血清MIC-1和CA125在卵巢上皮癌诊断及预后中的应用研究

目的：探讨巨噬细胞抑制因子-1（MIC-1）和CA125的卵巢癌诊断和预后判断价值。方法通过检测92例未经治疗的卵巢上皮癌患者（观察组）和96例健康女性（对照组）血清样本中的MIC-1和CA125水平,分析血清MIC-1和CA125水平与卵巢癌的关系;通过ROC曲线评价MIC-1和CA125单项及联合应用的卵巢癌诊断效能;通过对其中74例卵巢癌患者按术后残瘤大小和首次化疗敏感性结果分组,比较两组治疗前MIC-1和CA125水平,评价MIC-1和CA125的疗效评价价值;并通过分析68例患者的MIC-1和CA125水平与无瘤生存时间（relapse free survival,RFS）的关系评价其预后判断价值。结果观察组血清MIC-1水平显著高于对照组（P＜0.001）;MIC-1诊断卵巢癌的ROC（AUC=0.945）与CA125的ROC（AUC=0.966）比较差异无统计学意义,MIC-1和CA125联合应用的卵巢癌诊断效能显著提高（AUC=0.966）。术前CA125水平与术后残瘤大小显著相关（P=0.07）;术前血清MIC-1水平与化疗敏感性显著相关（P=0.001）,并且血清MIC-1水平与患者RFS呈负相关。结论 MIC-1和CA125联合检测可提高卵巢癌的诊断率,MIC-1高水平预示卵巢上皮癌患者存在较大的耐药风险,且MIC-1可作为预测卵巢癌患者生存期的独立指标。     

A multiparametric panel for ovarian cancer diagnosis, prognosis, and response to chemotherapy.

PURPOSE: Our goal was to examine a panel of 11 biochemical variables, measured in cytosolic extracts of ovarian tissues (normal, benign, and malignant) by quantitative ELISAs for their ability to diagnose, prognose, and predict response to chemotherapy of ovarian cancer patients. EXPERIMENTAL DESIGN: Eleven proteins were measured (9 kallikreins, B7-H4, and CA125) in cytosolic extracts of 259 ovarian tumor tissues, 50 tissues from benign conditions, 35 normal tissues, and 44 tissues from nonovarian tumors that metastasized to the ovary. Odds ratios and hazard ratios and their 95% confidence interval were calculated. Time-dependent receiver operating characteristic curves for censored survival data were used to evaluate the performance of the biomarkers. Resampling was used to validate the performance. RESULTS: Most biomarkers effectively separated cancer from noncancer groups. A composite marker provided an area under the curve of 0.97 (95% confidence interval, 0.95-0.99) for discriminating normal and cancer groups. Univariately, hK5 and hK6 were positively associated with progression. After adjusting for clinical variables in multivariate analysis, both hK10 and hK11 significantly predicted time to progression. Increasing levels of hK13 were associated with chemotherapy response, and the predictive power of hK13 to chemotherapy response was improved by a panel of five biomarkers. CONCLUSIONS: The evidence shows that a group of kallikreins and multiparametric combinations with other biomarkers and clinical variables can significantly assist with ovarian cancer classification, prognosis, and response to platinum-based chemotherapy. In particular, we developed a multiparametric strategy for predicting ovarian cancer response to chemotherapy, comprising several biomarkers and clinical features.     

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

Background CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer.Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer.Results Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone.Conclusion Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.Subject terms: Diagnostic markers, Ovarian cancer     

Prognostic value of kallikrein-related peptidase 6 protein expression levels in advanced ovarian cancer evaluated by automated quantitative analysis (AQUA)

Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered important prognostic biomarkers in cancer. In the present study, we sought to determine the prognostic value of kallikrein-related peptidase 6 (KLK6) in ovarian cancer using a novel method of compartmentalized in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For evaluation of KLK6 protein expression, we used an immunofluorescence-based method of automated in situ quantitative measurement of protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred and thirty-five of 150 cases had sufficient tissue for AQUA analysis. In univariate survival analysis, low tumor KLK6 expression was associated with better outcome for overall survival over 3 years (P = 0.019). There was no association between tumor KLK6 expression and progression-free survival (P = 0.128). In multivariate survival analysis, adjusting for well-characterized prognostic variables, low tumor KLK6 expression level was one of the most significant predictor variable for overall survival (95% confidence interval, 1.19-3.50; P = 0.009). High tumor KLK6 protein expression is associated with inferior patient outcome in ovarian cancer. KLK6 may represent a promising disease biomarker and therapeutic target in ovarian cancer.     

可溶性E-钙粘蛋白、糖类抗原125、人附睾蛋白4联合检测在卵巢癌早期诊断中的临床价值

目的:探讨联合检测sE-CAD、CA125和HE4在卵巢癌早期诊断中的临床应用价值,以改善传统CA125和HE4检测在早期卵巢癌诊断中的不足。方法:检测40例健康体检者、64例卵巢良性肿瘤患者、112例卵巢癌患者（I期:14例,II期:23例,Ⅲ期:41例,IV期:34例）血清中sE-CAD、CA125和HE4的表达水平,结合临床资料,进行相关统计学分析。结果:不同临床分期卵巢癌组、卵巢良性疾病组和健康对照组sE-CAD、CA125和HE4的表达水平比较,差异均有统计学意义（P＜0.05）,卵巢良性疾病组与健康对照组比较,CA125表达水平明显升高,差异具有统计学意义（P＜0.05）,sE-CAD、HE4水平则无显著变化（P＞0.05）。sE-CAD、CA125和HE4联合检测用于早期卵巢癌（I-II期）的诊断时,其灵敏度、特异度、阳性预测值和阴性预测值分别达到90.8%、91.1%、83.4%、93.6%,ROC曲线下面积也升高至0.956 5,95%CI为0.916 9~0.996 1,比各指标单独检测均有所提升。结论:sE-CAD、CA125和HE4联合检测具有较高的灵敏度、特异度和ROC曲线下面积,是诊断早期卵巢癌（I-II期）较为理想的生物标志物组合。     

B7-H1在卵巢癌组织中表达的临床意义

目的 探讨B7-H1在卵巢癌组织中表达的临床意义.方法 将收治的112例上皮性卵巢癌及10例良性卵巢囊肿的组织蜡块制作成组织芯片,免疫组化检测芯片协同刺激分子B7-H1的表达情况,χ2检验B7-H1表达水平与患者临床病理参数的关系.生存分析采用Kaplan-Meier法和Log-rank检验及多因素COX回归.结果 B7-H1在良性卵巢囊肿中均为低表达,在卵巢癌组织中高表达率为55.4%(62/112);其表达水平与患者年龄、组织类型、细胞分化、肿瘤大小及是否合并CA125升高无关(P>0.05),而与患者FIGO分期及是否转移密切相关(P<0.05);B7-H1高表达组与低表达组患者无进展生存期(progression-free survival,PFS)和总生存期(overall survival,OS)比较差异均有统计学意义(χ2值分别为24.9和17.51,P值均<0.001).COX回归分析表明,B7-H1表达水平和FIGO分期是影响患者生存的独立预后因素.结论 卵巢癌组织中B7-H1的表达水平与预后差和生存期短相关,可为卵巢癌的免疫靶向治疗提供思路.     

Circulating biomarker tissue kallikrein-related peptidase KLK5 impacts ovarian cancer patients’ survival

BackgroundEffective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently needed in ovarian cancer. Kallikrein-related peptidases, including KLK5, have been reported to play an important role in the course of the disease.Patients and methodsKLK5 antigen content was determined by enzyme-linked immunosorbent assay in ovarian cancer patients’ [FIGO (International Federation of Gynecology and Obstetrics) stages I–IV, n = 52] serum as well as ascitic fluid and compared with KLK5 content in serum of patients with benign ovarian tumors (n = 45).ResultsKLK5 antigen content was significantly elevated in the serum of ovarian cancer patients compared with the serum of patients with benign ovarian tumors. Forty-two of 52 ovarian cancer serum samples, 42 of 43 benign ovarian tumor serum samples, and all 41 ascitic fluid samples were KLK5 positive. Elevated KLK5 antigen in serum and ascitic fluid of ovarian cancer patients was a prognostic factor for progression-free survival.ConclusionsOur data support the finding that ovarian cancer patients release significant amounts of KLK5 into serum and ascitic fluid but KLK5 antigen is low in serum of patients with benign ovarian tumors. Increased serum and ascitic fluid KLK5 levels are associated with poor patient outcome, thus underlining the importance of KLK5 as a biomarker for early detection as well as for disease management in ovarian cancer.     

Multiplexed bead-based immunoassay of four serum biomarkers for diagnosis of ovarian cancer

The purpose of the present study was to evaluate multiplex liquid assay-based measurement of multiple ovarian cancer-associated biomarkers such as hemoglobin, haptoglobin and apolipoprotein E, together with CA125, which has been widely used in the diagnosis of ovarian cancer, in order to provide a higher diagnostic power. We measured the serum levels of CA125, hemoglobin, haptoglobin and apolipoprotein E from the serum of 76 healthy individuals and 69 ovarian cancer patients using a multiplex liquid assay system, Luminex 100. The results were analyzed according to normal versus ovarian cancer, tumor stages and tumor histology. In addition, to validate the use of these biomarkers for the diagnosis of ovarian cancer, the sensitivity and specificity of each biomarker was analyzed by its receiver operating characteristics (ROC) curve. The serum levels of all four biomarkers in ovarian cancer patients were significantly higher than those of healthy individuals. When CA125 was combined with the biomarkers, the overall sensitivity and specificity were significantly improved in the ROC curve, which showed 95 and 75% sensitivity and specificity, respectively. At 95% specificity for all stages the sensitivity increased to 75% compared to 41% for CA125 alone. For stage I+II increased the sensitivity to 68% from 36% for CA125 alone. For stage III+IV the corresponding values were 100 and 95%, respectively. Taken together, the new combination of hemoglobin, haptoglobin and apolipoprotein E with CA125 significantly improved both the sensitivity and the specificity of ovarian cancer diagnosis compared with those of individual biomarkers. These findings suggest the benefit of the combination of these markers for the diagnosis of ovarian cancer.     

卵巢癌脂质组学诊断标志物的筛选及其效果研究

目的 卵巢癌是女性生殖器官常见的恶性肿瘤之一,90％的卵巢癌患者诊断时已进展到晚期(Ⅲ/Ⅳ期).尽管治疗方式的不断改进,但晚期卵巢癌患者5年总生存率为20％,而早期卵巢癌患者5年总生存率＞90％.本研究旨在识别卵巢癌脂质组学诊断生物标志物,提高卵巢癌早期诊断的准确性.方法 采用稀疏组lasso变量筛选方法和单因素分析相结合的方法,对2011-03-01-2013-07-31哈尔滨医科大学附属肿瘤医院的139例卵巢癌患者和76例对照患者的血浆脂质组学数据进行分析,筛选可用于诊断卵巢癌脂质组学的生物标志物,在差异代谢物中选择与CA125相关性小的物质作为最终诊断标志物,通过七折交叉验证方法来评价其预测效果及与CA125联合的诊断准确性.进一步采用cytoscape软件研究差异脂质物质间的相互作用.通过Wilcoxon秩和检验方法筛选出能够区分早晚期卵巢癌的生物标志物.结果 共筛选出20种可用于区分卵巢癌和对照的差异脂质生物标志物,其中Stearamide、Stearic acid、Arachidic acid和PI(42∶9)与CA125不相关(P＜0.05),这4个脂质与CA125联合AUC值为0.94,大于CA125单独的诊断性能.另外,其中8个差异脂质在早期与晚期上皮性卵巢癌患者中有差异,分别为PC(35∶4)、PC(38∶6)、PC(46∶4)、PC(P-35∶2)、PE(P-36∶6)、PG(34∶2)、Cer(d18∶1/16∶0)和3-Deoxyvitamin D3,均P值＜0.05.结论 卵巢癌血浆脂质组学筛选出的物质提高了CA125单独诊断的准确性,其中8个差异物质可以作为卵巢癌早期诊断潜在的生物标志物.     

晚期卵巢癌化疗中CA125下降的临床意义

Objective: The aim of this study was to compare the serum CA125 regression in advanced ovarian carcinoma patients treated with paclitaxel/platinum (TP) and platinum/epirubicin/ifosfamide (PAC) during early chemotherapy.The relationship between survival and CA125 regression during first line chemotherapy was evaluated.Methods: This retrospective TP or PAC chemotherapy, respectively.Only epithelial ovarian cancers were included.CA125 half-life was calculated by mono-compartmental logarithmic regression.Every patient's nadir CA125 concentration was also studied.T-test was used in comparing CA125 half-life and nadir CA125 between two groups.Survival analyses for progression-free survival (PFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox) models for all of the patients.Results: There was not significant difference in CA125 half-life and nadir CA125 concentration between two groups (P > 0.05).CA125 half-life and nadir CA125 concentration had a univariate prognostic value for PFS and OS (P < 0.0001) in all of the patients.However pre-chemotherapy CA125 and different chemotherapy agents were not prognostic factors for PFS and for OS (P > 0.05, for each).In Cox models, CA125 half-life (P = 0.0006), residual tumour (P < 0.0001), and nadir concentration (P = 0.0032) were significant prognostic factors for disease free survival (DFS).For OS, CA125 half-life (P = 0.0013), residual tumor (P < 0.0001), and nadir concentration (P = 0.0118) were also the significant prognostic factors.Conclusion: There isn't significant difference in serum CA125 regression between patients who are treated with PAC or PT during early chemotherapy.CA125 half-life and nadir CA125 concentration are independent prognostic factor in advanced ovarian cancer.     

93例复发性卵巢癌疗效分析

目的 预测卵巢癌易复发因素,分析复发性卵巢癌（ROC）患者的疗效与预后。方法 回顾性分析93例ROC患者的临床资料。采用单变量分析ROC患者无瘤生存期（DFI）影响因素。评估不同治疗方法对ROC患者无进展生存期（PFS）和复发后总生存时间（OS）的影响。结果 初次治疗后DFI单变量分析显示：肿瘤的组织分化程度、临床分期、初次术后残留肿瘤大小、初次手术后化疗疗程数与DFI有关（均P<0.05）。93例ROC患者中,手术组：44例患者行二次肿瘤细胞减灭术(SCS),并联合化疗和（或）靶向治疗;非手术组：49例患者行单纯化疗和（或）靶向治疗。手术组PFS和复发后OS均较非手术组有所延长;手术组中：CA125≤150 U/L的患者OS和PFS较CA125>150 U/L的患者均有所延长（均P<0.05）;术前影像学检查提示复发肿瘤个数≤3的患者术后OS和PFS较复发肿瘤个数>3的患者均有所延长（P<0.05）。结论 肿瘤病理分化程度越高、临床分期越早、初次术后残余病灶越小以及术后化疗疗程越规范足量的卵巢癌患者DFI越长、复发越晚。卵巢癌复发时CA125≤150 U/L、影像学检查复发肿瘤个数≤3的患者可能会从SCS术中获益。     

晚期卵巢癌化疗中CA125 下降的临床意义

目的:比较晚期卵巢癌TP方案和PAC 方案化疗血清CA125 下降情况。评价化疗中CA125 下降情况对晚期卵巢癌生存预后的预测作用。方法:122 例和95例Ⅱc～Ⅳ期卵巢癌患者肿瘤细胞减灭术后分别采用TP和PAC 方案化疗。每一个疗程化疗前取静脉血免疫法测定血清CA125,计算CA125 半衰期使用单项分割Log 减低法。t 检验用于比较两治疗组间CA125 半衰期和CA125 最低值间差异,应用单因素（Kaplan-Meier）和多因素Cox 回归分析全部患者化疗中CA125 下降情况对无进展生存和总生存期的意义。结果:两化疗组间CA125 半衰期和最低值间无显著性差异。单变量分析全部患者CA125 半衰期和最低值是无进展生存和总生存期的预后指标,而不同化疗方案及化疗前CA125 水平不是预后指标。多变量分析结果显示:CA125 半衰期,残存病灶,CA125 最低值是无进展生存和总生存期的独立预后指标。结论:晚期卵巢癌应用TP和PAC 方案化疗CA125 下降无显著性差异;一线化疗中CA125 半衰期和最低值是晚期卵巢癌独立的预后因素。      

血清α-羟丁酸脱氢酶联合糖类抗原125检测在卵巢癌诊断中的应用价值

目的探讨卵巢癌患者血清α-羟丁酸脱氢酶、糖类抗原125(CA125)在卵巢癌中的表达情况,分析二者联合检测对卵巢癌的诊断价值。方法选取40例卵巢癌患者、35例卵巢良性病变患者和40例健康者,分别命名为卵巢癌组、卵巢良性病变组、健康对照组。检测血清α-羟丁酸脱氢酶、CA125水平,探讨血清α-羟丁酸脱氢酶水平与卵巢癌患者病理特征的关系。绘制受试者工作特征(ROC)曲线,分析血清α-羟丁酸脱氢酶联合CA125检测对卵巢癌的诊断效能。结果卵巢癌组和卵巢良性病变组患者的血清CA125、α-羟丁酸脱氢酶水平均高于健康对照组受试者,卵巢癌组患者的血清CA125水平高于卵巢良性病变组患者(P﹤0.05)。不同分化程度、国际妇产科联盟(FIGO)分期和淋巴结转移情况的卵巢癌患者的血清α-羟丁酸脱氢酶水平比较,差异均有统计学意义(P﹤0.01)。ROC曲线分析结果显示,血清α-羟丁酸脱氢酶联合CA125检测鉴别诊断卵巢癌与卵巢良性病变的曲线下面积为0.834(95%CI:0.743~0.924),灵敏度和特异度分别为85.46%和90.02%;鉴别诊断卵巢癌与健康者的曲线下面积为0.958(95%CI:0.919~0.997),灵敏度和特异度分别为89.47%和95.83%。结论卵巢癌患者的血清α-羟丁酸脱氢酶和CA125水平较高,有一定的卵巢癌诊断价值,二者联合检测可提高对卵巢癌的诊断效能。     

CA125联合 CA19－9、CEA、CA72－4检测在上皮性卵巢癌诊断中的意义

目的：阐明联合检测糖类抗原（CA125、CA19－9、CA72－4）与癌胚抗原（CEA）在上皮性卵巢癌中的诊断意义。方法：对81例上皮性卵巢癌患者,81例良性卵巢肿瘤患者以及作为对照的80例健康体检者血清中的 CA125、CA19－9、CA72－4与 CEA 进行检测。采用 ROC 曲线及 AUC、Logistic 回归分析评估上述血清标记物对上皮性卵巢癌的诊断意义。结果：卵巢癌患者血清肿瘤标记物 CA125、CA19－9、CA72－4的水平与阳性率明显高于良性卵巢肿瘤以及对照组健康体检者（P ＜0．05）。ROC 曲线显示 CA125、CA19－9、CEA 与CA72－4曲线下面积分别为0．904±0．025、0．670±0．042、0．497±0．046 and 0．821±0．033。联合检测上述肿瘤标记物显示最高的敏感性（91．4％）与较好的特异性（83．9％）。与其他单一肿瘤标记物相比,CA125显示最高的敏感性与较好的特异性。结论：联合检测 CA125、CA19－9、CEA 与 CA72－4可以提高上皮性卵巢癌早期诊断的敏感性与准确性。     

Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

BACKGROUND:

When epithelial ovarian cancer is detected at an early stage (I‐II), the 5‐year survival rate is between 70% and 90%; whereas, when it is detected in late stages (III‐IV), the 5‐year survival rate slips to <30%. In a previous report, the authors observed that proteomic biomarkers and cancer antigen 125 (CA 125) exhibited a sensitivity of 84% at a specificity of 98% for identifying sera from patients who had stage I disease at the time of surgery, significantly improving the sensitivity of CA 125 alone. The challenge, however, is to detect ovarian cancer before clinical diagnosis. The current study was part of a large effort to compare different multimarker biomarker panels for the early detection of ovarian cancer. Several biomarkers were evaluated alone and in combination with CA 125 in prediagnostically collected sera from women in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

METHODS:

Proximal prediagnostic sera from 118 women with ovarian cancer (cases) and from 951 age‐matched women (controls) (8 controls per case, including 4 randomly selected from the general population, 2 with CA 125 levels ≥35 U/mL, and 2 with a positive family history of breast/ovarian cancer) were analyzed using the CA 125 immunoassay and surface‐enhanced laser desorption and ionization time‐of‐flight mass spectrometry to measure 7 proteins (apolipoprotein A1, truncated transthyretin, transferrin, hepcidin, β‐2 microglobulin, connective tissue activating protein III), and interalpha‐trypsin inhibitor heavy‐chain 4). Data were analyzed by 2 statistical strategies that combined the 7 markers and CA 125 into 1 predictive score for disease classification.

RESULTS:

CA 125 levels were elevated (≥35 U/mL) in 61.5% of 65 patients who had CA 125 data available from samples that were collected <12 months before cancer diagnosis; however, levels of the additional 7 biomarkers were not different between cases and the 3 control groups individually or combined. Two panels that combined CA 125 and the 7 biomarkers failed to improve the sensitivity of CA 125 alone.

CONCLUSIONS:

In contrast to earlier findings from analyzes of postdiagnostically collected sera, the addition of 7 biomarkers to CA 125 did not improve sensitivity for preclinical diagnosis beyond CA 125 alone. Cancer 2012;. © 2011 American Cancer Society.     

The use of kallikrein-related peptidases as adjuvant prognostic markers in colorectal cancer

Several members of the human tissue kallikrein-related peptidase (KLK) family are emerging cancer biomarkers. The aim of this study was to analyse the expression of a panel of KLKs in colorectal cancer and to find out if the multiparametric combination of them can increase the accuracy of prediction of patients survival beyond the traditional clinical information. Nine KLKs (KLK5-8, KLK10, KLK11, KLK13-15) were measured using ELISA assays in cytosolic extracts of 122 colon cancer tissues and their nearby normal mucosa, obtained during surgery. The mean levels of almost all KLKs in tumour tissues were significantly different from their counterparts of normal tissue (P<0.0001). KLK 5, 6, 7, 13, 14 were significantly associated with overall survival in univariate analysis, but after adjusting for age, TNM and differentiation stage, only KLK5 (HR: 1.24 (95% CI: 1.05–1.47)), KLK7 (HR: 1.57 (95% CI: 1.04–2.37)) and KLK14 (HR: 1.43 (95% CI: 1.05–1.94)) remained significant. Addition of a panel of selected KLK markers to clinical parameters gave an increment in AUC of 0.86 beyond the clinical factors at year 1, showing that it can increase the accuracy of prediction of overall survival beyond the traditional clinical information, particularly the short-term (1 year) survival after surgery.     

Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses

Background: Ovarian cancer remains a major worldwide health care issue due to the lack of satisfactory diagnostic methods for early detection of the disease. Prior studies on the role of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in detecting ovarian cancer presented conflicting results. New tools to improve the accuracy of identifying malignancy are urgently needed. We here aimed to evaluate the diagnostic utility of tissue CA125 and HE4 gene expression in comparison to serum CA125 and HE4 in discriminating benign from malignant pelvic masses. Materials and Methods: One-hundred Egyptian women were enrolled in this study, including 60 epithelial ovarian cancer (EOC) patients and 20 benign ovarian tumor patients, as well as 20 apparently healthy women. Preoperative serum levels of CA125 and HE4 were measured by immunoassays. Tissue expression levels of genes encoding CA125 and HE4 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The diagnostic performance of CA125 and HE4, measured either as mRNA or protein levels, was evaluated by receiver operating characteristic (ROC) curves. Results: The serum CA125+HE4 combination and serum HE4, with area under the curve (AUC) values of 0.935 and 0.932, respectively, performed significantly better than serum CA125 (AUC=0.592; P<0.001). Tissue CA125 and HE4 (AUC=1) performed significantly better than serum CA125 (P<0.001), serum HE4 (P=0.016) and the serum CA125+HE4 combination (P=0.018). Conclusions: Measurement of tissue CA125 and HE4 gene expression not only improves discriminatory performance, but also broadens the range of differential diagnostic possibilities in distinguishing EOC from benign ovarian tumors.