Diagnostic Efficacy Of SHOX2 And RASSFLA DNA Methylation For Lung Cancer In Bronchoalveolar Lavage Fluid

ObjectiveAim to evaluate the diagnostic efficacy of short stature homeobox 2(SHOX2)and Ras association domain family 1A(RASSF1A)genes methylation for lung cancer in bronchoalveolar lavage fluid(BALF).Synchronous collection of serum CEA and cytological examination result for cancer cells in BALF,comparative and analysis of the diagnostic efficacy.MethodsA total of 60 patients were included from a AAA hospital in this study.The methylation status of SHOX2 and RASSF1 A genes in BALF was detected by methylation specific real-time quantitative polymerase chain reaction(q MSP).Collected EGFR,ROS1,ALK,BRAF gene mutation detection result to analyze the correlation with SHOX2 and RASSF1 A gene methylation use Fisher exact test.Serum CEA and cytology were collected simultaneously.Analyze the sensitivity and specificity of SHOX2 and RASSF1 A gene methylation,cytological examination and serum CEA in the diagnosis of lung cancer.The area under the receiver operating characteristic(ROC)curves was used to estimate the diagnostic efficacy.Results1.In BALF,the sensitivity and specificity of SHOX2 and RASSF1 A gene methylation in diagnosis of lung cancer were 45.5% and 100.0%,respectively.The SHOX2 and RASSF1 A gene methylation panel in BALF had the highest AUC value of 0.727(95%CI: 0.598～0.856),comparing with cytological examination(AUC value: 0.716,95%CI: 0.584～0.847)and serum CEA(AUC value: 0.565,95%CI:0.398～0.732).SHOX2 and RASSF1 A gene methylation combined with cytology and serum CEA can further improve the diagnostic efficiency of lung cancer(AUC value:0.813,95%CI: 0.706～0.921).2.Lesion size,transverse distribution,lesion characteristic,pleural thickening,bronchial cut-off sign,pleural indentation sign and pulmonary emphysema were related with the positive detection rate of methylation in BALF(P<0.05).3.Analyzed gene test results of 31 patients with non-small cell lung cancer(NSCLC),the mutation rate of EGFR gene was 80.6%(25/31).There was no significant correlation between the methylation results of SHOX2 and RASSF1 A genes and EGFR gene mutations(P>0.05).Conclusion1.The positive rate and the diagnostic specificity of SHOX2 and RASSF1 A gene methylation in lung cancer patients is significantly higher than that in benign lung disease.The SHOX2 and RASSF1 A gene methylation have a great auxiliary effect on distinguish between benign and malignant lung lesions.2.The SHOX2 and RASSF1 A methylation panel in BALF showed good diagnostic efficacy in lung cancer diagnosis.Methylation is a promising biomarker to early diagnosis of lung cancer for the non-invasive diagnosis.3.In 1～3 cm and 3～5 cm groups,the sensitivity of SHOX2 and RASSF1 A gene methylation detection was better than that of serum CEA and Cytology.Methylation of SHOX2 and RASSF1 A genes can assist imaging diagnosis in patients with suspected lung cancer.4.There was no significant correlation between SHOX2 and RASSF1 A gene methylation test results and EGFR gene mutation in NSCLC.