Diagnostic value of exfoliated tumor cells combined with DNA methylation in bronchoalveolar lavage fluid for lung cancer

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BACKGROUND: To evaluate the diagnostic value of exfoliated tumor cells (ETCs) numbers combined with DNA methylation levels in bronchoalveolar lavage fluid (BALF) in lung cancer. METHODS: BALF samples were collected from 43 patients with lung cancer and 23 with benign lung disease. ETCs were detected by the nano-enrichment method, and the methylation status of the short stature homeobox gene 2 (SHOX2) and the RAS association domain family 1, isoform A (RASSF1A) gene were detected by RT-PCR. The diagnostic value of each metric was evaluated by receiver operating characteristic curve analysis, specificity and sensitivity. RESULTS: The sensitivity/specificity of RASSF1A and SHOX2 methylation detection were 44.12%/76.47% and 93.75%/87.50%, respectively. When "RASSF1A/SHOX2 methylation" was used as a positive result, the sensitivity increased to 88.24%, and the specificity decreased to 81.25%. When "RASSF1A + SHOX methylation" was used as positive, the sensitivity was reduced to 32.35%, but the specificity was increased to 100.00%. The sensitivity and specificity of ETCs detection in BALF were 89.47% and 16.67%, respectively. When "SHOX2/RASSF1A methylation + ETCs was used as a positive result, the sensitivity and specificity of the detection were 79.31% and 81.82%, respectively. When "SHOX2 + RASSF1A + ETCs" was used as positive, the sensitivity was 34.48% and the specificity was 90.91%. Receiver operating characteristic curve analysis showed that when SHOX2, RASSF1A methylation and ETCs were combined, the diagnostic sensitivity increased to 0.778. CONCLUSION: ETCs counting in combination with SHOX2 and RASSF1A methylation assays in BALF samples has demonstrated excellent sensitivity for lung cancer diagnosis and is an effective complementary tool for clinical diagnosis of lung cancer.

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