血清人绒毛膜促性腺激素β亚单位与甲胎蛋白对纵隔生殖细胞源性肿瘤的诊断价值

Clinical diagnostic value of serum β-hCG and AFP in mediastinal germ cell tumor

目的探讨血清人绒毛膜促性腺激素B亚单位（β-HCG）、甲胎蛋白（AFP）在纵隔生殖细胞源性肿瘤中的诊断价值。方法回顾性分析2008年1月至2014年5月上海交通大学附属胸科医院的133例初诊并经病理确诊为各类纵隔肿瘤及肿瘤样病变患者的病历资料。根据第八版《外科学》进行纵隔肿瘤及肿瘤样病变的类型分组。病例研究组是42例纵隔生殖细胞源性肿瘤患者，对照组是91例其他纵隔肿瘤及肿瘤样病变患者（包括胸腺瘤31例、纵隔神经源性肿瘤10例、胸内甲状腺肿2例、纵隔囊肿25例、纵隔脂肪瘤2例、纵隔淋巴瘤11例及胸腺癌10例）。采用化学发光发检测AFP，采用电化学发光发检测β-HCG。对数据进行K-S正态性检验，呈非正态分布的资料以中位数（四分位数间距）表示。两组间计量资料的比较采用Mann-WhitneyU检验。多因素分析采用Logistic回归分析。采用ROC曲线分析诊断价值并确定临界值（cut-off）。结果病例组的血清AFP和B—HCG的检测水平分别为13．26（2．39～48．09）ng／ml和1．99（0．10-15．7）IU／L，显著高于对照组[AFP：2．47（1．78～3．16）ng／ml，β-HCG：0．10（0．10～0．55）IU／L]和对照组中的各疾病。病例组和对照组整体比较AFP和β-HCG的水平时，差异有统计学意义（P均为0．000）。分别比较时，除β-HCG在病例组和胸内甲状腺肿间无显著差异外，病例组的两指标水平与对照组各疾病相比，差异均有统计学意义。单独检测AFP和B．HCG从纵隔肿瘤及肿瘤样病变中鉴别诊断出纵隔生殖细胞源性肿瘤的cut-off值分别为5．07ng/ml和2．32IU／L；敏感度分别为57．1％和50．0％，特异度分别为97．8％和96．7％，准确性分别为54．9％和46．7％，曲线下面积（AUC）分别为0．773和0．755，阳性似然比分别为26．00和15．17。AFP与β-HCG并联将鉴别诊断出纵隔生殖细胞源性肿瘤的敏感度提高到71．4％；由Logistic回归模型进一步获得预测概率P=1／[1＋exp（-0．319AFP-0．253HCG＋2．850）]，在其cut．off值取0．30时，特异度、AUC、阳性似然比分别提高到98．9％、0．835及65．00，阴性似然比降低到0．29，阳性预测值（96．8％）和阴性预测值（88．2％）也有所提高。结论血清β-HCG、AFP联合诊断的预测概率P对纵隔生殖细胞源性肿瘤的诊断可能有一定的临床价值。

Objective To explore the clinical diagnostic value of serum human chorionic gonadotropin beta subunit （β-HCG） and alpha fetoprotein （AFP） in mediastinal germ cell tumors. Methods A retrospective analysis was conducted on the patients who were definitely diagnosed as mediastinal tumors or mediastinal neoplastic lesions. A total of 133 patients were included for analysis between January 2008 and May 2014, divided into two groups. 42 cases of mediastinal germ cell tumor patients were marked as case group while 91 cases of other mediastinal tumor or mediastinal neoplastic lesion patients were marked as control group （including 31 cases of thymoma, 10 cases of mediastinal neurogenic tumor, 2 cases ofintrathoracic goiter, 25 cases of mediastinal cyst, 2 cases of mediastinal lipoma, 11 cases of mediastinal lymphoma and 10 cases of thymic carcinoma）. AFP was detected by chemiluminescence detection, and - HCG was detected by electrochemical luminescence. K-S test was performed to investigate normality of data, non-normally distributed data were described as Median （ interquartile range）. Mann-Whitney U test was done for measurement of data between two groups. Logistic regression analysis was performed as multivariate analysis. Receiver operating characteristic curve （ROC） was used to determine the cut-off values. Results The levels of serum AFP and β-HCG in case group were 13.26 （2. 39 -48.09） ng/ml and 1.99 （0. 10 - 15.7） IU/L, respectively, significantly higher than those in control group[ AFP：2.47 （1.78 -3.16） ng/ ml, 15-HCG： 0. 10 （0. 10 -0. 55） IU/L]. The difference of levels of AFP and ~β-ICG between the case group and the control group were statistically significant （ P = 0. 000）. There were no significant difference when it comes to β-HCG between the case group and intrathoracic goiter patients in control group. Apart from it, the difference of levels of AFP and β-HCG between the case group and every single control group were statistically significant. Cut-off values of AFP and β-HCG for distinguishing mediastinal germ cell tumors from mediastinal tumors were 5.07 ng/ml and 2. 32 IU/L. In this scenario, for AFP and f3-HCG, sensitivity were 57. 1% and 50%, specificity were 97.8% and 96. 7%, accuracy were 54. 9% and 46. 7%, area under the curve （AUC） were 0. 773 and 0. 755, positive likelihood ratios were 26. 00 and 15.17respectively. Parallel experiments contributed to increase the sensitivity to 71.4%. Predictive probability （P） = 1/[ 1 ＋ exp （ -0. 319AFP -0. 253HCG ＋ 2. 850） ] was obtained by logistic regression model. When cut-off value of predictive probability （P） was 0. 30, specificity, AUC, and positive likelihood ratio were increased to 98.9%, 0. 835 and 65.00respectively, negative likelihood ratio was decreased to 0. 29, positive predictive value and negative predictive value were increased also （96. 8% and 88.2% respectively）. Conclusion Serum β-HCG, AFP and predictive probability （ P ） is valuable in the diagnosis of mediastinal germ cell tumor.