血清中肿瘤相关抗原自身抗体谱与CA125联合检测在卵巢恶性肿瘤诊断及病情监测中的价值

目的 评价血清中肿瘤相关抗原自身抗体谱与CA125联合检测在卵巢恶性肿瘤诊断及病情监测中的价值.方法 选择2003年8月23日至2006年3月28日间广西医科大学附属肿瘤医院收治的卵巢恶性肿瘤患者126例(均为治疗前)、卵巢良性肿瘤患者42例,以及2003年至2006年在本院进行健康体检证实无肿瘤及免疫性和炎症性疾病的健康妇女142例,用间接ELISA法检测其血清中肿瘤相关抗原(即TM4SF1、C1D、TIZ、OV-142、FXR1、OV-189)的IgG、IgM型自身抗体,用二分类logistic回归法分析由上述自身抗体组成的自身抗体谱与CA125联合检测在卵巢恶性肿瘤诊断中的价值.另选择同期收治的24例卵巢恶性肿瘤患者,检测其治疗前、后肿瘤相关抗原自身抗体谱的变化,验证并分析自身抗体谱在卵巢恶性肿瘤病情监测中的价值.结果 卵巢恶性肿瘤患者(126例)血清中肿瘤相关抗原IgG型自身抗体的阳性率为34.1%～47.6%,非卵巢恶性肿瘤患者(184例,包括卵巢良性肿瘤患者42例和健康妇女142例)为13.0%～19.0%,两者比较,差异有统计学意义(P＜0.05);卵巢恶性肿瘤患者血清中肿瘤相关抗原IgM型自身抗体的阳性率为39.7%～53.2%,非卵巢恶性肿瘤患者为12.0%～33.2%,两者比较,差异有统计学意义(P＜0.05).FXR1抗原IgG型自身抗体及TIZ、FXR1、OV-189抗原IgM型自身抗体在早期(Ⅰ～Ⅱ期)卵巢恶性肿瘤患者血清中的阳性率(分别为55.3%、63.8%、61.7%、66.0%)明显高于晚期(Ⅲ～Ⅳ期)患者(分别为34.2%、39.2%、26.6%、45.6%),差异有统计学意义(P＜0.05).由TM4SF1、C1D、FXR1抗原IgG型自身抗体及TM4SF1、TIZ抗原IgM型自身抗体组成的自身抗体谱,该抗体谱检测的敏感度为75.4%、特异度为78.3%、准确率为77.1%,与CA125单独检测(分别为61.1%、88.0%、77.1%)比较,其敏感度明显增高(P＜0.05)、特异度明显降低(P＜0.05)、准确率相当,但自身抗体谱单独检测诊断早期卵巢恶性肿瘤患者的敏感度(76.6%)明显高于CA125单独检测者(51.1%,P＜0.05);自身抗体谱与CA125联合检测诊断卵巢恶性肿瘤的敏感度为85.7%、特异度为90.8%、准确率为88.7%,均明显高于自身抗体谱单独检测(P＜0.05);而与CA125单独检测比较,其敏感度和准确率明显升高(P＜0.05),特异度稍升高(P＞0.05).24例卵巢恶性肿瘤患者治疗后血清自身抗体谱与CA125联合检测的阳性率为42%(10/24),明显低于治疗前的88%(21/24,P＜0.05).结论 自身抗体谱与CA125联合检测可提高卵巢恶性肿瘤的早期诊断率,并可用于病情监测.

Abstract：

Objective To evaluate the clinical value of autoantibody spectrum against ovarian cancer associated antigens combine CA125 in detecting and monitoring ovarian cancer. Methods Circulating IgG, IgM autoantibodies against ovarian cancer associated antigens which included TM4SF1, C1D,TIZ, OV-142,FXR1 and OV-189 were measured by indirect ELISA in serum from 126 patients with ovarian cancer (prior treatment), 42 patients with benign ovarian masses, 142 healthy women. Cut off value of IgG, IgM autoantibodies were determined by receive operating characteristic (ROC) curve. CA125 was measured in serum by immunoradiometric assay (IRMA). We evaluated the clinical value of combining multiple autoantibodies (autoantibody spectrum ), combining autoantibody spectrum with CA125 by binary logistic regresion. The positive ratio of autoantibody spectrum in serum (prior and post treatment ) of 24 synchronization patients with ovarian cancer was analyzed to evaluate the value in monitoring state of illness.Results Our data indicated that serum contains IgG, IgM autoantibodies against ovarian cancer associated antigens. The positive ratio of IgG autoantibodies in serum from ovarian cancer patients and cancer-free patients were 34. 1% - 47. 6% and 13.0% - 19. 0%, respectively ( P ＜ 0. 05 ). The positive ratio of IgM autoantibodies in serum from ovarian cancer patients and cancer-free patients were 39. 7% - 53.2% and 12. 0% -33.2%, respectively (P ＜0. 05). The positive ratio of IgG autoantibodies against FXR1 and IgM autoantibodies against TIZ,FXR1 and OV-189 in early stage ( Ⅰ - Ⅱ ) ovarian cancer(55.3% ,63.8%,61.7% and 66. 0% ) were significantly higher than those in advanced ( Ⅲ - Ⅳ )ovarian cancer( 34. 2%,39. 2% ,26. 6% ,45.6%; all P ＜ 0. 05 ). Combining five autoantibodies ( TM4SF1 IgG, TM4SF1 IgM, C1D IgG, FXR1 IgG and TIZ IgM ) showed significantly improved sensitivity (75.4%, P ＜ 0. 05 ), lower specificity (78. 3% ,P ＜ 0. 05 ) and similar accuracy (77. 1%, P ＞ 0. 05 ) in detecting ovarian cancer compared to those of CA125 (61.1% ,88.0% ,77. 1% ). But the autoantibody spectrum showed significantly improved sensitivity in classifying early stage (76. 6% ), compared to those of CA125 (51.1% ,P ＜ 0. 05 ).Combining autoantibody spectrum with CA125 showed significantly improved sensitivity ( 85.7% ), specificity (90. 8% )and accuracy (88.7%) in detecting ovarian cancer compared to those of autoantibody spectrum alone ( all P ＜ 0. 05 ), while CA125 ( 61.1%, P ＜ 0. 05; 88. 0%, P ＞ 0. 05; 77. 1%, P ＜ 0. 05 ). The positive ratio of combine the autoantibody spectrum with CA125 was significantly lower in 24 post-treatment serum (42%) compared to the pairing prior treatment serum ( 88%, P ＜ 0. 05 ). Conclusion Combining the autoantibody spectrum against ovarian cancer associated antigens with CA125 can improve sensitivity,specificity and accuracy in detecting early ovarian cancer and may be used to monitoring state of illness.     

血清人附睾分泌蛋白4和CA125水平检测在卵巢恶性肿瘤中的诊断价值

目的 探讨血清人附睾分泌蛋白4(HE4)和CA125水平检测在卵巢恶性肿瘤诊断中的价值.方法 用酶联免疫吸附试验方法 对卵巢恶性肿瘤组(30例)、盆腔良性疾病组(110例,其中卵巢良性肿瘤45例、子宫内膜异位症和子宫腺肌病57例和盆腔炎8例)和正常组(137例)妇女血清中HFA和CA125水平进行双盲检测,结果 以中位数表示,分析两指标单独或联合检测诊断卵巢恶性肿瘤的价值.血清HF4和CA125正常值分别为0～150 pmoVL和0～35 kU/L,单独或联合检测时,其中任一指标高于正常值即定为阳性.结果 (1)卵巢恶性肿瘤组血清HE4和CA125水平分别为244 pmol/L 和601 kU/L,分别与盆腔良性疾病组(分别为32 pmoVL和22 kU/L)和正常组(分别为32 pmol/L和11 kU/L)比较,差异均有统计学意义(P<0.05).卵巢恶性肿瘤组血清HE4单项检测的阳性率为63.3%,明显低于血清CA125项榆测的阳性率(86.7%,P=0.036).(2)单项检测时,以盆腔良性疾病组作参照人群时,HE4和CA125单项检测的受试者工作特征曲线下面积(ROC-AUC)分别为0.900和0.840,其特异度为100%时的敏感度分别为70%和7%,两者比较,差异有统计学意义(P=0.000);以正常组作参照人群时,HE4和CAl25单项检测的ROC-AUC分别0.904和0.914,其特异度为100%时的敏感度分别为67%和87%,两者比较,差异有统计学意义(P=0.031).(3)联合检测时,以盆腔良性疾病组作参照人群时,HE4+CA,笛联合检测和CA125单项检测的ROC-AUC分别为0.894和0.840,其特异度为100%时的敏感度分别为50%和7%,两者比较,差异有统计学意义(P=0.000).以正常组作参照人群时,HE4+CA125联合榆测和HE4单项检测的ROC-AUC分别为0.914和0.904,其特异度为100%时的敏感度分别为87%和67%,两者比较,差异有统计学意义(P=0.031).以盆腔良性疾病组作参照人群时,HE4+CA125联合检测在特异度为100%时的敏感度(50%)虽然低于HE4单项检测(70%),但两者比较,差异无统计学意义(P=0.070).(4)以ROC曲线最左上方的点86 pmol/L、正常组95%参考值50 pmoVL和正常值的上限150 pmol/L为界值点,比较HE4单项检测对卵巢恶性肿瘤的诊断能力,结果 显示,界值点为50 pmol/L时的特异度和阳性预测值分别为95%和63%,明显低于界值点为86(分别为100%和95%)和150 pmoVL(均为100%)时的特异度和阴性预测值(P<0.01).结论 HE4单项检测诊断卵巢恶性肿瘤的特异度优于CA125单项检测,两者联合检测可以提高诊断能力.以150 pmol/L为界值点,对卵巢恶性肿瘤的诊断正确率更高,而以86 pmol/L为界值点有利于卵巢恶性肿瘤的筛查、降低漏诊率.     

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。     

恶性肿瘤特异性生长因子在卵巢肿瘤中的临床应用价值

目的探讨血清恶性肿瘤特异性生长因子(TSGF)在卵巢恶性肿瘤的诊断及疗效监测中的临床应用价值。方法使用TSGF快速诊断试剂盒,对170例患者的196份血清进行检测,其中69例为卵巢恶性肿瘤,18例卵巢交界性肿瘤,42例卵巢良性肿瘤,41例盆腔良性病变;同时取20例正常妇女血清标本作为对照。所有标本同时检测CA125。结果卵巢恶性肿瘤组血清TSGF阳性率明显高于其他各组(P<0.01)。晚期肿瘤的血清TSGF诊断敏感性高于早期(P<0.05)。卵巢高分化恶性肿瘤及交界性肿瘤血清TSGF敏感性明显低于中、低分化组(P<0.01)。TSGF诊断卵巢恶性肿瘤的敏感性和特异性分别为78.3％和48.2％,CA125为73.9％和55.4％,二者差异无显著性(P>0.05)。TSGF+CA125联合检测诊断卵巢恶性肿瘤的敏感性为87.0％,较TSGF、CA125单项检测敏感性明显提高(P<0.05),治疗前后血清TSGF水平下降不明显(P>0.05)。TSGF对卵巢恶性肿瘤的疗效监测价值似乎不大。结论 TSGF测定诊断卵巢恶性肿瘤的敏感性和特异性分别为78.3％和48.2％,其水平与细胞分化、临床分期有关。TSGF和CA125联合检测可明显提高卵巢恶性肿瘤的检出率,但TSGF对卵巢恶性肿瘤的疗效监测似无明显临床价值。     

人附睾分泌蛋白4联合CA125在卵巢恶性肿瘤与子宫内膜异位症鉴别诊断中的价值

目的 探讨血清人附睾分泌蛋白4(HE4)联合CA125水平检测在卵巢恶性肿瘤与子宫内膜异位症鉴别诊断中的价值.方法 采用酶联免疫吸附试验(ELISA)检测卵巢子宫内膜异位囊肿(内异症组)46例、卵巢上皮性癌(卵巢癌组)36例、卵巢非内膜异位良性肿瘤(良性肿瘤组)60例和健康妇女(对照组)50例血清中HE4和CA125水平,结果以中位数表示.血清HFA和CA125正常值分别为0～150 pmo/L和0～35 kU/L,单独或联合检测时,其中任一指标高于正常上限即定为阳性.通过制作受试者工作特征(ROC)曲线,以曲线下面积(AUC)反映诊断的准确性;以Mann-Whitney U 检验及相关性分析探讨两项指标单独或联合检测用于诊断卵巢内异症囊肿的价值.结果 (1)HE4水平:内异症、对照、良性肿瘤组妇女血清HE4水平分别为52.4、51.0、50.0 pmoL/L,3组比较,差异无统计学意义(P>0.05),卵巢癌组患者HE4水平为507.5 pmoL/L,与其他3组分别比较,差异均有统计学意义(P<0.05).(2)CA125水平:卵巢癌、内异症、良性肿瘤及对照组妇女血清CA125水平分别为743.0、84.9、15.4、11.5 kU/L,卵巢癌组与其他3组比较,差异均有统计学意义(P<0.05).(3)单项榆测结果:卵巢癌组以内异症组为参照时,HE4和CA125笛单项检测的AUC分别0.933和0.821,其特异度为95%时的敏感度分别为79.6%和49.0%;内异症组以对照组为参照时的AUC为0.453;以良性肿瘤组为参照时的AUC为0.496.(4)联合检测结果:卵巢癌组以内异症组为参照时,HE4联合CA125检测的AUC为0.936,其特异度为95%时的敏感度为81.0%.结论 HE4水平可作为卵巢内异症囊肿的鉴别诊断依据之一,HE4联合CA125水平检测能有效鉴别卵巢内异症囊肿和卵巢恶性肿瘤.     

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。     

AGR2在卵巢上皮性癌患者血清及癌组织中的表达及意义

目的:探讨卵巢上皮性癌血清和癌组织中人前梯度蛋白2(AGR2)的表达水平与卵巢上皮性癌发生、发展的关系及用于其诊断的意义.方法:采用ELISA法和电化学发光法检测40例卵巢上皮性癌、10例卵巢交界性肿瘤、20例卵巢良性肿瘤及17例健康体检者血清AGR2、CA125水平;采用免疫组化法检测各种卵巢肿瘤组织及因宫颈癌切除卵巢的15例正常卵巢组织中AGR2的表达情况,并结合临床病理参数进行分析.结果:①卵巢上皮性癌及卵巢交界性肿瘤组织AGR2的阳性表达率明显高于卵巢良性肿瘤及正常卵巢组织(P ＜0.05,P＜0.01).②卵巢上皮性癌及卵巢交界性肿瘤血清中AGR2水平明显高于卵巢良性肿瘤及健康体检者(P＜0.05).③卵巢上皮性癌血清AGR2水平及癌组织中AGR2的阳性表达率均与临床分期及淋巴结转移相关.④联合检测血清AGR2和CA 125曲线下面积与单独检测CA125、AGR2比较,差异均无统计学意义(P均＜0.05).结论:AGR2与卵巢上皮性癌的发生、发展有关.联合检测血清AGR2和CA 125对卵巢上皮性癌的早期诊断有参考价值.     

卵巢上皮性癌相关抗原的筛选和血清学检测

目的构建卵巢上皮性癌（卵巢癌）腹水肿瘤细胞的cDNA文库，从中筛选能用于卵巢癌早期诊断和免疫治疗靶点的卵巢癌相关抗原。方法用3例卵巢浆液性囊腺癌、1例卵巢黏液性囊腺癌、1例卵巢子宫内膜样癌患者的腹水肿瘤细胞构建cDNA文库，采用改良的重组克隆表达抗原的血清学鉴定（SEREX）技术与抑制性消减杂交（SSH）方法相结合的策略从文库中筛选卵巢癌相关抗原基因，并对其进行酶切鉴定、核苷酸测序分析。采用重组肿瘤抗原的微型血清学检测（SMARTA）法检测筛选出的卵巢癌相关抗原与96例卵巢癌患者和96例正常妇女的血清中相应自身抗体的阳性反应情况。结果经两轮血清学筛选和核苷酸测序分析，最终得到55个候选的卵巢癌相关抗原基因片段，代表45个基因，分为6类：（1）与已知的卵巢癌相关基因同源的基因，如BARD1基因等；（2）与其他肿瘤相关基因同源的基因，如TM4SF1基因等；（3）在一些特殊组织中表达的基因，如ILF3、FXR1基因等；（4）与一些特殊功能蛋白基因同源的基因，如TIZ、C1D基因等；（5）与胚胎来源的基因同源的基因，如PKHD1基因等；（6）其余为在基因库GenBank中无同源序列可比对的未知基因，如OV-189基因等。TM4SF1、C1D、BARD1、FXR1、OV-189基因的噬菌体重组融合抗原与卵巢癌患者血清中相应IgG型自身抗体反应的阳性率分别为28％、21％、23％、23％、31％，与正常妇女血清反应的阳性率分别为9％、6％、5％、8％、13％，分别比较，差异均有统计学意义（P〈0．01）；TIZ、FXR1、OV-189基因的重组抗原与卵巢癌患者血清中相应IgM型自身抗体反应的阳性率分别为26％、28％、18％，与正常妇女血清反应的阳性率分别为8％、11％、7％，分别比较，差异均有统计学意义（P〈0．05）。FXR1、OV-189基因的重组抗原与Ⅰ～Ⅱ期卵巢癌患者血清中相应IgG型自身抗体反应的阳性率（分别为34％、46％）高于Ⅲ～Ⅳ期者（分别为16％、23％），两者分别比较，差异均有统计学意义（P值分别为0．045、0．021）；OV-189基因的重组抗原与高分化卵巢癌患者血清中相应IgG型自身抗体反应的阳性率（为67％）高于中～低分化者（为26％），两者比较，差异均有统计学意义（P=0．001）。TIZ、FXR1基因的重组抗原与Ⅰ～Ⅱ期卵巢癌患者血清中相应IgM型自身抗体反应的阳性率（分别为40％、46％）高于Ⅲ～Ⅳ期者（分别为18％、18％），两者分别比较，差异均有统计学意义（P值分别为0．018、0．004）。当联合分析TM4SF1、C1D、TIZ、FXR1基因的重组抗原的相应IgG型自身抗体及TIZ、FXR1基因的重组抗原的相应IgM型自身抗体（即自身抗体谱）时，诊断卵巢癌的敏感度为66％，准确度为73％；将该自身抗体谱与CA125联合时，敏感度、准确度均有明显提高，分别为83％、80％。结论SEREX技术与SSH方法相结合筛选肿瘤抗原基因是一种行之有效的、能筛选出具有较高特异性肿瘤抗原基因的研究策略；TM4SF1、C1D、TIZ、BARD1、FXR1、OV-189基因的重组抗原在血清中的相应自身抗体可作为卵巢癌诊断的标志物，多个抗原的联合检测可提高诊断效率。     

人附睾蛋白4检测早期卵巢癌

卵巢癌是威胁女性生命健康的三大生殖道恶性肿瘤之一,其年轻化趋势明显且死亡率高居首位,如何提高卵巢癌患者早期检出率是降低该病死亡率的关键。传统卵巢癌标记物——糖类抗原125(CA125)虽然广泛应用于临床,但是敏感度和特异度较低,并且在一些妇科良性疾病中也出现非特异性的升高,因此迫切需要一种高敏感度和特异度的检测指标。近年来颇受瞩目的血清标记物——人附睾蛋白4(HE4)成为了早期诊断卵巢癌的焦点,相比于CA125,HE4在大多数非卵巢恶性肿瘤中不表达或低表达,并且单独检测HE4或联合CA125在对卵巢癌的早期诊断、疗效和预后评价等方面更具优势,现已在国外和国内多家三甲医院推广应用。现对HE4的发现、发展和临床应用及其与CA125构建的卵巢恶性肿瘤发病风险模型(ROMA)作综述。     

血清可溶性间皮素相关肽在卵巢良恶性肿瘤鉴别诊断中的应用

目的探讨血清可溶性间皮素相关肽(SMRP)在卵巢良恶性肿瘤鉴别诊断中的临床意义。方法血清标本取自2008年1月至2010年7月白求恩国际和平医院100例卵巢肿物患者及40例健康志愿者,ELISA试剂盒测定血清SMRP,化学发光法测定血清CA125,比较血清SMRP和CA125在卵巢良恶性肿瘤中的分布,绘制SMRP的ROC曲线,确定最佳截断值,评价诊断效能。结果卵巢癌组血清SMRP高于良性肿瘤组和健康对照组(P=0.000),良性肿瘤组与健康对照组相比差异无统计学意义(P=0.072)。SMRP的最佳截断值为1.103nmol/L,敏感度(77.27%)稍低,但特异度(97.92%)明显高于CA125。与临床诊断一致性方面,SMRP略优于CA125。结论血清SMRP可能是卵巢良恶性肿瘤鉴别诊断的良好指标。     

Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer

OBJECTIVES: In an ongoing effort to identify diagnostic ovarian cancer biomarkers, SEREX (serological analysis of recombinant cDNA expression libraries) technique was employed resulting in detection of 20 known genes, nine ESTs and one novel sequence. Interleukin-8 (IL-8) was one of ovarian cancer-associated antigens identified by SEREX screening. The objective of this study was, therefore, to evaluate the potential importance of circulating anti-IL-8 antibody as ovarian cancer biomarker. METHODS: We developed and optimized a new immunofluorescent bead-based assay for detection of anti-IL-8 antibody in blood serum. Circulating IL-8 and anti-IL-8 IgG concentrations were measured in blood sera from 44 patients with early stage (I-II) ovarian cancer, 50 patients with late stage (III-IV) ovarian cancer, 37 patients with benign pelvic masses, and 80 healthy women using the bead-based assay. RESULTS: Our data indicate that serum contains IL-8 cytokine, anti-IL-8 antibody, and IL-8:anti-IL-8 complexes. We found that concentrations of IL-8 and anti-IL-8 antibody were elevated in sera of patients with ovarian cancer as compared with healthy controls. Logistic regression analysis of circulating concentrations of anti-IL-8 IgG in patients with stages I-II ovarian cancer versus healthy controls allowed for prediction of early ovarian cancer with 98% specificity, 65.5% sensitivity, 80.3% of patients correctly classified. Combining IL-8 and anti-IL-8 IgG with CA 125 resulted in increased classification power as compared to individual markers analyzed separately. CONCLUSION: Thus, IL-8 and anti-IL-8 autoantibody might potentially serve as additional biomarkers for ovarian cancer.     

4种肿瘤标志物对上皮性卵巢癌定性诊断价值的初步研究

目的：探讨多胺（ＰＡ）、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９在定性诊断上皮性卵巢癌中的价值。方法：应用ＨＰ％Ｍ高效液相色谱仪和ＨＰ１０４０Ａ荧光检测器或酶联免疫吸附法测定上皮性卵巢癌４０例和卵巢良性肿瘤１８例血清中ＰＡ、ＣＡ１２５、ＣＡ１５．３和ＣＡ１９．９水平。结果：４种标志物中，ＰＡ诊断卵巢癌的敏感性、阳性预测率、阴性预测率和预测准确率最高，其次是ＣＡ１２５。结论：ＰＡ对人类恶性肿瘤缺乏特异性，但可作为鉴别卵巢良、恶性病变的有价值标志物。联合测定ＰＡ和ＣＡ１２５时，其敏感率为９４．９％。因此，联合测定ＰＡ和ＣＡ１２５可作为筛查卵巢良、恶性肿瘤的方法。     

志贺毒素2A-促黄体生成素释放激素重组毒素的构建、表达及其意义

目的 构建一种对子宫颈癌HeLa细胞有特异性杀伤作用的志贺毒素2A-促黄体生成素释放激素(Stx2A-LHRH)重组毒素,以探索其成为新型靶向药物的可能性。方法 用聚合酶链反应(PCR)技术扩增Stx2A-LHRH DNA片段,克隆至pET-20b( )质粒中,酶切鉴定及测序证明成功地构建了重组毒素表达质粒pET-Stx2A-LHRH,将其转染大肠杆菌BL21(DE3)菌株后,以异丙基-β-D硫代半乳糖苷诱导,十二烷基磺酸钠-聚丙烯酰胺凝胶(SDS-PAGE)电泳及凝胶薄层扫描分析Stx2A-LHRH重组毒素的表达情况。倒置显微镜下观察Stx2A-LHRH对HeLa细胞的作用。结果 SDS-PAGE电泳分析显示,在实验上清液中,诱导出相对分子质量为38000的融合蛋白,说明该载体表达了Stx2A-LHRH重组毒素,且其表达量占上清液中总蛋白的10．32％。加入Stx2A-LHRH重组毒素后,宫颈癌HeLa细胞几乎全部死亡。结论 成功构建了Stx2A-LHRH重组毒素,为研制治疗子宫颈癌的新型药物提供了理论依据。     

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.     

国产人附睾分泌蛋白4（HE4）ELISA试剂盒与CA_（125）联合诊断上皮性卵巢癌的研究

目的评价人附睾分泌蛋白4（HE4）ELISA试剂盒与CA125联合诊断卵巢癌的意义;方法两种（HE4）ELISA法检测上皮性卵巢癌114例。对照组为盆腔包块疑似样本59例,其他妇科良性疾病30例,肺癌、结直肠癌及乳腺癌患者45例,孕妇血清30例,正常人血清100例。实验组检测CA125。结果 HE4_义翘和HE4_康乃格试剂盒诊断卵巢癌敏感性为74.6%和70.2%,联合CA125诊断敏感性为73.2%和68.8%;在早期和晚期卵巢癌的诊断中,HE4_义翘试剂盒敏感性为66.7%和79%,HE4_康乃格试剂盒敏感性为48.1%和79%;HE4_义翘联合CA125敏感性为66.7%和77.2%,HE4_康乃格联合CA125敏感性为48%和77.2%。两试剂盒在各组数据中有强的相关性,相关系数为0.963。结论 HE4_义翘试剂盒在早期诊断卵巢癌方面较好。     

Preoperative plasma osteopontin level as a biomarker complementary to carbohydrate antigen 125 in predicting ovarian cancer

AIM: New biomarkers other than carbohydrate antigen (CA) 125 are needed for the detection of ovarian cancer. Osteopontin (OPN) is one of the candidates identified by high-throughput complementary DNA microarray techniques. We evaluated the preoperative plasma OPN level as a diagnostic biomarker for ovarian cancer in comparison with CA125. METHODS: Preoperative plasma OPN and CA125 levels were measured and compared in 32 patients with ovarian cancer, 34 patients with benign ovarian tumor, 30 patients with other gynecologic cancers and 31 healthy women. Preoperative plasma OPN levels were also assessed according to tumor stage, the volume of ascites and histological types. The sensitivity and specificity for predicting ovarian cancer was compared between OPN and CA125. RESULTS: Preoperative plasma OPN levels were significantly higher in patients with ovarian cancer than in those with benign ovarian tumor, in other gynecologic patients or in healthy women. Stage IV ovarian cancer patients and ovarian cancer patients with ascites had higher plasma OPN levels than those without ascites and in a lower stage. There was no relation between OPN and the histological type. The sensitivity of preoperative plasma OPN in detecting ovarian cancer was 81.3% and almost reached that of CA125. The specificity was moderate. Sensitivity increased to 93.8% with the combination of CA125, compared to 84.4% with CA125 alone. CONCLUSION: Preoperative OPN is a useful biomarker for predicting ovarian cancer. It is especially useful when used complementary to CA125. Larger studies of patients with ovarian cancer showing a low CA125 level or in early stages of ovarian cancer are needed.     

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.