Assessment of diagnostic value of human epididymis secretory protein versus CA125 for endometrial cancer / 中华老年医学杂志

Objective To assess the diagnostic value of human epididymis secretory protein (HE4) versus CA125 for endometrial cancer.Methods Serum HE4 and CA125 levels were measured by enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECLI) in 35 patients with endometrial cancer,48 patients with benign endometrial disorders and 40 healthy controls.The best cutoff value,sensitivity and specificity were calculated with pathological results as golden standard.Receiver operating characteristic curves were plotted,and areaunderthecurve (ROC-AUC) was used to compare diagnostic value of HE4 and CA125.Results The median value in HE4 in endometrial cancer were 51.46 pmol/L,which was significantly higher than in the healthy and benign disorder controls (25.65 pmol/L and 27.92 pmol/L).However,CA125 levels did not show statistically significant difference among the 3 groups.The ROC-AUC of HE4 for discriminating endometrial cancer between healthy controls and benign disorder controls were 0.922 and 0.759,respectively,which showed higher diagnostic value than CA125 (ROC-AUC of 0.590 and 0.457,respectively).HE4 had a specificity/sensitivity of 87.5％ /86.1％ for distinguishing healthy controls from endometrial cancer,and 95.5％ /50％ for differential diagnosis with benign disorders.Conclusions Measurement of HE4 can be used as a tumor marker for diagnosis of endometrial cancer.

Clinical value of risk of ovarian malignancy algorithm in risk stratification of ovarian cancer / 中华全科医师杂志

The serum specimens were collected from ovarian cancer (n =100),benign ovarian disease (n =69) and healthy women (n =95).The serum levels of HE4 and CA125 were detected.Risk of ovarian maliqnancy algorithm (ROMA) was calculated.Accuracy of prediction was evaluated by the area under receiver operating characteristic curve (ROC-AUC).And validity of prediction was evaluated by sensitivity and specificity.The results showed that the median level of ROMA algorithm was 83.0％,8.9％ and 8.7％ in ovarian cancer,benign ovarian disease and healthy women groups respectively.The difference were statistically significant (all P ＜ 0.01).Compared with benign ovarian disease group,the ROC-AUC of ROMA algorithm was 0.900 in ovarian cancer group.The sensitivity and specificity were 81.0％ and 92.8％ in ovarian cancer group respectively.Thus ROMA algorithm is a useful parameter in risk stratification for ovarian cancer.The diagnostic accuracy of ROMA algorithm is better than that of HE4 and CA125 in ovarian cancer.

Significance of combined detection of tissue polypeptide antigen and human epididymal secretory protein 4 in the diagnosis and disease monitoring for ovarian epithelial cancer / 中国基层医药

Objective To study the clinical value of combined detection of tissue polypeptide antigen(TPA) and human epididymal secretory protein 4 (HE4) in the diagnosis and disease monitoring for ovarian epithelial cancer.Methods 82 cases with epithelial ovarian cancer were enrolled in ovarian cancer group,93 cases with benign ovarian lesions were selected as the benign ovarian lesions group,100 healthy people were selected as the control group.Serum TPA and HE4 were detected by ELISA.Results TPA-positive rates in the ovarian cancer group,benign ovarian lesions group and control group were 70.7％,8.6％ and 2.0％,respectively.The TPA-positive rate of ovarian cancer group was higher than benign ovarian lesions group and control group (x2 =33.69,82.95,all P ＜ 0.01).But the difference was not statistically significant between the benign ovarian lesions group and the control group(x2 =3.80,P ＞ 0.05).HE4 positive rates of the ovarian cancer group,benign ovarian lesions group and control group were 82.9％,11.8％,3.0％.The HE4 positive rate of ovarian cancer group was higher than benign ovarian lesions group and control group (x2 =36.72,78.33,all P ＜ 0.01).But the difference was not statistically significant between the benign ovarian lesions group and the control group(x2 =3.28,P ＞ 0.05).The sensitivity,specificity and accuracy of TPA in the diagnosis of ovarian cancer were 70.7 ％,95.2％,88.7％.The sensitivity,specificity and accuracy of HE4 in the diagnosis of ovarian cancer were 82.9 ％,97.2％,92.8％.Conclusion TPA and HE4 can improve the accuracy of the diagnosis of ovarian cancer.

A study on diagnostic values of combined detection of serum CA 125,HE4,SMRP for ovarian cancer / 国际检验医学杂志

Objective To evaluate the values of combined detection of carbohydrate antigen 125(CA125) ,human epididymis gene protein 4(HE4) ,soluble mesothelin related peptides(SMRP) in early diagnosis for ovarian cancer and the high-risk factors of ovari-an cancer .Methods 43 patients with malignant ovarian cancer were served as the malignant group ,54 patients with benign ovarian tumors as the benign group ,45 healthy women as the control group .Roche Cobas 6000 Automatic Electrochemiluminescence Immu-noassay Analyzer and enzyme-linked immunosorbent assay (ELISA) were adopted to detect serum CA125 ,HE4 ,SMRP levels . High-risk factors of ovarian cancer was subject to Logistic regression analysis .Results Serum levels of CA125 ,HE4 and SMRP of patients in malignant group were significantly higher than those in the benign group and the control group (P<0 .01) .The sensitivi-ties of CA125 ,HE4 and SMRP detection alone for ovarian cancer diagnosis were 73 .3% ,82 .8% and 70 .8% ,respectively ,while their specificities were 79 .1% ,87 .4% and 83 .3% ,respectively .The sensitivity and specificity of joint detection of CA 125 ,HE4 , SMRP for ovarian cancer diagnosis were 90 .2% and 79 .3% ,respectively .Logistic regression analysis showed that age at menarche younger than 13 years ,menstrual cycle less than 30 d and irregular menstruation were the high-risk factors of ovarian cancer ,with their odds ratio(OR) of 2 .11[95% confidence interval(CI):1 .09-4 .10 ,1 .91(95% CI:1 .21-3 .10) and 1 .57(95% CI:0 .83-2 .94) .Conclusion CA125 detection combined with HE4 or SMRP can markedly improve the diagnostic sensitivity for ovarian cancer .

Meta-analysis of serum HE4 and HE4/CA125 parallel detection for the diagnosis of ovarian cancer / 中华检验医学杂志

Objective To evaluate the diagnostic value of Human Epididymal Protein 4(HE4) and HE4/Cancer Antigen 125 (CA125) parallel detection for ovarian cancer by meta-analysis.Methods The databases,such as Pubmed,Embase and China National Knowledge Infrastructure (CNKI),were employed to search for the studies related to diagnostic value of HE4 and HE4/CA125 parallel detection for ovarian cancer.The screening,data extraction and quality assessment were conducted in accordance with the inclusion and exclusion criteria by two reviewers independently.The software Meta-disc 1.4 was used to perform meta-analysis and draw the forest plots and the Summary Receiver Operating Characteristic (SROC) curves.The AUCs of HE4,HE4/CA125 parallel detection were detected by Z test.The Egger's regression test was applied to evaluate the publication bias by Stata11.0.Results A total of 14 studies with benign control and/or healthy control were included.In the studies with healthy control.The AUCs of HE4,HE4/CA125 parallel detection were 0.9502 ± 0.0137 and 0.9588 ± 0.0113 respectively,but there was no significant difference between them (Z =0.484,P ＞ 0.05) ;In the studies with benign control.The value of cutoff was the most important cause of heterogeneity.The AUCs of HE4,HE4/CA125 parallel detection were 0.9153 ± 0.0095 and 0.9323 ± 0.0082 respectively,but with no significant difference (Z =1.350,P ＞ 0.05).In the subgroup with cut-off value divided by 150 pmoL/L,the AUCs of HE4,HE4/CA125 parallel detection were 0.9032±0.0174 and 0.9267 ±0.0176 respectively,but there was no significant difference between them (Z =0.950,P ＞ 0.05).Conclusions Both HE4 and HE4/CA125 parallel detection had meaningful values for the diagnosis of ovarian cancer.The detection of HE4 had a higher specificity,while the HE4/CA125 parallel detection had a higher sensitivity.But there was no statistical difference between them in diagnosis value of ovarian cancer.

Clinical value of combined detection of serum human epididymal secretory protein E4 and CA125 in the diagnosis of endometrial carcinoma / 中华妇产科杂志

Objective To explore the clinical value of combined detection of serum human epididymal secretory protein E4 (HF4) and CA125 in the diagnosis of endometrial carcinoma.Methods From Jan 2010 to Apr 2011,the serum specimens were collected from124 cases of endometrial carcinoma,97 cases of benign disease of uterus and 109 cases of healthy women.HE4 levels in the serum were detected by ELISA,and CA125 levels in the serum were detected by the electro- ehemiluminescent immunoassay.Those results were shown with median level.Accuracy of the diagnosis was evaluated by the area under the receiver operating characteristic curve ( ROC-AUC ).ResultsThe median levels of HE4 and CA125 were 78.09 pmol/L and 33.43 kU/L in serum of endometrial carcinoma group.The median levels of HE4 and CA125 were 46.37 pmol/L and 18.26 kU/L in serum of benign disease of uterus group.The median levels of HE4 and CA125 were 31.75 pmol/L and 12.64 kU/L in serum of healthy women group.The HE4 and CA125 levels in serum of endometrial carcinoma group were significantly higher than those of benign disease of uterus group or healthy women group ( all P ＜ 0.05 ).Compared with that benign disease of uterus group,the ROC-AUC of HE4 and CA125 in endometrial carcinoma group were 0.913 and 0.801,respectively.When the specificity was 95.0％,the sensitivities of HE4,CA125,and combined detection of HF4 and CA125 in endometrial carcinoma group were 41.1％,22.6％ and 46.0％,respectively.The positive rates of HE4 and CA125 were 31％ (27/86) and 12％ (10/86) in stage Ⅰ - Ⅱ of endometrial carcinoma,while the positive rates were 63％ (24/38) and 47％ (18/38) in stage Ⅲ -Ⅳ of endometrial carcinoma,in which there were significant difference between patients in stage Ⅲ - Ⅳ and stage Ⅰ - Ⅱ (P ＜ 0.01 ).ConclusionsThe combined detection of serum HE4 and CA125 is helpful to the diagnosis of endometrial carcinoma.The sensitivity,specificity and early diagnosis of HE4 are better than that of CA125.The positive rates of HF4 and CA125 in endometrial carcinoma are related to the clinical staging.

A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses

OBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.

Research progress of the relation of HFA and oarian cancer / 国际肿瘤学杂志

Human epididymis gene product 4 (HFA)mRNA highly expressed in oarian cancer tissue and the quantity was associated with the type of the ovarian cancer;The serum HF4 had the same specificity and sensitivity in the early diagnosis of oarian cancer compared with CA125 ,and the HF4 had an advantage over theCA125 in that it was less frequently positive in patients with nonmalignant disease;the combination of HE4 andCA125 yielded higher sensitivity ;The serum tumor marker HFA is an excellent marker for determining responseto treatment and for the detection of early recurrence of disease in patients with epithelial ovarian cancer; HE4 isnot only a serological tumor biomarker but also a target for gene-based therapy 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 / 中华妇产科杂志

Objective 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.Methods 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.Results (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 inovarian 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.Conclusions Measurement of HE4 could be used in differential diagnosis of endometriosis cyst.And the combination of HE4 and CA125 assay could discriminate ovarian endometriosis cysts from ovarian malignant tumors effectively.

The values of serunl human epididymis secretory protein 4 and CA125 assay in the diagnosis of ovarian malignancy / 中华妇产科杂志

Objective To evaluate the value of human epididymis secretory protein 4(HE4)and CAl25 in the diagnosis of ovariall malignancy.Methods HF4 and CA125 in the serum specimens of malignant ovarian tumor group(30 cases),benign ovarian diseases(110 cases;45 benign ovarian tumor,57endometriotic diseases and 8 pelvic inflammation were included) and healthy women group( 137 cases)were assayed double blindly . The levels and the diagnosis efficiency of the HE4 and CA125 were analyzed.Results (1) The median levels of HE4 and CA125 were significantly higher in malignant ovarian tumor group (244 pmoi/L and 601 kU/L respectively) than those of the benign ovarian diseases group( 32 pmol/L and 22 kU/L respectively)and healthy women group (32 pmoi/L and 11 kU/L respectively) (P =0. 000-0. 029). The median levels of CA125 were also higher in endometriotic diseases and pelvic inflammation groups(53 and 41 kU/L respectively) than those of benign ovarian tumor group and healthy women group (12 and 11 kU/L respectively;P = 0. 000-0. 031 ). (2) The positive rate of HE4 was lower than that of CA12s in malignant ovarian tumor group ( P = 0. 036 ). HE4 was negative in benign diseases and healthy women groups. But the positive rates of CA125 were 56. 1% and 5/8 respectively in endometriotic diseases and pelvic inflammation groups and there were significant differences compared with HE4( P =0. 000). (3)The HE4 assay had advantage over the CA125 assay in receiver operating characteristic-area under the curve (ROC-AUC) and sensitivity with a specificity of 100% when ovarian malignancy was compared with controls having benign diseases and healthy women, benign tumor or benign diseases groups respectively. The CA125 assay had advantage over the HE4 assay in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having healthy women group. (4) Combined assay of HE4 and CA125was better than CA125 alone when ovarian malignancy was compared with controls having any group. (5)Combined assay was better than HE4 alone in ROC-AUC and sensitivity with the same specificity when ovarian cancers were compared with controls having benign diseases and healthy women or healthy women groups. And combined assay was lower in the ROC-AUC and the sensitivity with specificity of 100% than HE4 when ovarian cancers were compared with controls having benign tumors or benign diseases groups respectively. (6) The diagnosis efficiency of the HE4 assay at the level 86 pmol/L determined in ROC curve with controls having benign diseases and healthy women group and at the 95% reference level 50 pmol/L of healthy women or 150 pmol/L recommended by the kit respectively was compared. The sensitivity of 50 pmol/L was 73% higher than 150 pmol/L and 86 pmoi/L, while the specificity and positive predictive value were lower ( P = 0. 002, P = 0. 000 ). The specificity, accuracy and positive predictive value of HE4 assay at the set point of 150 pmol/L and 86 pmol/L were 100%, 96% and 96%. The set point of 86 pmol/L had advantage over 150 pmol/L at the sensitivity of diagnosis, 70% and 63% respectively. But the positive predictive value was 95% lower than 150 pmol/L, being 100%. There was no significant difference( P =0. 883, P = 0. 883 ). Conclusions The specificity of HF4 assay is higher than CA125 assay in the diagnosis of ovarian cancer and HE4 combined with CA125 assay can improve the diagnoses. The set point of 150 pmol/L is advantageous for the accurate diagnosis, while the set point of 86 pmol/L is advantageous for the screening of malignant ovarian cancer.