Meta-analysis of Relationship Between Expression Level of Human Epididymis Protein 4 and Lymph Node Metastasis in Endometrial Cancer / 肿瘤防治研究

Objective To evaluate systematically the correlation between the expression level of human epididymis protein 4 (HE4) and lymph node metastasis of endometrial cancer (EC). Methods Computers were used to search for the literatures about the correlation between the expression level of HE4 and lymph node metastasis of EC in PubMed, Cochrane, Web of Science, CBM, CNKI, and Wanfang Database. The search time was from the database establishment to May 2021. Articles were screened in accordance with the inclusion and exclusion criteria, and the quality of literature was evaluated by Newcastle Ottawa scale. Stata12.0 was used to perform meta-analysis, and TSA was used to evaluate the sample size. Results A total of 2736 patients with EC were included in the 25 eligible studies. The results of meta-analysis showed that the expression level of HE4 in the EC-lymph-node metastasis group was significantly higher than that in the non-metastasis group (SMD=1.58, 95%CI: 1.13-2.03), and meta-regression analysis revealed that the results were related to the average age of patients in each study. TSA analysis exhibited that the total sample size of the included studies met the requirements. Conclusion The expression level of HE4 is correlated with lymph node metastasis of EC, and this correlation may be affected by age, body mass index, and other factors. The correlation weakens with the increase in age.

Assessing the diagnostic performance of four ovarian malignancy prediction risk models in differentiating benign and malignant ovarian masses in a tertiary hospital / Philippine Journal of Obstetrics and Gynecology

Introduction@#Ovarian cancer is considered the most lethal gynecologic malignancy because it is difficult to diagnose in its early stages. Ovarian malignancy prediction models may be useful in discriminating between benign and malignant masses, allowing for accurate and timely referral as well as proper therapeutic care@*Objective@#To evaluate the diagnostic performance of the four ovarian prediction models: Risk of Malignancy Index‑4 (RMI‑4), Risk of Ovarian Malignancy Algorithm (ROMA), Copenhagen Index (CPH‑I), and International Ovarian Tumor Analysis (IOTA)‑Assessment of Different NEoplasias in the AdneXa (ADNEX) in identifying malignant and benign ovarian masses@*Materials and Methods@#This was a retrospective, cross‑sectional, analytical diagnostic study in a tertiary hospital between January 2017 and December 2020. Receiver operating characteristic (ROC) curves, area under the curves (AUCs), sensitivities, specificities, positive and negative predictive values, and positive and negative likelihood ratios were used to assess the diagnostic performance of the prediction models.@*Results@#We analyzed a total of 248 patients. One hundred and sixty‑one (65%) had benign tumors, 28 (11%) had borderline, and 59 (24%) had malignant tumors. The AUCs of all models were all above 90%, but when compared to the other models, CPH‑I had the best estimate. RMI‑4 had the highest sensitivity (98.3%) in diagnosing malignancy. For appropriately diagnosing benign disease, the IOTA‑ADNEX model exhibited the highest specificity (92.1%). Overall, RMI‑4 had the lowest diagnostic accuracy (74.6%), whereas IOTA‑ADNEX had the greatest (93.2%).@*Conclusion@#The four malignancy prediction models in this study were all useful tools in discriminating between benign and malignant ovarian tumors. IOTA‑ADNEX, CPH‑I, and ROMA all demonstrated overlapping diagnostic performances indicating that they are equal in that regard. In terms of sensitivity in predicting malignancy, RMI‑4 was the most sensitive. CPH‑I is the predictor with the best overall estimate. Lastly, IOTA‑ADNEX was the most specific, and displayed highest diagnostic accuracy among the four

The power of the Risk of Ovarian Malignancy Algorithm considering menopausal status: a comparison with CA 125 and HE4 / 부인종양

OBJECTIVE: To identify the power of tumor markers for predicting ovarian cancer according to menopausal status. METHODS: The medical records of 876 women with ovarian cysts were retrospectively reviewed. Cancer antigen 125 (CA 125), human epididymis protein 4 (HE4), and Risk of Ovarian Malignancy Algorithm (ROMA) were analyzed. Sensitivity, specificity, and the receiver operating characteristic (ROC) curve analyses of these tumor markers were evaluated. RESULTS: The sensitivity of ROMA was 66.7% and the specificity was 86.8% to detect ovarian malignancy. The patients were divided into 2 groups according to menopausal status: premenopause (n=532, 60.7%) and postmenopause (n=344, 39.3%). For diagnostic accuracy, ROMA was lower than HE4 in premenopausal women (82.7% vs. 91.4%) and lower than CA 125 in postmenopausal women (86.9% vs. 88.7%). The ROC curve analysis revealed that the power of ROMA was not significantly better than that of HE4 in premenopausal women (area under the curve [AUC], 0.731 vs. 0.732, p=0.832), and it was also not significantly better than that of CA 125 in postmenopausal women (AUC, 0.871 vs. 0.888, p=0.440). CONCLUSION: The discrimination power of tumor markers for ovarian cancer was different according to menopausal status. In predicting ovarian malignancy, ROMA was neither superior to HE4 in premenopausal women nor superior to CA 125 in postmenopausal women.

Effect of HE4 and PAX8 gene knockdown on malignant biological behaviors of epithelial ovarian cancer cells treated with TC regimen / 中国肿瘤生物治疗杂志

@#Objective: To investigate the effect of human epididymal protein 4 (HE4) and paired box gene 8 (PAX8) gene knockdown on proliferation, migration, invasion and apoptosis of human epithelial ovarian cancer OVCAR3 cells treated with TC regimen (paclitaxel+carboplatin). Methods: Sequences of single-target siRNA (HE4-siRNA or PAX8-siRNA) and double-target siRNA (HE4+PAX8siRNA) as well as negative siRNAwere respectively designed and synthesized, and then linked with plasmid vector pGCsi-H1 to obtain the recombinant plasmids. The obtained recombinant plasmids were then transfected into human epithelial ovarian cancer OVCAR3 cells, namely HE4-siRNA group, PAX8-siRNA group, HE4+PAX8-siRNA group and siRNA-NC group, respectively. The blank control group was also set up (without any treatment). The cells in above five groups were treated with TC regimen (paclitaxel 3.13 g/ml+carboplatin 2.82 µg/ml), and the changes in proliferation, migration, invasion and apoptosis of the cells were detected by MTT, wound-healing assay, Transwell chamber assay, and flow cytometry, respectively. Results: After knocking down the HE4 and PAX8 genes, compared with siRNA-NC group and blank control group, the proliferation, migration and invasion abilities of OVCAR3 cells in HE4-siRNA group, PAX8-siRNA group and HE4+PAX8-siRNA group significantly decreased (all P<0.01), and the apoptosis rate significantly increased (P<0.01), especially in HE4+PAX8-siRNA group. Conclusion: Knockout of either HE4 or PAX8 can enhance the effect of TC regimen on inhibiting proliferation, migration and invasion as well as promoting apoptosis of epithelial ovarian cancer cells, and the effect of simultaneous down-regulation of HE4 together with PAX8 is better.

Clinical value of HE4,CA125 and ROMA in diagnosis of ovarian epithelial malignant tumor / 中国实用妇科与产科杂志

OBJECTIVE: To investigate the value of HE4,CA125 and ovarian malignant tumor risk prediction models(ROMA)in the diagnosis of ovarian epithelial malignant tumors.METHODS: The clinical and pathological data of 247 patients with ovarian tumors(EOC 139 cases,BOT 18 cases,and benign ovarian tumor 90 cases)and 39 patients with uterine fibroids in Liaoning Tumor Hospital from September 2016 to August 2017 were retrospectively analyzed. The levels of serum CA125 and HE4 were measured before operation. The ROMA values were calculated and the relationship between CA125,HE4,ROMA values and clinical pathological parameters were analyzed. The diagnostic evaluation index was calculated,the receiver operating characteristic(ROC)curve was drawn,and the AUC value was also calculated.RESULTS: The positive rate of HE4 in the ovarian epithelial malignant tumor group was significantly higher than that in other groups before and after menopause,the difference being statistically significant(P0.05).There was no significant statistical difference in the positive rate of ROMA before or after menopause(P>0.05).The sensitivity of CA125 was higher than that of HE4 and ROMA. Specificity of HE4 was higher than that of CA125 and ROMA.Correct diagnosis index of ROMA was higher than that of HE4 and CA125.CONCLUSION: For the diagnosis of ovarian malignant epithelial tumors,the combined detection of serum HE4 and CA125 and ROMA model is superior to the individual detection of HE4 and CA125.

Effect of CEA, CA19-9, CA125, HE4 and menopausal ROMA in the clinical staging of endometrial carcinoma / 国际检验医学杂志

Objective To investigate the effects of carcinoembryonic antigen (CEA), carbohy-drate antigen (CA19-9), carbohy-drate antigen (CA125), human epididymis protein 4 (HE4) And the combined detection of ovarian cancer risk prediction model (ROMA) in the diagnosis and significance of endometrial cancer.Methods From May 2014 to May 2010, 80 patients with endometrial cancer were treated.According to its clinical pathology is divided into observation 1 group and observation 2 group.Serum samples were collected and serum CEA, CA19-9, CA125 and HE4 levels were analyzed statistically and the ROMA values were calculated according to menopausal status.Results Compared with the control group, the levels of CEA, CA19-9, CA125 and HE4 in the serum of observation group patients with endometrial carcinoma were significantly higher than those in the control group, the ROMA value of the menopausal state was significantly higher, the difference was statistically significant (P＜0.05).And with the progression of endometrial cancer staging, compared with the observation 1 group, the levels of CA19-9, CA125 and HE4 in the serum of the observation 2 group were significantly higher, the ROMA values of the menopausal states were significantly increased, the difference was statistically significant (P＜0.05).The combined detection rate of CEA, CA19-9, CA125, HE4 and ROMA in serum of patients with endometrial carcinoma was significantly higher than that of each index (P＜0.05).Conclusion The abnormally elevated levels of CEA, CA19-9, CA125, HE4, and ROMA in the serum of patients have important significance and role in the clinical diagnosis of endometrial cancer and its clinical staging.

The significance of serum HE4 ,CA125 and ROMA indexes in diagnosis of ovarian cancer to different menopausal status / 西安交通大学学报(医学版)

Objective To evaluate the significance of HE4 ,CA125 and ROMA indexes in the diagnosis of ovarian cancer in different menopausal status women .Methods After the gynecological mass was taken for pathological diagnosis ,a total of 73 cases of ovarian cancer (ovarian cancer group ,divided into early stage and late stage) and 66 cases of gynecological benign tumor (benign tumor group ) were selected .57 healthy women were selected as controls (control group ) . All groups were further divided into non-menopausal and postmenopausal groups .Serum levels of HE4 and CA125 were measured by chemiluminescence immunoassay and the ROMA index was calculated . Results ① The serum levels of HE4 , CA125 and ROMA in ovarian cancer group were significantly higher than those in benign tumor group and healthy control group (P<0 .01) .② When benign tumor group and control group were taken as a reference , the receiver operating characteristic (ROC ) curve analysis showed that the area under the curve (AUC) of HE4 ,CA125 and ROMA in the non-menopausal group and the postmenopausal group was (0 .944 ,0 .822 ,0 .941 vs .0 .994 ,1 .000 ,1 .000) ,respectively .③ In non-menopausal group ,HE4 has higher specificity and positive predictive value .The best cut off value was 75 .92 pmol/mL ,the diagnostic sensitivity and specificity were 73 .1% and 100% .In postmenopausal group ,CA125 has higher sensitivity , the optimum cut off value was 57 .65 U/mL ,the diagnostic sensitivity and specificity were 100% and 95 .4% .④ In the postmenopausal group ,there was no significant difference in serum CA 125 level between the early and late ovarian cancer patients (P> 0 .05) .Conclusion In the premenopausal group HE4 has a better differential diagnostic value .In postmenopausal group ,the ROMA index could give consideration to both sensitivity and specificity ,and had higher diagnostic efficacy .It plays roles in the diagnosis of ovarian cancer to establish the appropriate reference interval of HE4 ,CA125 and ROMA indexes according to the different menopausal status .

Clinical value of serum CA125 and HE4 combined with vaginal color Doppler in early screening of ovarian cancer among high-risk populations / 重庆医学

Objective To explore the clinical value of serum CA125 and HE4 combined with transvaginal color Doppler(TVCD)examination in early screening of ovarian cancer among high-risk populations.Methods The included research subjects were divided into 3 groups:100 cases in the healthy group,80 cases in the high-risk group and 32 cases in the ovarian cancer group.The serum CA125 and HE4 levels and ultrasonic scores were compared among 3 groups.Results The HE4 and CA125 levels and ultrasound scores in the ovarian cancer group were significantly increased compared with the other two groups,the difference was statistically significant(P＜0.01);the positive detection rate of CA125 plus HE4 levels combined with ultrasonic examination in the high-risk group was higher than that of other detection method(P＜0.05);the sensitivity and specificity of CA125+HE4 combined with vaginal ultrasound screening were obviously higher than those of other screening method,the difference was statistically significant(P＜0.05);the specificity of HE4 was significantly higher than that of CA125,but its sensitivity was lower than that of CA125(P＜0.05).Conclusion CA125 and HE4 combined with TVCD is helpful for early screening of ovarian cancer in high-risk populations,easy to save medical cost and improves its detection rate.

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78–0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.

Diagnosis of early ovarian cancer by combination use of tran svaginal color doppler sonography and HE4,CA125 detection / 上海预防医学

Objective To estimate the clinical value of diagnosing early ovarian cancer by using transvaginal color doppler sonography (TVCDS ) , combined with the levels of serum tumor markers HE 4 and CA125. Methods A total of 151 patients with adnexal masses admitted for elective surgery were selected .According to the postoperative pathologic results , they were divided into ovarian cancer group (group A, 48 cases) and ovarian benign lesions group (group B, 103 cases).All patients were examined by TVCDS and the determination of serum HE 4 and CA125 level before surgery . The results were compared with pathological diagnosis after surgery . Results Serum HE4 and CA125 levels of the patients in group A were higher than those in group B .TVCDS parameters S/D, PI and RI were significantly lower in group A than in group B .The accuracy , sensitivity , specificity , positive predictive value, negative predictive value of TVCDS and HE 4+CA125 in ovarian cancer diagnosis were 94 .70%, 93 .75%, 95 .15%, 90 .00%, 97 .03%, respectively .The values were higher than the value of the sepa -rate checks .Con clusion TVCDS combined determination of serum HE 4 and CA125 level is helpful to the improvement of clinical diagnosis in ovarian cancer .

Significance of serum human HE4 and CA 125 for diagnosis of epithelial ovarian cancer / 国际检验医学杂志

Objective To evaluate the value of HE4 ,CA125 in the diagnosis of epithelial ovarian cancer (EOC) .Methods A to‐tal of 54 samples with epithelial ovarian cancer ,64 suspicious benign pelvic mass ,and 60 health controls were consecutively enrolled in this study .Results Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125 and HE4 . Serum level of HE4 of the patients in the three group were 189 .94 pmol/L ,56 .74 pmol/L and 46 .36 pmol/L .Levels of CA125 were 89 .39 U/L ,45 .11 U/L and 34 .24 U/L .There were stastically significant differences between the groups(P<0 .05) .The ser‐um HE4 and CA125 levels of the patients with ovarian cancer at stage Ⅲ ,Ⅳ(HE4=236 .25 pmol/L ,CA125=206 .35 U/L) were significantly higher than the cases at stage Ⅰ ,Ⅱ(HE4=96 .36 pmol/L ,CA125=67 .8 U/L P<0 .05) .Benign pelvic mass as con‐trol ,the specificity (SP) was 86 .6% ,sensitivity (SN) was 82 .6% ,positive predictive value and negative predictive value of the ser‐um HE4 were 85 .71% ,71 .67% ,73 .84% ,and 84 .31% respectively .SN of CA125 was 86 .67% ,higher than that of HE4 (71 .67% ,P<0 .01) .The area under curves (AUC) of HE4 was 0 .87 higher than that of CA125 (0 .81) ,(P<0 .01) .Combing de‐tection of ovarian cancer was higher than that of HE4 and CA125 alone .SP was 95 .15% ,negative predictive value was 92 .13%(P<0 .01) .Conclusion Overall ,the level of serum CA125 and HE4 increase significantly ,which showes well diagnostic perform‐ance to EOC from benign diseases .The combined detection of CA125 and HE4 could improve the diagnostic power in cervical cancer prominently ,so it has great reference value in the diagnosis of epithelial ovarian cancer .

Biomarkers towards Ovarian Cancer Diagnostics: Present and Future Prospects

ABSTRACT Ovarian carcinoma accounts for highest mortality of all gynecologic malignancies as the disease is asymptomatic until late stages. Biomarkers such as CA-125 and HE4 are being currently used for diagnosis of ovarian cancer, but they show contradicting diagnostic accuracy. Therefore other biomarkers have been investigated for early detection of this disease, but no success has been obtained and no test has yet been recommended for screening a general population. In this instance, aptamers can be effectively used to identify tumor-specific antigens for early diagnosis and targeted therapy of ovarian cancer. This article provides an overview of the biomarkers/panels being explored as well as the potential of aptamers to improve current long-term survival rates of ovarian cancer.

Selecting the Best Cut-off Point of Serum HE-4 in Ovarian Cancer by ROC Curve / 现代检验医学杂志

Objective Using ROC curve to determine the best cut-off point of serum HE-4 in the diagnosis of ovarian cancer and provide important value to diagnosis early ovarian cancer.Methods The levels of serum HE-4 in 68 ovarian cancer pa-tients,42 ovarian benign tumor patients and 30 healthy female were detected by electrochemistry irradiance method.The ROC curve was drawn and the cut-off point of HE-4 was determined by statistical software.Results The levels of serum HE-4 were all non-normal distribution in the groups of ovarian cancer,ovarian benign tumor and healthy controls.Whats more,there was no significant difference between ovarian benign tumor group and normal control group.And compared with benign ovarian tumors and normal control group,the level of HE-4 in ovarian cancers was significantly increased (P <0.01).It would be best for diagnosis when the level of serum HE-4 was 108pmol/L in ovarian cancer.Youden’s index showed the maximum (0.713)and the sensitivity and specificity of diagnosing were 77.9% and 93.1% respectively.The positive predictive value was 91.4% and negative predictive value was 91.4%.At the same time,the positive likelihood ratio was 11.6 and the negative likelihood ratio was 0.2,odds ratio reached to 47.3.Conclusion The detection of HE-4 is an ideal mark for diagnosing and excluding ovarian cancer.Selecting 108 pmol/L as ovarian cancer diagnosis point is relative appro-priate.

CLINICAL VALUE OF CA125, CA153, HE4 JOINT DETECTION IN DIAGNOSIS OF GYNE-COLOGICAL MALIGNANCIES / 现代医院

Objective To investigate the clinical value of CA125, CA153, HE4 joint detection in diagnosis of gynecological malignancies.Methods 70 cases of gynecological malignancies were selected from our hospital in 2013, 72 cases of benign gynecological diseases selected in the same period, and 70 healthy controls were selected. The expression levels of CA125, CA153 and HE4 were detected and statistically analyzed.Results The positive rate of serum CA125 in the gynecological malignancies group was higher than that in the benign gynecological disease group (p <0.05).The positive rate of serum HE4 in the gynecological malignancies group was higher than that in the benign gynecological disease group (p <0.01).The positive rate of CA125, CA153, HE4 joint detection in the gy-necological malignancies group (up to 72.9%) was also significantly higher than that in the benign gynecological dis-ease group (p <0.01).Conclusion is a single tumor marker with the highest sensitivity and specificity for diagno-sis of gynecological malignancies.CA125, CA153, HE4 joint detection can improve the positive rate of diagnosis of gynecological malignancies.

Comparison of HE4, CA125, and Risk of Ovarian Malignancy Algorithm in the Prediction of Ovarian Cancer in Korean Women

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.

Effect of high dose metformin on serum HE4, LPA and regulatory T cells in patients with ovarian cancer / 中国生化药物杂志

Objective To analysis the effect of high dose metformin on serum HE4, LPA and regulatory T cells in patients with ovarian cancer.Methods 80 cases of unilateral ovarian cancer patients were given surgery and conventional chemotherapy ,were divided into four groups according to single metformin dose: (group A:0.25g each time, B group:0.25g each time, group C:0.25g each time; group D: conventional treatment only) and three times a day oral administration of metformin and two weeks in a row , before and after the treatment of detection each serum HE4, LPA, transformation growth factor beta 1 (TGF -beta 1), interleukin -10 (IL-10) content, and CD4 +CD25 +CD127 regulating T cell percentage.ResuIts Compared with B, C, and D group, the efficacy of patients in group A was better, as follows: Serum HE4 content decreased significantly ( P<0.05 ); serum LPA content decreased significantly ( P<0.05 ); blood CD4 +CD25 +CD127 regulatory T cell percentage decreased significantly ( P<0.05 ); serum TGF beta 1, IL-10 content decreased significantly ( P<0.05 ) .The results were statistically significant .ConcIusion High dose of metformin can reduce serum HE4 , LPA content, reduce the adjusting the percentage of T cells and related cytokines in patients with ovarian cancer , and play a positive role in inhibit cancer cell proliferation and invasion .

Correlation between eIF3a and HE4 expression and ovarian cancer / 中南大学学报(医学版)

Objective: To investigate the correlation between eukaryotic translation initiation factor 3, subunit A (eIF3a) and human epididymis protein 4 (HE4) expression and ovarian cancer. Methods: RT-PCR or immunohistochemistry was used to examine eIF3a and HE4 mRNA or protein expression in ovarian tissues from patients with ovarian cancer (n=181) or benign ovariantumors, or from the healthy women. Results: hTere were signiifcant differences in mRNA and protein expression of eIF3a and HE4 among normal ovarian tissues, benign ovarian tumor tissues, and ovarian cancer tissues (P<0.05). hTere were signiifcant differences in mRNA expression of eIF3a and HE4 between the normal tissues and the ovarian cancer tissues, or between the benign ovarian tumor tissues and the normal tissues (P<0.001). hTe mRNA expression of eIF3a in the normal ovarian tissues was signiifcantly higher than that in the benign ovarian tumor tissues or that in the ovarian cancer tissues. hTe mRNA expression of HE4 was gradually increased from the normal ovarian tissues, the benign ovarian tumor tissues to the ovarian cancer tissues. hTe mRNA expression of HE4 in the ovarian cancer tissues was signiifcantly higher than that in the benign ovarian tumor tissues (P<0.001). Positive expression rates for eIF3a or HE4 protein in normal, benign tumor, and cancer tissues were 0, 66.7%, and 81.0% or 0, 27.8%, and 56.2%, respectively. hTere were signiifcant differences in positive expression rates of eIF3a protein and HE4 protein between the ovarian tumor tissues and benign ovarian tumor tissues, between the ovarian cancer tissues and the normal ovarian tissues, or between the benign ovarian tumor tissues and the normal ovarian tissues (P<0.001). hTe eIF3a protein expression was positively correlated with HE4 protein expression (r=0.575,P<0.05). Conclusion: The expressions of eIF3a and HE4 are associated with ovarian cancer, and extracellular regulated protein kinases may play a role in the interaction between eIF3a and HE4.

HE4 expression in serous ovarian cancer tissues and its relationship with clinicopathological features / 实用肿瘤学杂志

Objective To investigate the expression level of human epididymis protein 4 ( HE4 ) in se-rous ovarian cancer tissues and its relationship with clinicopathological features .Methods The expression level of HE4 in 140 serous ovarian cancer patients and its relationship with clinicopathological features were detected by immunohistochemistry.To compare the correlation between HE4 and CA125, the histological expressionOf CA125 was also detected by IHC .Results the positive expression rate of HE 4 and CA125 in moderately and poorly differentiated serous ovarian cancer tissues were respectively 89.76%and 81.89%;the positive expression rate in well differentiated group were respectively 46.61% and 15.38%,in the advanced stages were 92.44%and 83.19%,in the early stages were 47.62%and 33.33%.the positive expression rate of lymphatic metastasis were 95.65%and 84.35%,without lymphatic metastasis were 40.00%and 36.00%,the positive expression rate of peritoneal implantation were 90.00% and 87.27%, without peritoneal implantation were 70.00% and 33.33%;the positive expression rate of ascites were 89.76% and 79.53%,without ascites were 46.15% and 38.46%.Besides,the positive expression rates of HE4 and CA125 were 86%and 76%,the differences were sta-tistically significant.Both the positive expression in ovarian cancer are correlated positively (P0.05).Conclusion The expression of HE4 in serous ovarian cancer is related with FI-GO stages,the degree of tumor differentiation ,lymph node metastasis and ascites .

Construction and expression of two kinds of HE4 fusion protein / 中国免疫学杂志

Objective:To express human epididymis protein 4 (HE4) in prokaryotic cells,purify the expressed product and de-termine its activity by immunoassay kit.Methods: The gene encoding HE 4 was cloned using RT-PCR technique from total RNA of ovarian carcinoma cells ES-2,the amplified HE4 gene was cloned into prokaryotic expression vector pGEX-4T-1 and PET26b respective-ly.The recombinant plasmid pGEX-4T-1-HE4 and PET26b-HE4 were constructed and transformed into E.coli BL21 cells respectively, and protein ( GST-HE4 and His-HE4 ) expressions were induced by IPTG and identified by SDS-PAGE and commercial ELISA kit.Results:Restriction analysis and sequencing proved that recombinant plasmid pGEX -4T-1-HE4 and PET26b-HE4 were constructed correctly.The expressed recombinant proteins ,with the relative molecular mass of about 38 000 and 12 000 ,showed specific binding to monoclonal antibody against HE 4.Conclusion:Two kinds of recombinant HE 4 protein are successfully expressed in prokaryotic cells , which laid a foundation of preparation of immunoassay reagents.

The prognostic value of serum HE4 in lung cancer / 中华放射医学与防护杂志

Objective The study was designed to investigate the serum levels of HE4 in patients with lung cancer,and explore its prognostic value.Methods Blood samples of 106 healthy adults and 191 patients with lung cancer before treatment were measured by means of ELISA for HE4 levels in different stages and pathological types,for analyzing prognostic effect of HE4.Results The serum levels of HE4 in patients with lung cancer (median level 91.63 pmol/L) were significantly higher than control group (median level 56.42 pmol/L) (U =3 081.00,P ＜ 0.05).AUC of serum HE4 was 0.85,with a cut-off value of 82.70 pmol/L (specificity =95.31％,sensitivity =62.32％).HE4 expression was not statistically related to clinical stage and pathological types of lung cancer.The median overall survival (mOS) was 36.87 months in the HE4-low group and 30.43 months in the HE4-high group (P ＜0.05),respectively.HE4 level was an independent prognostic factor for overall survival (HR =2.15,95％ CI 1.49-3.12,P ＜ 0.05).Conclusions The prognosis of patients with high HE4 expression is poor.Therefore,it might be necessary for patients with high level of HE4 to receive more aggressive adjuvant therapy.