Abstract: Objective　To evaluate the diagnostic value of RASSF1A and SHOX2 gene methylation detection combined with rapid on-site cytological evaluation (C-ROSE) in lung cancer. Methods　A total of 179 patients suspected lung cancer patients with RASSF1A and SHOX2 methylation detection and definite pathological diagnosis were selected, including 58 cases of lung cancer and 121 cases of benign lung disease. C-rose detection was performed in 114 of 179 patients (45 lung cancers and 69 benign lung lesions) by Diff-quick staining. Using pathological results as the gold standard, the sensitivity and specificity of RASSF1A, SHOX2 methylation and/or C-ROSE in the diagnosis of lung cancer were analyzed. The consistency between the results of RASSF1A and SHOX2 methylation in different specimen types and different tumor types and pathological diagnosis was determined. Results　The sensitivity and specificity of RASSF1A combined with SHOX2 methylation detection were 77.59% (45/58) and 80.17% (97/121), respectively. In the subgroup analysis, the coincidence rates between methylation and pathological diagnosis in lung biopsy and biopsy and alveolar lavage fluid (BALF) specimens were 88.89% (8/9) and 79.75% (126/158), respectively, while the consistency of pleural fluid was less than 63.64% (7/11). In the subgroup analysis of lung cancer types, the accuracy of methylation detection was 100% (5/5) and 92.31% (12/13) in lung small cell carcinoma and squamous cell carcinoma. which was 66.67% (18/27) in lung adenocarcinoma. The sensitivity and specificity of C-ROSE detection were 75.56% (34/45) and 95.65% (66/69) respectively. The sensitivity of methylation detection combined with C-ROSE was 86.96% (39/45), and the specificity was 86.67% (60/69). Conclusion　RASSF1A, SHOX2 gene methylation and C-ROSE have a good sensitivity and specificity for the diagnosis of lung cancer. The combination of the two will become an effective supplementary means for pathological diagnosis, and help to further improve the diagnostic efficiency of lung cancer.

Key words: lung neoplasms, DNA methylation, diagnosis, ras association domain family 1A, short stature homeobox 2, cytological rapid on-site evalutation