血清分泌型丝氨酸蛋白酶抑制剂Kazal 1型对浸润性肺腺癌的诊断价值

Diagnostic value of serum serine protease inhibitor Kazal type 1 in invasive lung adenocarcinoma

目的探讨血清分泌型丝氨酸蛋白酶抑制剂Kazal 1型(SPINK1)对浸润性肺腺癌的诊断价值。方法收集2014年1月至2019年12月在浙江大学舟山医院就诊的153例肺腺癌患者和28例健康志愿者,采用ELISA法分别检测两组受试者血清SPINK1浓度,荧光定量PCR法和免疫组织化学染色法检测肺腺癌患者的癌组织与癌旁组织SPINK1 mRNA表达水平和蛋白表达情况。分析肺腺癌患者血清与癌组织SPINK1表达水平的相关性、血清SPINK1与肺腺癌患者临床病理特征的关系。结果浸润性肺腺癌患者血清SPINK1浓度明显高于健康志愿者和浸润性腺癌患者,差异均有统计学意义(均P<0.05)。血清SPINK1浓度与癌组织SPINK1 mRNA表达水平呈正相关(r=0.277,P=0.014)。血清SPINK1低浓度患者主要分布于SPINK1蛋白低表达组,而血清SPINK1高浓度患者主要分布于SPINK1蛋白高表达组,差异均有统计学意义(均P<0.05)。血清SPINK1低浓度与高浓度患者在性别、年龄、吸烟史、淋巴结转和胸膜侵犯间比较差异均无统计学意义(均P>0.05),而在病理类型、肿瘤大小以及TNM分期间比较差异均有统计学意义(均P<0.05)。单因素及多因素分析显示,血清SPINK1浓度(OR=1.967,95%CI:1.116~4.116,P=0.033)、癌胚抗原(CEA)(OR=2.189,95%CI:1.211~5.516,P=0.025)和肿瘤大小(OR=2.121,95%CI:1.200~5.226,P=0.034)是浸润性肺腺癌独立预测因素。血清SPINK1浓度绘制ROC曲线,AUC为0.83,最佳截断值为1288.5729 pg/ml,灵敏度为0.743,特异度为0.827。结论肺腺癌患者血清SPINK1浓度升高可以反映癌组织SPINK1表达水平,对浸润性肺腺癌具有潜在的诊断价值。

Objective To investigate the application of serumserine protease inhibitor Kazal type 1(SPINK1)for diagnosis of invasive lung adenocarcinoma.Methods One hundred and fifty three patients with lung adenocarcinoma treated in Zhoushan Hospital of Zhejiang Province from January 2014 to December 2019 were recruited.Serum levels of SPINK1 were detected by ELISA in lung cancer patients and 28 healthy controls;the expression of SPINK1 mRNA and protein in lung adenocarcinoma tissues and paracancer tissues of lung cancer patients were detected by fluorescence quantitative PCR and immunohistochemistry.The correlation between the serum level and tissue expression of SPINK1 in lung adenocarcinoma was analyzed.The relationship between serum SPINK1 and the clinicopathological characteristics of lung adenocarcinoma was also analyzed.Results The level of serum SPINK1 in patients with lung adenocarcinoma was significantly higher than that of the control group(both P<0.05).The serum level of SPINK1 was positively correlated with the expression level of SPINK1 mRNA in cancer tissues(r=0.277,P=0.014).The level of serum SPINK1 was not correlated with sex,age,smoking history,lymph node metastasis and pleural invasion,but significantly correlated with pathological type,tumor size and TNM stage(all P<0.05).Multivariate analysis showed that the serum SPINK1 level,CEA level and tumor size were the independent predictors of invasive pulmonary adenocarcinoma(OR=1.967,95%CI:1.116-4.116,P=0.033,OR=2.189,95%CI:1.211-5.516,P=0.025,OR=2.121,95%CI:1.200-5.226,P=0.034,respectively).The area under the ROC curve(AUC)of SPINK1 for predict-ing invasive lung adenocarcinoma was 0.83,the optimum cut-off value was 1288.5729 pg/ml,the sensitivity was 0.743,and the specificity was 0.827.Conclusion The serum SPINK1 level in patients with lung adenocarcinoma can reflect the expression level of SPINK1 in cancer tissues,which has potential diagnostic value for lung adenocarcinoma.