B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression

OBJECTIVE: This study characterizes the expression of the novel biomarker B7-H4 in ovarian cancer tissue, normal ovaries, and benign ovarian tumors, and evaluates its relationship to CA125. METHODS: Ovarian tissue lysates from 251 patients with ovarian carcinoma were assessed for the levels of B7-H4 and CA125 by ELISA assays. For comparison, ovarian tissues from patients with benign ovarian tumors (n=43) and patients with normal ovaries (n=32) were tested. The marker concentrations were correlated with CA125 expression, clinicopathological variables, and patient outcome. RESULTS: Using a cut-off based on the 95th percentile of B7-H4 or CA125 concentration in the control group, B7-H4 was over-expressed in 48% of patients with stage I cancer, 55% of patients with stage II cancer, and 67% of patients with late stage cancer. CA125 was elevated in 31% patients with early stage cancer. B7-H4 was elevated in tumors of 30 patients with early stage cancer that were negative for CA125. The combination of B7-H4 and CA125 identified 56 early stage cancer patients (65%) as positive. Correlation of marker expression to clinical outcome showed that high B7-H4 levels were correlated with poor prognosis. However, the effect was not significant when outcome was adjusted for other clinicopathological variables. CONCLUSION: B7-H4 expression was low in normal ovaries and in benign tumors while half of early stage and two-thirds of late stage cancers over-expressed B7-H4. The data are consistent with previous observations and support further investigation of B7-H4 in the detection of early stage ovarian cancer either alone, or in combination with CA125.     

CA125阴性卵巢癌血清标志物差异蛋白质组学的研究

目的:通过二维差异凝胶电泳(2-DEDIGE)和基质辅助激光解吸离子化-飞行时间(MALDI-TOF/TOF)串联质谱差异蛋白质组学方法寻找CA125阴性卵巢上皮癌血清标志物,以提高卵巢上皮癌诊断的灵敏度和特异度。方法:收集103例卵巢上皮癌,60例正常对照,63例卵巢良性肿瘤、63例盆腔良性病变的血清。按年龄匹配,选取6例CA125阴性卵巢癌和6例正常对照组的血清等容积混合。祛除血清高丰度白蛋白和IgG后进行2-DEDIGE。实验重复3次。通过DeCyder软件分析得出有显著差异的蛋白质点,MALDI-TOF/TOF鉴定差异蛋白质。分别用WesternBlot和ELISA方法验证获选的血清标志物。结果:(1)经2-DEDIGE实验得出有显著差异的蛋白质点41个,MALDI-TOF/TOF成功鉴定了其中的28个蛋白质点。上调最显著的蛋白质点为结合珠蛋白(haptoglo-bin,Hp),下调最显著的蛋白质为转铁蛋白(transferrin,Tf);(2)WesternBlot和ELISA验证结果显示,CA125阴性卵巢上皮癌血清Hp和Tf与正常对照有显著差异(P<0.001);(3)CA125+Hp+Tf联合检测(两者或两者以上阳性判断为阳性)诊断卵巢上皮癌的灵敏度和特异度高于CA125、Hp和Tf单独检测。结论:Hp和Tf是卵巢上皮癌血清中差异表达的蛋白质,可作为卵巢上皮癌的血清标志物。CA125+Hp+Tf联合检测有助于提高卵巢上皮癌诊断的灵敏度和特异度,有助于提高CA125阴性卵巢上皮癌的检出率。     

Combining CA 125 and SMR serum markers for diagnosis and early detection of ovarian carcinoma

OBJECTIVES: The serum tumor marker CA 125 is elevated in most clinically advanced ovarian carcinomas. Because these elevations may precede clinical detection by a year or more, CA 125 is potentially useful for early detection as part of an ovarian cancer screening program. However, CA 125 is often not elevated in clinically detected cancer and is frequently elevated in women with benign ovarian tumors. CA 125 may be more useful in conjunction with one or more other tumor biomarkers. Additional markers could play a role if, when used with CA 125, they identify some carcinomas missed by CA 125 (i.e., they improve sensitivity), rule out false positives (i.e., improve specificity), or are able to detect the same cancers earlier. METHODS: We have evaluated a composite marker (CM) that combines CA 125 and a previously described soluble mesothelin related (SMR) marker in sera from 52 ovarian cancer cases, 43 controls with benign ovarian tumors, and 220 normal risk controls who participated in a screening program, including 25 healthy women having two serum samples collected 1 year apart. CA 125, SMR, and CM were evaluated for their ability to identify clinical disease and for their temporal stability, which assesses their ability to obtain even greater sensitivity when used in a longitudinal screening program. RESULTS: CM has the best sensitivity, with specificity equal to CA 125. Importantly, CM has temporal stability at least as high as CA 125. CONCLUSION: The CM may outperform CA 125 alone in a longitudinal screening program as well as in a diagnostic setting.     

eIF-4E、OPN在上皮性卵巢癌患者血清中的表达及临床意义

目的:检测eIF-4E、OPN在上皮性卵巢癌患者血清中的表达,探讨eIF-4E、OPN作为肿瘤标志物,与CA125联合检测的临床意义。方法:采集卵巢上皮性癌46例,卵巢交界性上皮性肿瘤16例、卵巢良性上皮性肿瘤12例及健康妇女12例的血清标本,用双抗体夹心(ELISA)法检测血清标本中eIF-4E、OPN的浓度,血清CA125浓度用化学发光法检测。结果:卵巢恶性肿瘤组及交界性肿瘤组血清中eIF-4E、OPN、CA125的浓度明显高于卵巢良性肿瘤组及正常对照组。eIF-4E检测阳性率63.04%,OPN检测阳性率76.9%,CA125检测阳性率71.74%,eIF-4E和CA125联合检测阳性率93.48%,OPN和CA125联合检测阳性率89.13%,eIF-4E、OPN及CA125三者联合检测阳性率97.83%。Ⅲ、Ⅳ期卵巢癌患者血清中CA125、eIF-4E、OPN浓度明显高于Ⅰ、Ⅱ期。结论:eIF-4E、OPN可作为卵巢肿瘤标志物,用于卵巢癌早期诊断,与CA125联合检测有较高的临床应用价值。     

Biomarker discovery for ovarian cancer using SELDI-TOF-MS

OBJECTIVES: The purpose of this study is to discover potential biomarkers for the detection and monitoring of adjuvant chemotherapy for ovarian cancer. METHODS: Serum samples from ovarian cancers and non-cancer controls were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). To discover the possible diagnostic biomarker for ovarian cancer, a preliminary training set of spectra derived from 31 primary ovarian cancer patients, 16 patients with benign ovarian diseases, and 25 healthy women was used to develop a proteomic model that discriminated cancer from non-cancer effectively. A blind test set, including 43 new cases, was used to validate the sensitivity and specificity of this multivariate model. To explore treatment-induced serum protein change, the protein profiles generated from 16 postoperative patients before chemotherapy are compared with those obtained after chemotherapy. RESULTS: A Four-peak model was established in the training set that discriminated cancer from non-cancer with sensitivity of 90.8% and specificity of 93.5%. A sensitivity of 87.0% and a specificity of 95.0% for the blind test were obtained, compared with 60.7%, 55% for CA125 for the same samples. These 4 markers performed significantly better than the current standard marker, CA125 (P < 0.05). One protein peak (mass/charge ratio [m/z], 4,475) was identified in 12 of 16 (75%) postoperative patients after chemotherapy, but was absent before chemotherapy. CONCLUSION: The proteins represented by these peaks are candidate biomarkers for ovarian cancer diagnosis and/or monitoring treatment response.     

A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer

A number of members of the B7 superfamily of ligands have been implicated in tumor immunogenicity and cancer development. Two of these recently characterized ligands, B7-H4 and B7-H3, have been linked to ovarian tumors. B7-H4 is consistently overexpressed in ovarian tumor specimens, and its tissue and serum levels have been found to be a potential biomarker for ovarian cancer, either alone or in combination with CA125. More recently, B7-H3 has been found to be overexpressed in a large series of ovarian cancer tumor specimens and similar to other types of carcinomas, B7-H3 overexpression has been correlated with poor survival. On the basis of the results obtained by knocking down B7-H3 protein using siRNA, researchers have suggested that blocking the action of B7-H3 could reduce tumor growth, metastatic potential, and improve survival. Because siRNA knock-down is not an ideal clinical therapeutic vehicle, additional studies using antibody-mediated suppression of the B7-H3 protein are necessary to fully evaluate the clinical potential of this molecule as a therapeutic target.     

术前测定血清CA125、CA199、CA724、CEA和GM-CSF在鉴别附件包块性质中的作用

探讨术前测定患者血清CA12 5、CA19 9、CA72 4、CEA和GM -CSF水平在鉴别附件包块良恶性质中的作用。方法 :74例附件包块患者术前 1周内采外周血 ,用固相免疫放射法测定各种肿瘤标志物浓度 ,并与术后组织学诊断比较。计算各标志物单独和联合应用诊断卵巢癌的相应诊断参数。结果 :( 1)CA12 5(临界值 70U/ml)鉴别卵巢肿瘤性质的敏感性和特异性分别为 85 71%和 82 61% ,CA19 9(临界值 30U/ml)分别为 4 2 86%和 73 33% ,CA72 4 (临界值 3 8U/ml)分别为 53 57%和 90 90 % ,CEA(临界值 5ng/ml)分别为 4 6 4 3%和 4 8 89% ;( 2 )联合应用肿瘤标志物 :CA12 5联合CA19 9的敏感性和特异性分别为 89 2 9%和 73 33% ;CA12 5联合CA72 4的敏感性和特异性分别为 89 2 9%和 75 56% ;CA12 5联合CEA的敏感性和特异性分别为 92 86%和 4 0 0 0 % ;( 3)如果去除 9例子宫内膜异位症 ,CA12 5、CA19 9、CA72 4和CEA的特异性分别增至 89 19% ,80 55% ,94 2 9%和4 7 2 2 %。结论 :此项研究应用的肿瘤标志物中以CA12 5最为敏感。将CA12 5临界值定为 70U/ml时诊断效果最佳。CA72 4的特异性最高 ,但诊断卵巢癌的敏感性低。CEA的诊断价值有限 ,GM -CSF则无价值。CA12 5与其他肿瘤标志物联合检测时诊断的特异性会部分丧失。?     

Comparison of candidate serologic markers for type I and type II ovarian cancer

Objective

To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers.

Methods

Levels of 14 currently promising ovarian cancer-related biomarkers, including CA125, macrophage inhibitory factor-1 (MIF-1), leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II (IGF-II), autoantibodies (AAbs) to eight proteins: p53, NY-ESO-1, p16, ALPP, CTSD, B23, GRP78, and SSX, were measured in the plasma of 151 ovarian cancer patients, 23 with borderline ovarian tumors, 55 with benign tumors and 75 healthy controls.

Results

When examined individually, seven candidate biomarkers (MIF, Prolactin, CA-125, OPN, Leptin, IGF-II and p53 AAbs) had significantly different plasma levels between type II ovarian cancer patients and healthy controls. Based on the receiver operating characteristic (ROC) curves constructed and area under the curve (AUC) calculated, CA125 exhibited the greatest power to discriminate the plasma samples of type II cancer patients from normal volunteers (AUC 0.9310), followed by IGF-II (AUC 0.8514), OPN (AUC 0.7888), leptin (AUC 0.7571), prolactin (AUC 0.7247), p53 AAbs (AUC 0.7033), and MIF (AUC 0.6992). p53 AAbs levels exhibited the lowest correlation with CA125 levels among the six markers, suggesting the potential of p53 AAbs as a biomarker independent of CA125. Indeed, p53 AAbs increased the AUC of ROC curve to the greatest extent when combining CA125 with one of the other markers. At a fixed specificity of 100%, the addition of p53 AAbs to CA125 increased sensitivity from 73.8% to 85.7% to discriminate type II cancer patients from normal controls. Notably, seropositivity of p53 AAbs is comparable in type II ovarian cancer patients with negative and positive CA125, but has no value for type I ovarian cancer patients.

Conclusions

p53 AAbs might be a useful blood-based biomarker for the detection of type II ovarian cancer, especially when combined with CA125 levels.     

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer

Objective

The low prevalence of ovarian cancer demands both high sensitivity (> 75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers.

Methods

Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls.

Results

In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P = 0.015, McNemar's test).

Conclusion

Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer.     

血清CA125结合B超对绝经后妇女卵巢恶性病变的预测价值

目的 通过了解绝经后妇女卵巢肿物的临床特点，探讨早期发现绝经后妇女卵巢恶性肿瘤的可行方法。方法 回顾分析302例经手术后病理证实为卵巢肿物的自然绝经后妇女的临床特点，采用B超结合血CA125的定量测定。结果 71．2％的绝经后卵巢肿物患者无自觉症状，38．7％为卵巢恶性肿瘤，BUS结合血CA125对卵巢恶性病变预测的敏感性为98．4％，特异性为57．9％，阳性预测值62．6％，阴性预测值98．1％。结论 对绝经后妇女实施妇科检查及B超的筛查结合血CA125的定量测定，有助于临床医生及时发现卵巢恶性肿瘤。     

Evaluation of HE4 as an extrabiomarker to CA125 to improve detection of ovarian carcinoma: is it time for a step forward?

Purpose

To evaluate human epididymis protein 4 (HE4) as an extrabiomarker to cancer antigen 125 (CA125) to improve the detection of ovarian carcinoma.

Methods

Sixty patients with ovarian carcinoma, 50 patients with benign ovarian tumors and 30 healthy women were included in the present study. Serum concentration of HE4 was assayed using ELISA technique, while CA125 was assayed using chemiluminescent enzyme immunoassay.

Results

The median CA125 and HE4 serum values were significantly higher among ovarian cancer patients when compared with healthy control However, the median serum levels of CA125 but not HE4 were significantly higher among patients with benign ovarian tumors as compared to healthy women. Based on the receiver operator characteristics curve analysis, HE4 had higher sensitivities than CA125 for the detection of ovarian cancer at 90, 95 and 98 % specificities and the combination of both markers yielded a higher sensitivity than either alone. However, CA125 but not HE4 had higher sensitivities for the detection of benign ovarian tumors at the same specificities. In addition, a positive correlation was observed between HE4 and CA125 among patients with ovarian carcinoma.

Conclusion

HE4 is a valuable marker for ovarian cancer diagnosis and when combined with CA125, they had a higher sensitivity at a set specificity, thus providing a more accurate predictor of ovarian cancer than either alone.     

Potential markers that complement expression of CA125 in epithelial ovarian cancer

BACKGROUND: When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can be cured with surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection. METHODS: From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues. RESULTS: Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUC1. CONCLUSIONS: At the level of tissue expression, each of 10 potential serum markers could be detected in 29-100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum.     

CA125在卵巢癌诊断中的应用困境与突破

CA125是应用最广泛的卵巢癌血清标志物。但近年来发现其诊断特异度较低,不少良性疾病患者及妊娠期或月经期妇女血清CA125也明显升高。这一状况给卵巢癌术前诊断及人群筛查带来诸多困扰。鉴于CA125分子是一种高度糖基化的黏蛋白,其糖基化修饰在卵巢癌中具有明显的特征结构,近期研究证实被特征性糖链所修饰的CA125亚型将有助于提高卵巢癌诊断准确度,有望突破上述困境。     

Evaluation of selected serum protein markers as early detectors of ovarian cancer

OBJECTIVE: an attempt to determine the value of the simultaneous quantization of osteopontin (OPN), insulin-growth factor II (IGF II), leptin, prolactin and CA 125 for early detection of ovarian cancer. MATERIALS AND METHODS: Prospective study of 69 women including: 15 females with ovarian cancer; 33 females with benign ovarian neoplasm; 21 disease-free females; The levels of IGF II, prolactin, leptin and CA 125 were determined in serum, while the level of OPN was checked in plasma. RESULTS: The concentrations of IGF II, leptin and prolactin do not let us distinguish among disease-free females, females with ovarian cancer and those with benign ovarian neoplasms on the basis of biochemical markers. The comparison of OPN and CA 125 levels showed significant differences in the concentrations of the biomarkers between disease-free females and females with ovarian cancer, as well as between females with benign ovarian neoplasms and females with ovarian cancer. The ROC curves for two groups: disease-free females and females with ovarian cancer, proved the diagnostic value of OPN and CA 125. CONCLUSIONS: The simultaneous quantization of OPN, IGF II leptin and prolactin has not been proved useful for the early detection of ovarian cancer. Statistically significant increase of OPN & CA 125 levels was noted in case of women with ovarian cancer diagnosed through microscopic examination. The analysis of ROC curves showed comparable diagnostic usefulness of both markers. Quantization of OPN may have an additional value for treatment monitoring of women diagnosed with ovarian cancer but with concentration of CA 125 within the reference value.     

应用多项肿瘤标记物检测卵巢恶性肿瘤的研究

目的为了提高卵巢恶性肿瘤诊断的特异性及敏感性,加强术后患者的病情追踪。我们应用５项肿瘤标记物ＳＡ,ＬＳＡ,ＣＡ１２５,ＣＰ２,６Ｂ１１Ａｂ２进行临床观察。方法对６７例卵巢恶性肿瘤及３３例卵巢良性肿瘤患者进行血清检测,以３８例正常妇女进行对照。结果单纯应用ＣＡ１２５诊断卵巢恶性肿瘤的敏感性及特异性分别为８３６％及８５９％,而５项肿瘤标记物中以任意３项及３项以上阳性为标记物诊断阳性时,检测卵巢恶性肿瘤的敏感性及特异性分别为８６６％及９４４％。临床Ⅰ、Ⅱ期患者的５项肿瘤标记物联合检测的特异性及敏感性,较ＣＡ１２５单项检测有明显提高。结论５项肿瘤标记物联合检测,对提高卵巢恶性肿瘤诊断的准确性及术后监测有一定意义     

Combination assay of CA125, TPA, IAP, CEA, and ferritin in serum for ovarian cancer

The levels of CA125, TPA, IAP, CEA, and ferritin in the serum were measured simultaneously in 68 healthy nonpregnant females and 133 patients with various gynecological diseases, and were subjected to statistical discriminant analysis for the diagnosis of ovarian cancer. The usefulness and the limits for diagnosis of various gynecological diseases were investigated for each tumor marker. Also, the diagnostic usefulness of the stepwise discriminant analysis employing the values of these five tumor markers in the serum in cases of ovarian cancer was compared with that of CA125 measurements alone. Because the frequency of cases with an elevated serum CA125 level increased more specifically in the ovarian cancer group than those of other tumor makers in the serum, this parameter was considered to be more useful for the diagnosis of ovarian cancer than the levels of the other tumor markers. The frequencies of cases with the elevated serum CA125 levels, however, also increased in the groups of patients with endometriosis and at an early stage of normal pregnancy more than in the group of healthy nonpregnant females. In the ovarian cancer patients, the discriminant analysis employing the values of CA125 and four other tumor markers in sera was more useful for early diagnosis, differential diagnosis, early detection of recurrences, and the determination of complete remission after therapy than the measurement of the serum CA125 level alone.     

检测原发性卵巢癌和转移性卵巢癌CDX2、CK7、CA_(125)表达的临床意义

目的:通过检测卵巢原发性上皮性癌和卵巢转移性结直肠腺癌中尾型同源盒转录因子2(CDX2)、细胞角蛋白7(CK7)、糖链抗原125(CA_(125) )的表达情况,探讨其临床意义。方法:选取卵巢原发性上皮性癌82例,原发性结直肠腺癌50例,卵巢转移性结直肠腺癌35例,通过免疫组化法检测CDX2、CK7、CA_(125) 的表达情况并进行分析比较。结果:CDX2在原发性结直肠腺癌和卵巢转移性结直肠腺癌中的阳性表达率(分别为100.0%和85.7%)明显高于卵巢原发性上皮性癌(13.4%),差异有统计学意义(P0.001)。CK7、CA_(125) 在卵巢原发性上皮性癌中的阳性表达率(分别为57.3%和73.2%)明显高于原发性结直肠腺癌(分别为26.0%和4.0%)和卵巢转移性结直肠腺癌(分别为22.9%和5.7%),差异有统计学意义(P0.001)。卵巢原发性上皮性癌联合检测CK7、CA_(125) 的阳性表达率(91.5%)高于单个指标(CA_(125) 为73.2%,CK7为57.3%),差异有统计学意义(P0.001)。结论:卵巢原发性上皮性癌中CK7和CA_(125) 高表达,可作为其抗体检测指标。CK7和CA_(125) 联合检测可提高卵巢原发性上皮性癌的检出率。     

Elevated serum levels of macrophage colony-stimulating factor and OVX1, 11 months prior to the diagnosis of stage IC ovarian cancer

In published trials, CA125 has been utilized to trigger ultrasound examination for the early detection of ovarian cancer. Although serum CA125 levels can be elevated prior to clinical detection of ovarian cancer, only approximately half of patients with stage I disease will have an abnormal value. A combination of CA125, macrophage colony-stimulating factor (M-CSF) and the mucin marker OVX1 will detect> 95% of stage I patients, but it is not known whether the markers can be elevated prior to clinical detection of the disease. A postmenopausal patient was found to have small unilocular bilateral cystic adnexal lesions during an abdominal ultrasound examination. No pelvic abnormality could be palpated. Serum levels of the CA125 antigen were within the normal range. Progressive ultrasound changes prompted a laparotomy II months later, and the diagnosis of a stage IC serous cystadenocarcinoma of the ovary was established. A retrospective analysis of stored serum samples revealed that this patient had elevated serum levels of M-CSF and OVX1 at the time of the original ultrasound scan. Interpreted within the context of a potential screening strategy for ovarian cancer, these data illustrate that either or both of these tumor markers and/or ultrasound could have identified this ovarian cancer many months prior to the actual diagnosis, while the disease was at an early stage.     

LPA、CA125与经阴道彩色多普勒超声联合诊断卵巢上皮癌的临床价值

目的:探讨血浆溶血磷脂酸(LPA)在卵巢上皮癌患者血浆中的表达水平,及其与血清CA125和经阴道彩色多普勒超声(TV-CDUS)联合应用诊断卵巢上皮癌的临床价值。方法:术前检测卵巢上皮癌48例,卵巢良性肿瘤30例的LPA、CA125,以20例健康者作为对照,卵巢肿瘤患者同时经阴道超声评分和TV-CDUS检查。结果:卵巢癌患者LPA水平明显高于卵巢良性肿瘤组和健康对照组,差异有统计学意义(P0.05),LPA水平在良性肿瘤组与健康对照组之间无显著差异(P0.05)。单独应用LPA、CA125、TV-CDUS检测诊断卵巢癌的敏感性和特异性分别为87.5%、79.16%、81.25%和80%、70%、86%,各组间敏感性和特异性比较,无显著差异(P0.05)。LPA、CA125、TV-CDUS 3项联合检测诊断卵巢癌的敏感性和特异性为95.80%和94%,与单独应用CA125检测特异性比较,差异有统计学意义(P0.05)。LPA诊断卵巢癌的敏感性和特异性与卵巢癌分期和病理类型无关(P0.05),CA125诊断卵巢癌的敏感性和特异性与卵巢癌的分期和病理类型有关(P0.05)。结论:卵巢上皮癌患者血浆LPA水平明显升高,有望成为卵巢上皮癌诊断的敏感指标,联合检测血浆LPA、血清CA125与TV-CDUS有助于术前卵巢癌的诊断。     

主动循环热灌注化疗对卵巢癌腹水疗效及HE4、CA125、VEGF和B7-H4水平的影响

目的 探讨卵巢癌腹水患者采用主动循环腹腔热灌注化疗治疗的效果及对血清肿瘤相关标记物水平的影响.方法 选取84例卵巢癌伴腹水患者,根据腹腔热灌注化疗方法分为主动循环组和常规组各42例,两组患者采用紫杉醇+顺铂实施不同的腹腔热灌注治疗.结果 主动循环组与常规组进入腹腔时的灌注液体温度差异无统计学意义(P>0.05),抽出腹...