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

摘要

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.%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.