关键词: 肺肿瘤, 肺疾病, 甲基化, SHOX2基因, 血清肿瘤标志物, 诊断, 灵敏度, 特异度

Abstract: Objective　To evaluate the value of SHOX2 gene methylation level for differential diagnosis in patients with lung cancer and benign lung diseases.Methods　Patients with lung cancer and benign lung diseases hospitalized in the Department of Thoracic Surgery and Department of Eespiration of the Central Hospital of Wuhan from March 2014 to June 2016 were enrolled.Among them，173 patients with lung cancer were defined as lung cancer group，and 194 patients with benign lung diseases as benign lung disease group.Routine serological examination and tumor markers were detected in all patients.The SHOX2 gene methylation was detected by Sanger sequencing，and the SHOX2 gene methylation level was calculated by △△CT method.The value of each index in differential diagnosis of lung cancer was analyzed by receiver operating characteristic（ROC） curve.The relationship between each index and lung cancer pathological type and TNM staging was analyzed.Results　The white blood cell count（WBC） and △△CT value of lung cancer group were lower than those of benign lung disease group，while the serum gastrin releasing peptide precursor（ProGRP），squamous cell carcinoma antigen（SCC-Ag），cytokeratin 21 fragment antigen（Cyfra21-1） and carcinoembryonic antigen（CEA） were higher than those in benign lung disease group（P<0.05）. The result of multivariate Logistic regression analysis showed that serum ProGRP，serum Cyfra21-1，and △△CT values were factors influencing lung cancer（P<0.05）. The area under ROC curve（AUC） of △△CT value for the diagnosis of lung cancer was 0.843.The sensitivity was 58.2%，and the specificity was 93.1% when the optimal threshold was 2.69.The AUC of serum ProGRP was 0.711，with optimal threshold of 32 ng/L，sensitivity of 63.5% and specificity of 77.4%.The AUC of serum Cyfra21-1 was 0.677，the best cut-off value 2.92 μg/L，sensitivity 56.1%，and specificity 72.3%.The AUC of serum ProGRP for the diagnosis of lung cancer was greater than that of serum Cyfra21-1（Z=3.569，P=0.038）. The AUC of the △△CT value combined with serum ProGRP was 0.860.The AUC of △△CT value combined with serum ProGRP in the diagnosis of lung cancer were greater than that of △△CT value，serum ProGRP，and serum Cyfra21-1（Z=4.046，Z=5.607，Z=8.215，P<0.05）. The △△CT value of patients with squamous cell carcinoma，small cell carcinoma was lower than that of patients with adenocarcinoma，large cell carcinoma and other unknown pathological types（P<0.05）. The △△CT value of patients in stage Ⅲ lung cancer was lower than that of those in stage Ⅰ and stage Ⅱ（P<0.05），and the △△CT value of patients in stage Ⅳ lung cancer was lower than that of those in stage Ⅰ，stage Ⅱ and stage Ⅲ（P<0.05）. Conclusion　SHOX2 gene methylation has its value in the differentiation of lung cancer and benign lung disease.It is correlated with lung cancer pathological type and TNM staging，which can be used as an auxiliary index for diagnosis of lung cancer.

Key words: Lung neoplasms, Lung diseases, Methylation, SHOX2 gene, Serum tumor marker, Diagnosis, Sensitivity, Specificity