Clinical Value of SHOX2 and RASSF1A Methylation Combination in BALF Samples for the Diagnosis of Lung Cancer

To evaluate the clinical utility of combined SHOX2 and RASSF1A methylation analysis in bronchoalveolar lavage fluid (BALF) for lung cancer diagnosis using methylation-specific PCR (MSP). The study aimed to combine BALF methylation results with bronchoscopic cytology, serum tumor markers, and imaging data to assess their diagnostic value. A total of 77 patients were recruited and divided into two groups: 57 patients with lung cancer and 20 control subjects. The methylation levels of SHOX2 and RASSF1A in BALF samples were analyzed using MSP. General data, serum markers, imaging, cytology, and pathology results were collected. The methylation levels were compared between the two groups, and differences in methylation levels across different pathological types and stages were analyzed. Receiver operating characteristic (ROC) curves were constructed to determine the cutoff values. The diagnostic performance of combined SHOX2 and RASSF1A methylation testing was compared with serum markers and cytology. The combined SHOX2 and RASSF1A methylation test showed a sensitivity of 68.42% and a specificity of 95%, significantly improving the detection rate of lung adenocarcinoma. Higher methylation levels were observed in advanced-stage lung cancer compared with early-stage cases. The combined SHOX2 and RASSF1A methylation test exhibited the highest sensitivity, with an area under the curve (AUC) of 0.817, compared with carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CY211), and BALF cytology. The combined use of BALF cytology and methylation testing increased the detection rate to 73.68%, higher than BALF cytology alone (40.35%). The odds ratio for positive SHOX2 and RASSF1A methylation in patients with bronchial cutoff signs was 15.167. Combined SHOX2 and RASSF1A methylation testing can serve as an auxiliary diagnostic tool for lung cancer, outperforming serum markers and BALF cytology in diagnostic efficacy. Additionally, it can complement BALF cytology and provide a more accurate diagnosis. The presence of bronchial cutoff signs can be used as a relevant factor to predict positive SHOX2 and RASSF1A methylation.