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目的探讨甲状腺转录因子(TTF-1)、天冬氨酸蛋白酶A(NapsinA)、转录因子P63(P63)和细胞角蛋白5/6(CK5/6)在肺癌组织中的表达,以及在肺癌组织学分型中的诊断价值。方法采用免疫组化染色检测964例肺癌患者癌组织TTF-1(929例)、NapsinA(113例)、P63(282例)、CK5/6(277例)蛋白的表达,分析蛋白表达与肺癌临床病理特征的关系;采用受试者工作特征(ROC)曲线分析4个因子各自的诊断价值,计算其曲线下面积(AUC),分析其表达阳性时分型诊断的敏感性和特异性。对同时检测了4个因子表达的44例患者行多因素logistic回归分析,检验其判定肺鳞癌/肺腺癌的价值。结果本研究纳入964例肺癌患者,其中腺癌552例,鳞癌146例,小细胞肺癌253例,大细胞肺癌13例;平均年龄56岁,男性占63.4%。TTF-1、NapsinA、P63和CK5/6在肺癌组织中的阳性表达率分别为76.3%(709/929)、67.3%(76/113)、47.2%(133/282)和34.7%(96/277)。TTF-1、NapsinA在腺癌中的阳性表达率高,其表达阳性时诊断肺腺癌的敏感性分别为81.15%、82.05%,特异性分别为30.41%、65.71%,AUC分别为0.557 8(P=0.002 6,95%CI:0.520 0~0.595 6)、0.738 8(P<0.000 1,95%CI:0.633 4~0.844 2)。P63、CK5/6在鳞癌中的阳性表达率高,其表达阳性时诊断肺鳞癌的敏感性分别为80.68%、81.25%,特异性分别为68.04%、84.26%,AUC为0.7436(P<0.000 1,95%CI:0.681 9~0.805 3)、0.827 6(P<0.000 1,95%CI:0.770 0~0.885 2)。小样本(44例肺鳞癌/肺腺癌)多因素回归分析发现,NapsinA阳性可独立诊断肺腺癌(偏回归系数=2.826,P=0.022),而其他指标不具有独立进行肺鳞癌/肺腺癌分型诊断的价值(P>0.05)。结论 TTF-1和NapsinA均可作为诊断肺腺癌的生物标志物,P63、CK5/6可作为诊断肺鳞癌的生物标志物。NapsinA阳性可于肺鳞癌/肺腺癌分型诊断中独立诊断肺腺癌。
Objective To investigate the expression of TTF-1, NapsinA, P63 and CK5 / 6 in lung cancer tissues, Diagnostic Value in Credit Type. Methods The expression of TTF-1 (929), NapsinA (113), P63 (282) and CK5 / 6 (277) in 964 lung cancer patients was detected by immunohistochemistry. (ROC) curves were used to analyze the diagnostic value of each of the four factors. The area under the curve (AUC) was calculated and the sensitivity and specificity of the diagnosis were analyzed. Multivariate logistic regression analysis was performed on 44 patients with simultaneous detection of four factors and their value in determining squamous cell carcinoma / lung adenocarcinoma was tested. Results A total of 964 patients with lung cancer were included in this study. Among them, 552 were adenocarcinoma, 146 were squamous cell carcinoma, 253 were small-cell lung cancer and 13 were large-cell lung cancer. The mean age was 56 years and the male was 63.4%. The positive rates of TTF-1, NapsinA, P63 and CK5 / 6 in lung cancer tissues were 76.3% (709/929), 67.3% (76/113), 47.2% (133/282) and 34.7% 277). The positive rates of TTF-1 and NapsinA in adenocarcinoma were 81.15% and 82.05%, respectively. The positive rates of TTF-1 and NapsinA in lung adenocarcinoma were 30.41% and 65.71%, respectively. The AUC were 0.557 8 P = 0.002 6,95% CI: 0.520 0-0.595 6), 0.738 8 (P <0.000 1,95% CI: 0.633 4-0.844 2). The positive rates of P63 and CK5 / 6 in squamous cell carcinoma were 80.68%, 81.25%, 68.04%, 84.26% respectively, and the AUC was 0.7436 (P < 0.000 1,95% CI: 0.681 9 ~ 0.805 3), 0.827 6 (P <0.000 1,95% CI: 0.770 0 ~ 0.885 2). Multivariate regression analysis showed that Napsin A positive diagnosis of lung adenocarcinoma independently (partial regression coefficient = 2.826, P = 0.022), while other indicators do not have an independent lung squamous cell carcinoma / The diagnostic value of lung adenocarcinoma (P> 0.05). Conclusion Both TTF-1 and NapsinA can be used as biomarkers for the diagnosis of lung adenocarcinoma. P63 and CK5 / 6 can be used as biomarkers for diagnosis of lung squamous cell carcinoma. NapsinA positive diagnosis of lung adenocarcinoma in lung squamous cell carcinoma / lung adenocarcinoma type diagnosis.