved using tumor markers like cancer antigen 125 (CA-125) which is elevated in malignant as well as non-malignant conditions. This dilemma led to efforts towards development of newer markers like serum human epididymis secretory protein E4 (HE4). Present study aimed to evaluate role of HE4 in diagnosing ovarian cancers and comparing it with CA-125. Methods:Serum samples from 67 patients with ovarian cancer, 42 with benign ovarian masses and 26 healthy controls were collected preoperatively and tested for serum HE4 levels and CA-125 levels. Diagnostic performance of both tumor markers (HE4/CA-125) to diagnose malignancy in ovarian masses was calculated and compared to each other. Results:Mean CA-125 and HE4 levels were significantly higher in patients with ovarian cancer than in those with benign disease (p<0.001) or healthy controls (p< 0.001). Serum HE4 levels significantly increased in epithelial ovarian cancers when compared to non-epithelial ovarian cancers (p<0.01). Using benign control as comparison, receiver operating characteristic curve (ROC) was generated to predict a cut-off value for diagnosing malignancy for serum HE4 and CA-125. Compared to CA-125, HE4 had a similar sensitivity (83.6% vs. 85.10%) and higher specificity (100% vs. 90.48%); combination of serum HE4 and CA-125 improved the sensitivity to detect ovarian cancer to 92.54%. Sensitivity of HE4 to detect early stage ovarian cancer was superior to CA-125 (92.61% vs. 63.41%). Conclusion:Serum HE4, a novel tumor marker, discriminated epithelial ovarian cancer from benign ovarian masses. HE4 levels were related to the stage and histological types with the lowest levels in mucinous epithelial ovarian cancer and non-epithelial malignancy. Measuring serum HE4 levels alongwith CA-125 may provide higher accuracy for detecting epithelial ovarian cancer particularly in the early stages.

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.

Value of serum human epididymis secretory protein 4 as a marker for differential diagnosis of malignant and benign gynecological diseases of patients in southern China

BackgroundThis study investigated the clinical value of HE4 in distinguishing malignant and benign gynecological diseases of patients in southern China. MethodsPreoperative serum CA125 and HE4 concentrations were tested in samples of women with malignant or benign gynecological diseases using fully automated methods (Abbott ARCHITECT) and validated cutoff values. ResultsFor the discrimination of ovarian cancer from benign gynecological diseases, in premenopausal women, the sensitivity and specificity were 89.8% and 67.5% for CA125, 68.5% and 97.8% for HE4, and 88.9% and 78.6% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 86.6% and 88.9% for CA125, 57.3% and 100% for HE4, and 85.4% and 94.4% for ROMA. For the discrimination of endometrial cancer from benign gynecological diseases, in premenopausal women, the sensitivity and specificity were 20.3% and 67.5% for CA125, 56.8% and 97.8% for HE4, and 74.3% and 78.6% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 17.8% and 88.9% for CA125, 31.5% and 100% for HE4, and 32.9% and 94.4% for ROMA. ConclusionsWe showed that HE4 had better specificity than CA125 in discriminating ovarian cancer, and endometrial cancer from benign gynecological diseases in southern China population.

Value of detection of serum human epididymis secretory protein 4 and carbohydrate antigen 125 in diagnosis of early endometrial cancer of different pathological subtypes.

This study explored the value of detection of human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) from serum in diagnosis of early endometrial cancer of different pathological subtypes and discussed the mechanism of HE4 and CA125 in diagnosis. In this study, enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect HE4 and CA125 from serum in endometrial cancer and control groups. Besides, the concentration of HE4 and CA125 was compared in these two groups, and the expression of CA125 and HE4 and clinicopathological characteristics in patients with endometrial cancer were also analyzed. Compared with the control group, the expression of HE4 was much higher in serum of patients with endometrial cancer, while there was no obvious change in the expression of CA125. The threshold detection value was acquired by receiver operating characteristic analysis method, that is, 141.5 pmol/L and 54.5 U/L, respectively. When comparing the concentration of HE4 in patients with endometrial cancer at the early stage (stage I) with healthy people, the difference therein had statistical significance, but there was no obvious difference in CA125. HE4 and CA125 in diagnosis of endometrial cancer in the stages I and II were found with no statistically significant difference. The difference of HE4 in the stages II and III had statistical significance while the difference of CA125 had no statistical significance. The specificity of both HE4 and CA125 was 95%, and the sensitivity of HE4 to uterine papillary serous carcinomas was higher than that to endometrioid adenocarcinoma. Thus, the serum HE4 is much better than CA125 in detecting the endometrial cancer at an early stage.

The role of novel biomarker HE4 in endometrial cancer: a case control prospective study

The aim of the study was to explore the clinical value of serum human epididymis secretory protein E4 (HE4) and CA125 in endometrial carcinoma. From January 2010 to April 2012, serum specimens were collected from consecutive cases of endometrial carcinoma and from cases of uterus benign disease (control group). The CA125 normal value is considered less than 35U/mL. Two HE4 cutoff are considered: less than 70pmol/L and less than 150pmol/L. The specificity analysis was performed using the Mann-Whitney test for the CA125 and HE4 series. The level of statistical significance is set at p < 0.05. The sensitivity of CA125 in detecting endometrial cancer is 19.8%, whereas the sensitivity of HE4 is 59.4 and 35.6% for 70 and 150pmol/L cutoff, respectively. Thus the specificity of HE4 is 100% (positive predictive value = 100%, negative predictive value = 71.52 and 61.31% considering the two HE4 cutoff, respectively), whereas the CA125 specificity is 62.14% (positive predictive value = 33.9%, negative predictive value = 44.14%) in detection of endometrial cancer. Combining CA125 and HE4, the sensitivity to detect endometrial cancer is 60.4 and 34.6%, at HE4 cutoff of 70 and 150pmol/L, respectively, with a specificity of 100%. HE4 may be a new tool for preoperative evaluation and postoperative surveillance of endometrial cancer patients, with a positive predictive value = 100%. HE4 at cutoff of 70pmol/L yields the best sensitivity and specificity.

Detection of serum human epididymis secretory protein 4 in patients with ovarian cancer using a label-free biosensor based on localized surface plasmon resonance

BackgroundDetection of the human epididymis secretory protein 4 (HE4) biomarker plays an important role in the early diagnosis of ovarian cancer. This study aimed to develop a novel localized surface plasmon resonance (LSPR) biosensor for detecting HE4 in blood samples from patients with ovarian cancer.MethodsSilver nanoparticles were fabricated using a nanosphere lithography method. The anti-HE4 antibody as a probe, which can distinctly recognize HE4, was assembled onto the nanochip surface using an amine coupling method. Detection was based on the shift in the extinction maximum of the LSPR spectrum before and after the HE4-anti-HE4 antibody reaction. These nanobiosensors were applied to detect HE4 in human serum samples and compare them using an enzyme-linked immunosorbent assay.ResultsTests relating to the detection of HE4 demonstrated that the LSPR-based biosensor featured a fast detection speed, good specificity, effective reproducibility, and long-term stability. The linear range for LSPR was between 10 pM and 10,000 pM, with a detection limit of 4 pM. An excellent correlation between LSPR and enzyme-linked immunosorbent assay results was observed in human serum.ConclusionThis study is the first clinical diagnostic application of the LSPR biosensor in ovarian cancer. The LSPR biosensor, a rapid, low-cost, label-free and portable screening tool, can serve as a very effective alternative for the clinical serological diagnosis of ovarian cancer.

Measurement of serum human epididymis secretory protein 4 combined with CA125 assay in differential diagnosis of endometriosis cyst and ovarian benign and malignant tumors

To investigate the value of human epididymis secretory protein 4(HE4) combined with CA125 assay in differential diagnosis of endometriosis cyst and ovarian malignant tumor. The level of HE4 and CA125 were measured by enzyme-linked immunosorbent assay (ELISA) in the serum specimens of 46 cases in endometriosis cyst group, 36 cases in malignant ovarian tumor group, 60 cases in benign ovarian diseases and 50 women in healthy women group. Those results were shown with median level. The normal range were 0-150 pmol/L in HE4 and 0-35 kU/L, which either one was more than the threshold value defined as positive index. The sensitivity of assay was evaluated by receiver operating characteristic (ROC) curve, the relation and value of HE4 or CA125 alone and combination assay in diagnosis of endometriosis was analyzed by Mann-Whitney U test and correlation analysis. (1) HE4: the median levels of HE4 were 52.4, 51.0, 50.0 pmol/L in group of endometriosis, normal control and benign ovarian tumor, which didn't show statistical difference. However, HE4 was 507.5 pmol/L in ovarian cancer group, which was significantly higher than those of 3 groups (P<0.05). (2) CA125: there were significant different in median level of CA125 was observed as 743.0 kU/L in ovarian cancer, 84.9 kU/L in endoemtriosis, 15.4 kU/L in benign ovarian disease, and 11.5 kU/L in healthy women (P<0.05). (3) The single assay: when compared with that in endometriosis group, receiver operating characteristic area under the curve (ROC-AUC) were 0.933 in HE4 alone and 0.821 in CA125 alone assay in ovarian cancer group. The specificity was 95% and the sensitivity was 79.6% and 49.0%. (4) The combination assay: when compared with those in endometriosis group, the ROC-AUC was 0.936, the specificity was 95% and the sensitivity was 81.0% in ovarian cancer. Measurement of HE4 could be used in differential diagnosis of endometriosis cyst. And the combination of HE4 and CA(125) assay could discriminate ovarian endometriosis cysts from ovarian malignant tumors effectively.