Value Of Human Epididymis Protein Research Articles

The diagnostic value of human epididymis protein 4 and carbohydrate antigen 125 for patients with ovarian neoplasms

Objective Toevaluatethediagnosticvalueofhumanepididymisprotein4（HE4）andcar-bohydrate antigen 1 25 （CA1 25 ）for distinguishing between benign and malignant ovarian neoplasms.Methods 1 1 09 patients with ovarian neoplasms were enrolled in this study,serum concentration of HE4 and CA1 25 was assayed using ELISA technique.And the markers were evaluated for significance separately and in combination. Results 1SerumlevelsofHE4andCA125weresignificantlyhigherinpost-menopausalwomenthanthosein pre-menopausal women（t=8.40,P〈0.05;t=7.02,P〈0.05）.In addition,the more children the patients born,the higher serum levels of these two markers were（F=1 5.36,P〈0.05;F=1 3.00,P〈0.05）.2 Serum HE4 levels were significantly higher in the ovarian cancer patients compared with those seen in patients with benign or borderline tumor（t=1 3.68,P〈0.05;t=1 4.94,P〈0.05）.Serum CA1 25 levels were significantly higher in the ovarian cancer patients compared with those seen in patients with benign or borderline tumor（t=1 4.1 6,P〈0.05;t=1 7.27,P〈0.05）.Morever,it also appared in the ovarian cancer patients with ascites and vascular embolism.Morever,the levels of HE4 were significantly higher in the ovarian cancer with ascites and vascular embolism than without it（t=7.08,P〈0.05;t=4.41,P〈0.05）,the levels of CA125 were signifi-cantly higher in the ovarian cancer with ascites and vascular embolism than without it（t=9.67,P〈0.05;t=4.75,P〈0.05）.3 During follow-up,serum HE4 and CA1 25 levels significantly decreased at 3 months after＆amp;nbsp;operation（t=9.86,P〈0.05;t=5.12,P〈0.05）.4 Receiver operating characteristic curve,ROC）analysis revealed that no difference was observed in AUC values for HE4,CA1 25 and risk of ovarian malignancy algo-rithm（ROMA）.5 Compared to CA1 25 ,HE4 had significantly higher specificity and lower sensitivity.Howev-er,sensitivity were increased when the two markers were combined with each other.However,the sensitivity of combination with two markers was higher than single detection and ROMA,but the specificity was lower in com-bination with two markers than single detection and ROMA.If we divide the ROMA by a woman′s menopausal status,ROMA has a higher sensitivity （73.84%,84.1 9%） and lower specificity （66.06%,66.67%）. Conclusions ThelevelsofCA125hasahighsensitivity,andthelevelsofHE4isahighspecificity.CA125 combined with HE4 can provide a more sensitivity and accurate predictor of ovarian cancer than either alone. Key words: Ovarianneoplasms; Antigens,tumor-associated,carbohydrate

Can HE4 predict platinum response during first-line chemotherapy in ovarian cancer?

Actually, in literature there are not valid tools able to predict the chemotherapy response during first-line ovarian cancer treatment. CA125 and human epididymis protein 4 (HE4) levels of consecutive single-institution patients with epithelial ovarian cancer (EOC) were measured during first-line chemotherapy and until 6 months follow-up. First, patients were divided into two groups according to a temporal criterion: patients treated during 2009 (group A: training group) and patients treated during 2010 (group B: verification group). At sixth months follow-up, patients were sub-classified, within both groups, as platinum resistant or platinum sensitive/intermediate, according to Response Evaluation Criteria in Solid Tumors criteria, and the serum marker courses were further analyzed in each subgroup. Moreover, we performed a logistic regression analysis to choose CA125 and HE4 levels that are best fitted to predict chemoresponse. A total of 76 patients were divided into two groups: group A (n = 42) and group B (n = 34). After 6 months of follow-up, 40 patients were classified as platinum sensitive/intermediate and 36 as platinum resistant. At third chemotherapy cycle, in platinum-resistant patients, HE4 levels were >70 pmol/L in 36 of 36 cases, although in platinum-sensitive/intermediate patients, HE4 levels were >70 pmol/L only in six of 40 cases (sensitivity 100 %, specificity 85 %). Moreover, HE4 reduction of almost 47 % at third chemotherapy cycle reached the sensitivity of 83 % with a specificity of 87 % (positive predictive value = 0.86, negative predictive value = 0.85) in predicting chemoresponse. On the contrary, CA125 values during chemotherapy did not result statistically significant in predicting platinum response. Our findings suggest that HE4 values during first-line chemotherapy could predict chemotherapy response in EOC patients.

Evaluating the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer.

We evaluated the expression and diagnostic value of human epididymis protein 4 (HE4) in small cell lung cancer (SCLC). Serum HE4 level was measured in serum samples from 30 healthy controls and 49 patients with SCLC using enzyme-linked immunosorbent assay. HE4 expression in tumor tissues was analyzed by immunohistochemical staining. The results show that serum HE4 level is significantly higher in SCLC patients than those in healthy controls, which is also the case in tumor tissues where strong intracytoplasmic staining is demonstrable. Using the optimal cutoff value of 84.19 pmol/l, serum HE4 level distinguishes SCLC patients from healthy controls with a sensitivity of 69.4 %, a specificity of 93.3 %, and the area under the receiver operating characteristic curve (AUC) of 0.85. Compared to other well-known tumor markers used in lung cancer diagnosis, HE4 shows the highest sensitivity (69.4 %, 34 of 49) and accuracy (78.5 %, 62 of 79) in diagnosing SCLC, and combinations with other tumor markers further increase the sensitivity and accuracy. These findings suggest that HE4 levels are greatly elevated in sera and tumor tissues of patients with SCLC and serum HE4 is a potential diagnostic marker for patients with SCLC.

Evaluation of tumor marker HE4 assay on the Elecsys 2010 analyzer

Introduction: Whey-acidic protein human epididymis protein 4 (HE4) is a new promising biomarker for epithelial ovarian cancer. The measured HE4 values may depend on the testing procedure used. The aim of this study was to evaluate theMethods: We evaluated a HE4 method on Elecsys 2010 analyzer. The method for quantitative determination of HE4 is direct, competitive chemiluminescent immunoassay. For quality control we use Elecsys PreciControl HE4 1 and 2. HE4 was measure on sera obtained from 56 women ( 20 healthy and 36 with epithelial ovarian cancer).Results: The Roche HE4 assays showed a good linearity (r=0.99) and precision (intrassayed total CV<5%). The median HE4 serum concentrations was significantly higher among EOC patients than healthy females (p<0,05). Elevated levels HE4 were found in 78 % patients with epithelial ovarian cancer.Conclusions: The presented results of the analytical evaluation methods for the determination of HE4 on the Elecsys 2010 analyzer showed an acceptable accuracy and precision.

Diagnostic value of serum HE4 in endometrial cancer: a meta-analysis.

BackgroundEndometrial cancer (EC) is a common female malignant cancer. The age of incidence has become younger than before. If the diagnosis is during stage I, then the survival rate is about 90%. To date, there are no specific tumor markers for endometrial cancer. We usually use serum CA125 to help in diagnosing it. However, a serum biomarker CA125 greater than 35 U/ml is not useful in diagnosing EC at an early stage. Now, human epididymis protein 4 (HE4) has been intensively studied, and has been described as a new marker for ovarian cancer. The goal of this study was to evaluate the clinical value of serum HE4 in the diagnosis of endometrial cancer by meta-analysis.MethodsWe used MEDLINE, EMBASE, Cochrane Library and CBM databases to search the literature. The meta-analysis was performed by using Meta-Disc 1.4 software.ResultsAll data we obtained showed that the major advantage of HE4 lies in its specificity in endometrial cancer diagnosis. Its sensitivity in serum was not as high as expected. But this evidence is not enough.ConclusionsAdditional studies, particularly to evaluate HE4’s capability in identifying EC at an early stage, will be needed.

Clinical value of serum human epididymis protein 4 assay in the diagnosis of ovarian cancer: a meta-analysis

ObjectiveHuman epididymis protein 4 (HE4) has been approved for diagnosing ovarian cancer. The goal of this meta-analysis was to evaluate the clinical value of the serum HE4 in the diagnosis of ovarian cancer.MethodsThe PubMed and Embase databases were searched to identify suitable studies. The sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) of HE4 for the diagnosis of ovarian cancer were commonly used as bivariates. Summary receiver operating characteristic curves were used to summarize overall test performances. Meta-Disc 1.4 software was used to analyze the data.ResultsA total of 6,269 patients from 31 trials were subjected to meta-analysis. The summary estimates of HE4 for ovarian cancer diagnosis were as follows: SEN 0.73 (95% confidence interval [CI] 0.71–0.75); SPE 0.89 (95% CI 0.88–0.90); PLR 7.30 (95% CI 5.42–9.84); and NLR 0.15 (95% CI 0.10–0.23). SEN 0.74 (95% CI 0.72–0.76); SPE 0.89 (95% CI 0.88–0.90); PLR 7.35 (95% CI 5.55–9.73); NLR 0.14 (95% CI 0.09–0.21).ConclusionOur study demonstrates that the sensitivity and specificity of HE4 was higher than that of cancer antigen 125. The results indicated that HE4 could be a useful tumor marker for ovarian cancer diagnosis. However, the results of this meta-analysis should be interpreted with caution, due to the heterogeneity among study designs. Further study should pay more attention to the possibility that HE4 can be a marker for monitoring recurrence of ovarian cancer.

Diagnostic Value of Human Epididymis Protein 4 Compared with Mesothelin for Ovarian Cancer: a Systematic Review and Meta-analysis

Ovarian cancer is the leading cause of death among gynecologic cancers because of the lack of effective early detection methods. Accuracies of the human epididymis protein 4 (HE4) and mesothelin in detecting ovarian cancer have never been systematically assessed. The current systematic review aimed to tackle this issue. MEDLINE, EMBASE, and Cochrane databases were searched (September 1995-November 2011) for studies on the diagnostic performances of HE4 and mesothelin in differentiating ovarian cancer from other benign gynecologic diseases. QUADAS items were used to evaluate the qualities of the studies. Meta-DiSc software was used to handle data from the included studies and to examine heterogeneity. All included studies for diagnostic performance were combined with sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratios (DORs) with 95% confidence intervals (CIs), summary receiver operating characteristic (SROC) curves, and areas under the SROC curves (AUC). A total of 18 studies and 3,865 patients were eligible for the final analysis. The pooled sensitivity estimates for HE4 (74.4%) were significantly higher than those for mesothelin (49.3%). The pooled specificity estimates for mesothelin (94.5%) were higher than those for HE4 (85.8%). The pooled DOR estimates for HE4 (26.22) were higher than those for mesothelin (24.01). The SROC curve for HE4 showed better diagnostic accuracy than that for mesothelin. The PLR and NLR of HE4 were 6.33 (95% CI: 3.58 to 11.18) and 0.27 (95% CI: 0.21 to 0.34), respectively. The PLR and NLR for mesothelin were 11.0 (95% CI: 6.21 to 19.59) and 0.51 (95% CI: 0.42 to 0.62), respectively. The combination of the two tumor markers or their combination with CA-125 increased sensitivity and specificity to different extents. The diagnostic accuracy of HE4 in differentiating ovarian cancer from other benign gynecologic diseases is better than that of soluble mesothelin-related protein. Combinations of two or more tumor markers show more sensitivity and specificity.

Highlights of This Issue

In the United States, primary care physicians play a central role in implementing cancer screening guidelines because many cancer screens require a referral to a specialist. Yabroff and colleagues assessed primary care physicians' use of system strategies in cancer screening, including screening reminders, screening rate performance reports, and implementation of practice guidelines. They found that only 10% of primary care physicians in the United States used systems strategies to support breast, cervical, and colorectal cancer screening. This is the case despite extensive evidence on the effectiveness of these strategies to improve patient care. This report highlights the need for more primary care practices to implement systems strategies to improve the use and quality of cancer screening.The Risk for Ovarian Malignancy Algorithm (ROMA) is a tool that uses serum levels of human epididymis protein 4 (HE4) and CA125 to determine the risk of epithelial ovarian cancer (EOC) in patients with a pelvic mass. In this study, Bandiera and colleagues analyzed the diagnostic and prognostic value of HE4 and CA125 alone or combination (ROMA) to evaluate EOC risks. In both pre- and postmenopausal women, the high specificity of HE4 helped discriminate benign cysts from EOC, and the high sensitivity of CA125 was important for detecting EOC. Elevated HE4 and ROMA were both independent prognostic factors for shorter overall survival. Future multicenter studies will be necessary for further assessment of HE4, CA125, and ROMA to monitor EOC.Although solar UV radiation is a risk factor for cataract formation, the major health benefit of UV radiation exposure is the production of vitamin D, which is implicated in protection against several cancers. In this population-based case–control study, Lurie and colleagues examined the association of ovarian cancer risk with cataract formation as an indicator of high long-term UV radiation exposure. The authors report that a history of cataracts was significantly associated with reduced risk for ovarian cancer, adding indirect evidence to the hypothesis that lifetime vitamin D exposure may be inversely associated with the risk of ovarian cancer.Genetic polymorphisms of Toll-like receptors (TLR) may influence the outcome of Helicobacter pylori infection and play roles in gastric cancer. Zeng and colleagues conducted a population-based study to screen the genetic variants of TLR2 and TLR5 and evaluate their associations with gastric cancer. The authors detected 9 genetic variants within the promoters and exons of TLR2 and TLR5 that either decreased or increased the risk of gastric cancer and/or H. pylori infection. These findings suggest that TLR2 and TLR5 gene variants may influence H. pylori–related gastric cancer carcinogenesis.

Studies on the value of human epididymis protein 4 in patients with ovarian cancer

Objective To evaluate serum human epididymis protein 4 (HE4) as a biomarker for ovarian cancer. Methods HE4 was determined by ELISA in ovarian cancer patients ( n = 82 ) , benign ovarian disease patients ( n = 26 ) and healthy controls ( n = 40) . Results The level of HE4 was significantly higher in ovarian cancer group(46. 6 pmol/L) than that in benign ovarian disease group(31. 5 pmol/L) and healthy control group(24.0 pmol/L) in premenopausal women ( U = 95. 5 and 100.0, P 3. 5% for premenopausal women and > 12. 5% for postmenopausal women. With the progression of ovarian carcinoma, the levels of HE4 as well as the sensitivity were increased. HE4 concentrations were higher in patients with lymph node metastasis than those without metastasis ( U = 34. 0 and 77. 0 in premenopausal and postmenopausal women, P < 0. 01 , respectively). Changes of HE4 concentrations were correlated with tumor response. Elevated levels of HE4 were found in recurrent disease patient, and the levels were decreased while the patients were sensitive to therapy. Conclusion HE4 determination is helpful in the diagnosis and prognosis of ovarian cancer. Key words: Epididymis secretory protein; Tumor markers; biological; Ovarian neoplasms