血清HE4和CA125联合检测预测盆腔包块患者卵巢癌的风险

目的:探讨新型肿瘤标记物人附睾分泌蛋白4(HE4)和CA125联合检测预测盆腔包块患者上皮性卵巢癌(EOC)风险的价值。方法:将诊断为盆腔包块拟行手术的患者纳入本研究。测定患者术前血清HE4和CA125水平,分别用绝经后和绝经前预测模型(ROMA)将患者划分至高危组和低危组,评估预测模型的应用价值。结果:评估了191例患者,其中138例盆腔良性疾病,53例盆腔恶性肿瘤,包括36例EOC。绝经后组盆腔良性疾病12例,8例划分至低危组,特异性66.7%(95%CI=40.0～93.3),恶性肿瘤37例,35例划分至高危组,敏感性94.6%(95%CI=87.0～101.9),EOC28例(含9例早期),全划分至高危组,敏感性100.0%。绝经前组良性疾病126例,103例划分至低危组,特异性81.7%(95%CI=75.0～88.5),16例恶性肿瘤,12例划分至高危组,敏感性75.0%(95%CI=54.0～96.2),EOC8例(含2例早期),全划分至高危组,敏感性100.0%。结论:ROMA成功地将盆腔恶性肿瘤患者划分至高危组,其中EOC患者全被正确地划分至高危组,可用于将恶性肿瘤患者尤其是EOC患者分流至有治疗经验的肿瘤医师及治疗中心。     

血清CA125及HE4诊断卵巢癌的研究进展

目前临床用于卵巢癌早期诊断的主要肿瘤标记物是血清糖链抗原125(CA125),CA125诊断卵巢癌的敏感性及特异性低。血清人附睾蛋白4(HE4)在卵巢癌中呈高表达,尤其是浆液性卵巢癌,其与CA125联合检测可有效提高卵巢癌的早期诊断率。本文就血清CA125和HE4单独及联合检测诊断卵巢癌的研究进展做一综述。     

血清HE4及CA125对子宫内膜癌宫外转移的预测价值

目的:评估术前血清HE4和CA125联合检测在子宫内膜癌(EC)的子宫外转移的诊断价值。方法:回顾分析327例EC患者的临床病理资料,检测血清HE4和CA125水平,分析HE4及CA125与临床病理参数的关系,计算诊断评价指标,绘制受试者工作特征(ROC)曲线,计算AUC值。结果:患者血清HE4和CA125水平与病灶范围大小、肌层浸润深度、肿瘤分化程度、临床分期、有无子宫外转移等有关,差异有统计学意义(P0.01)。血清HE4、CA125单项检测子宫外转移时,HE4敏感度最高,为57.81%,联合诊断能显著提高敏感度达79.68%。两项单独检测的ROC-AUC值分别为0.740、0.714,而联合诊断的ROC-AUC值为0.810,差异有统计学意义(P0.001)。结论:血清HE4和CA125联合预测EC患者的子宫外转移比单项检测更具优势。     

联合检测人附睾蛋白4与血清CA125用于诊断卵巢上皮性癌的诊断价值

目的:研究人附睾蛋白4(HE4)在卵巢上皮性癌患者血清及尿液中的表达水平,探讨其联合血清CA125用于卵巢上皮性癌诊断的临床应用价值。方法:采用酶联免疫吸附法(ELISA法)检测50例卵巢上皮性癌患者、38例卵巢良性肿瘤患者和40例正常人血清及尿液中的HE4水平和血清CA125水平。结果:卵巢癌患者组血清及尿液中的HE4水平明显高于卵巢良性肿瘤组及正常对照组,差异均有统计学意义(P<0.05),血清及尿液HE4水平在卵巢良性肿瘤组及正常对照组之间差异无统计学意义(P>0.05)。血清HE4检测卵巢上皮性癌的灵敏度、特异度分别为58.0%、87.2%,与血清CA125联合检测其灵敏度、特异度提高至86.0%、89.7%;尿液HE4检测卵巢上皮性癌的灵敏度、特异度分别80.0%、91.0%,与血清CA125联合检测其灵敏度、特异度可达90.0%、94.9%;联合检测血清HE4、尿液HE4和血清CA125的灵敏度和特异度高达94.0%、94.9%。结论:联合检测血清及尿液HE4与血清CA125可显著提高卵巢上皮性癌的诊断率。     

血清人附睾分泌蛋白4（HE_4）和CA_（125）在卵巢癌患者手术及化疗前后的变化

目的检测卵巢癌患者手术及化疗前后HE4和CA125的血清值,探讨卵巢癌患者治疗前后HE4、CA125的变化情况。方法采用酶联免疫吸附试验（ELISA法）检测21例卵巢癌患者治疗过程中血清HE4和CA125水平。数据使用SPSS13.0进行统计学分析。结果卵巢癌患者术后行常规化疗,血清HE4及CA125的水平基本下降到正常。术前HE4中位数水平为796.32pmol/L,第2次后基本恢复正常,为135.61pmol/L;患者术前CA125中位数水平为1280kU/L,第3次化疗后为30.4kU/L,恢复正常。卵巢癌患者治疗过程中HE4与CA125具有较强的相关性,相关系数为0.811。结论 HE4可能作为有助于评判疗效的另一种血清学标志物。     

血清CA125、HE4以及ROMA指数在卵巢癌早期诊断中的应用价值

目的:探讨人附睾蛋白4(HE4)、糖类抗原125(CA_(125))及卵巢癌风险预测模型(ROMA)在卵巢癌早期诊断中的应用价值。方法:采用酶联免疫吸附试验及化学发光法检测53例国际妇产科联合会(FIGO)2014年卵巢癌分期Ⅰ、Ⅱ期卵巢癌患者及54例卵巢良性肿瘤患者血清HE4及CA_(125)水平,根据受试者绝经情况,通过计算ROMA指数,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC)。结果:卵巢癌检测HE4、CA_(125)水平及ROMA指数分别为416.19±134.04 pmol/L、895.97±252.16 U/ml及(59.10±4.49)%;卵巢良性肿瘤组分别为33.61±3.07 pmol/L、33.98±4.99 U/ml及(20.08±5.07)%,卵巢癌组血清HE4、CA_(125)水平及ROMA指数高于卵巢良性肿瘤组,差异有统计学意义(P0.05)。血清HE4、CA_(125)水平和ROMA指数对卵巢癌诊断的敏感度分别为92.45%、69.81%、96.23%,特异度分别为79.63%、70.37%、81.48%,ROC-AUC分别为0.943、0.803、0.975。结论:联合检测HE4和CA_(125)计算ROMA指数对卵巢癌早期诊断敏感度和特异度较高。     

CA125、HE4、ROMA及RMI在附件包块诊断中的应用价值

附件包块病因复杂多样,相应的临床决策千差万别。因此,对附件包块性质的预判是临床诊断的首要任务,也是临床工作的难点和要点。CA125是鉴别附件包块良恶性的最常见指标,但影响因素多,不建议单独用于绝经前女性。人附睾蛋白4（HE4）特异度高,联合CA125可显著提高附件包块良恶性鉴别诊断的准确率。针对附件包块拟行手术的患者,推荐应用卵巢恶性肿瘤风险模型（ROMA）和恶性肿瘤风险指数（RMI）进行评估,高危者应转诊到妇科肿瘤专科。     

CA125、HE4、ROMA及RMI在附件包块诊断中的应用价值

附件包块病因复杂多样,相应的临床决策千差万别。因此,对附件包块性质的预判是临床诊断的首要任务,也是临床工作的难点和要点。CA125是鉴别附件包块良恶性的最常见指标,但影响因素多,不建议单独用于绝经前女性。人附睾蛋白4（HE4）特异度高,联合CA125可显著提高附件包块良恶性鉴别诊断的准确率。针对附件包块拟行手术的患者,推荐应用卵巢恶性肿瘤风险模型（ROMA）和恶性肿瘤风险指数（RMI）进行评估,高危者应转诊到妇科肿瘤专科。     

人附睾分泌蛋白4(HE4)对卵巢上皮性癌的预测价值

卵巢癌是妇女生殖系统中常见的恶性肿瘤,早期诊断卵巢癌可明显改善患者预后。人附睾分泌蛋白4(human sapiens epididymis specific protein4,HE4)作为一种新型的肿瘤标记物,其在卵巢癌的早期诊断及疾病监测方面均具有很好的临床价值。     

联合检测HE4、CA125和CEA在卵巢上皮癌中的诊断意义

目的:探讨单独及联合检测HE4、CA125及CEA对卵巢上皮癌的诊断意义。方法:电化学发光法检测79例卵巢上皮癌、83例卵巢良性肿瘤患者及82例健康查体女性血清中HE4、CA125及CEA水平。分析HE4、CA125及CEA水平与卵巢上皮癌临床病理特征的关系。受试者工作曲线(ROC曲线)分析单独与联合检测卵巢上皮癌的灵敏度和特异度。结果:卵巢上皮癌组的血清HE4、CA125、CEA水平明显高于卵巢良性肿瘤组及健康查体组,差异均有统计学意义(P均0.05),后两组比较则无明显差异(P0.05)。卵巢上皮癌组患者中,临床病理期别越晚,血清HE4水平越高(P0.05),肿瘤分化程度越低,CA125水平越高(P0.05)。联合检测HEA、CA125和CEA ROC曲线下面积大于单独检测(P0.05)。结论:联合检测HE4、CA125、CEA比单独检测对卵巢上皮癌有更好的诊断价值。     

Evaluation of HE4, CA125, risk of ovarian malignancy algorithm (ROMA) and risk of malignancy index (RMI) as diagnostic tools of epithelial ovarian cancer in patients with a pelvic mass

Objective

Diagnostic factors are needed to improve the currently used serum CA125 and risk of malignancy index (RMI) in differentiating ovarian cancer (OC) from other pelvic masses, thereby achieving precise and fast referral to a tertiary center and correct selection for further diagnostics. The aim was to evaluate serum Human Epididymis protein 4 (HE4) and the risk of ovarian malignancy algorithm (ROMA) for these purposes.

Methods

Serum from 1218 patients in the prospective ongoing pelvic mass study was collected prior to diagnosis. The HE4 and CA125 data were registered and evaluated separately and combined in ROMA and compared to RMI.

Results

809 benign tumors, 79 borderline ovarian tumors, 252 OC (64 early and 188 late stage), 9 non-epithelial ovarian tumors and 69 non-ovarian cancers were evaluated. Differentiating between OC and benign disease the specificity was 62.2 (CA125), 63.2 (HE4), 76.5 (ROMA) and 81.5 (RMI) at a set sensitivity of 94.4 which corresponds to RMI = 200. The areas under the curve (AUC) were 0.854 (CA125), 0.864 (HE4), 0,897 (ROMA) and 0.905 (RMI) for benign vs. early stage OC. For premenopausal benign vs. OC AUC were 0.925 (CA125), 0.905 (HE4), 0.909 (ROMA) and 0.945 (RMI).

Conclusion

HE4 and ROMA helps differentiating OC from other pelvic masses, even in early stage OC. ROMA performs equally well as the ultrasound depending RMI and might be valuable as a first line biomarker for selecting high risk patients for referral to a tertiary center and further diagnostics. Further improvements of HE4 and ROMA in differentiating pelvic masses are still needed, especially regarding premenopausal women.     

The use of HE4 in the prediction of ovarian cancer in Asian women with a pelvic mass

ObjectiveThe purpose of this study was to evaluate the performance of human epididymis protein 4 (HE4) and the Risk of Ovarian Malignancy Algorithm (ROMA) for distinguishing between benign and malignant pelvis masses in Asian women.MethodsThis was a prospective, multicenter (n = 6) study with patients from six Asian countries. Patients had a pelvic mass on imaging and were scheduled to undergo surgery. Serum CA125 and HE4 were measured on preoperative samples. CA125, HE4, and ROMA were evaluated for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).ResultsA total of 414 women with an adnexal mass were evaluated, of which 65 had epithelial ovarian (EOC) cancer, 16 had borderline tumors and 11 had other malignant diseases. Compared to CA125, HE4 had lower sensitivity (56.9% vs 90.8%) and NPV (91.8% vs 97.3%), but improved specificity (96.9% vs 67.1%) and PPV (78.7% vs 35.8%) for differentiating between benign pelvic mass and EOC. ROMA had similar sensitivity (89.2% vs 90.8%) and NPV (97.6% vs 97.3%) as CA125, but showed improved specificity (87.3% vs 67.1%) and PPV (58.6% vs 35.8%). ROMA accurately predicted 87.3% of benign cases as low risk, and 82.6% of stage I/II EOC and 89.2% of all EOC as high risk.ConclusionROMA showed similar sensitivity as CA125 but improved specificity and PPV, especially in premenopausal women. Using ROMA may help predict if a pelvic mass is benign or malignant and facilitate subsequent management planning.     

Comparison of HE4, CA125 and ROMA algorithm in women with a pelvic mass: Correlation with pathological outcome

ObjectiveThe quality of first surgery is one of the most important prognostic factors in ovarian cancer patients. Pre-surgical distinction of benign and malignant pelvic mass plays a critical role in ovarian cancer management and survival. The aim of this study was to evaluate the clinical performance of ROMA algorithm and of CA125 and HE4 in the triage of patients with a pelvic mass undergoing surgery, in order to discriminate benign from malignant disease.MethodsThree hundred and forty-nine pre- and post-menopausal women, aged 18 years or older undergoing surgery because of a pelvic mass were enrolled: serum concentrations of CA125 and HE4 were determined and ROMA was calculated for each sample.ResultsMedian serum CA125 and HE4 levels were higher in patients with EOC compared to subjects with benign disease (p < 0.0001). The resultant accuracy (using Receiver Operating Characteristics, ROC Area) values for HE4, CA125 and ROMA showed a good performance ranging from 89.8% for CA125 in pre-menopausal patients to 93.3% for ROMA in post-menopausal patients: AUC for ROMA resulted significantly higher in comparison to CA125 alone (93.3% vs 90.3%, p = 0.0018) in post menopausal patients. A sub-analysis considering the 40 patients with endometrioid disease showed the highest accuracy of HE4 in these patients.ConclusionsData presented confirm the accuracy of HE4 and of the ROMA algorithm in the distinction of ovarian carcinoma from benign disease, with a trend towards better performance for ROMA than for CA125 alone, statistically significant in postmenopausal patients.     

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

Archives of Gynecology and Obstetrics - To determine the diagnostic value and clinical significance of serum HE4 levels in differentiating between benign and malignant ovarian disease in patients...     

血清miR-222、HE4及CA125水平联合ROMA指数对上皮性卵巢癌的诊断价值

目的:探讨血清miR-222、血清人附睾蛋白4(HE4)及糖类抗原125(CA125)水平联合ROMA指数对上皮性卵巢癌(EOC)的诊断价值.方法:选取2016年1月至2019年12月海南西部中心医院收治的120例EOC患者、100例上皮性卵巢良性肿瘤患者和50例正常健康女性作为研究对象.实时定量PCR法检测miR-2...     

Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer

Objective

To evaluate the diagnostic performance of HE4 and CA125 in patients presenting with suspicious malignant ovarian cysts. We especially wanted to investigate the levels of HE4 and CA125 with regard to the gene and histology-unifying model of type I and type II epithelial ovarian cancer (EOC).

Methods

Plasma from 373 women presenting with a suspicious malignant ovarian cyst was collected prior to surgery. Histology, grade, and stage were determined according to FIGO-classification. HE4 and CA125 were analyzed using ELISA, and the markers were evaluated for significance separately and in combination. Receiver operating curves, the area under the curve, sensitivity and specificity were estimated.

Results

The combination of HE4 and CA125 resulted in the best diagnostic power in comparing benign tumors to EOC (ROC AUC 0.93, sensitivity 94.4% at 75% specificity) for type II. Diagnostic power in type I (ROC AUC 0.79, sensitivity 61.9% at 75% specificity) was less impressive. In particular, mucinous benign vs. malignant tumors could not significantly be separated by the dual marker combination. Impressively high ROC AUC 0.99 was found for the late stage type II EOC with 100% sensitivity at 75% specificity.

Conclusions

HE4 and CA125 have a good ability to diagnose the more aggressive type II tumors but a poor diagnostic ability when patients are presenting with slow-growing type I in the early stage. Our results support the hypothesis that EOC should be looked upon as several different diseases, and that we lack biomarkers for sub-groups of EOC.     

Tumour-associated antigen CA 125 in patients with ovarian cancer

The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6-30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.     

Preoperative evaluation of serum CA 125 levels in patients with primary epithelial ovarian cancer

Serum CA 125 levels were measured preoperatively in 100 women undergoing diagnostic laparotomy for palpable adnexal masses. All 11 patients with frankly malignant nonmucinous ovarian carcinoma had serum CA 125 levels greater than 35 U/mL and nine of the 11 had serum CA 125 levels greater than 65 U/mL. If patients with mucinous and borderline lesions were included, serum CA 125 was greater than 35 U/mL in 11 of 18 and greater than 65 U/mL in nine of 18 patients. Among 14 individuals with pelvic masses and CA 125 greater than 65 U/mL, 13 had some form of gynecologic malignancy. These results suggest that CA 125 assay can be used as a diagnostic adjunct for discriminating benign from malignant pelvic masses.