Clinical epigenetics · 2021
Diagnosis of pulmonary nodules by DNA methylation analysis in bronchoalveolar lavage fluids.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Li Lei, Ye Zhujia, Yang Sai, Yang Hao, Jin Jing, Zhu Yingying, Tao Jinsheng, Chen Siyu, Xu Jiehan, Liu Yanying, Liang Weihe, Wang Bo, Yang Mengzhu, Huang Qiaoyun, Chen Zhiwei, Li Weimin, Fan Jian-Bing, Liu Dan
Аннотация
BACKGROUND: Lung cancer is the leading cause of cancer-related mortality. The alteration of DNA methylation plays a major role in the development of lung cancer. Methylation biomarkers become a possible method for lung cancer diagnosis.
RESULTS: We identified eleven lung cancer-specific methylation markers (CDO1, GSHR, HOXA11, HOXB4-1, HOXB4-2, HOXB4-3, HOXB4-4, LHX9, MIR196A1, PTGER4-1, and PTGER4-2), which could differentiate benign and malignant pulmonary nodules. The methylation levels of these markers are significantly higher in malignant tissues. In bronchoalveolar lavage fluid (BALF) samples, the methylation signals maintain the same differential trend as in tissues. An optimal 5-marker model for pulmonary nodule diagnosis (malignant vs. benign) was developed from all possible combinations of the eleven markers. In the test set (57 tissue and 71 BALF samples), the area under curve (AUC) value achieves 0.93, and the overall sensitivity is 82% at the specificity of 91%. In an independent validation set (111 BALF samples), the AUC is 0.82 with a specificity of 82% and a sensitivity of 70%.
CONCLUSIONS: This model can differentiate pulmonary adenocarcinoma and squamous carcinoma from benign diseases, especially for infection, inflammation, and tuberculosis. The model's performance is not affected by gender, age, smoking history, or the solid components of nodules.
RESULTS: We identified eleven lung cancer-specific methylation markers (CDO1, GSHR, HOXA11, HOXB4-1, HOXB4-2, HOXB4-3, HOXB4-4, LHX9, MIR196A1, PTGER4-1, and PTGER4-2), which could differentiate benign and malignant pulmonary nodules. The methylation levels of these markers are significantly higher in malignant tissues. In bronchoalveolar lavage fluid (BALF) samples, the methylation signals maintain the same differential trend as in tissues. An optimal 5-marker model for pulmonary nodule diagnosis (malignant vs. benign) was developed from all possible combinations of the eleven markers. In the test set (57 tissue and 71 BALF samples), the area under curve (AUC) value achieves 0.93, and the overall sensitivity is 82% at the specificity of 91%. In an independent validation set (111 BALF samples), the AUC is 0.82 with a specificity of 82% and a sensitivity of 70%.
CONCLUSIONS: This model can differentiate pulmonary adenocarcinoma and squamous carcinoma from benign diseases, especially for infection, inflammation, and tuberculosis. The model's performance is not affected by gender, age, smoking history, or the solid components of nodules.