Benign lung diseases are common and often do not require specific treatment, but they pose challenges in the distinguishing of them from lung cancer during low-dose computed tomography (LDCT). This study presents a comprehensive methylation analysis using real-time PCR for minimally invasive diagnoses of lung cancer via employing BALF exosome DNA. A panel of seven epigenetic biomarkers was identified, exhibiting specific methylation patterns in lung cancer BALF exosome DNA. This panel achieved an area under the curve (AUC) of 0.97, with sensitivity and specificity rates of 88.24% and 97.14%, respectively. Each biomarker showed significantly higher mean methylation levels (MMLs) in both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to non-cancer groups, with fold changes from 1.7 to 13.36. The MMLs of the biomarkers were found to be moderately elevated with increasing patient age and smoking history, regardless of sex. A strong correlation was found between the MMLs and NSCLC stage progression, with detection sensitivities of 79% for early stages and 92% for advanced stages. In the validation cohort, the model demonstrated an AUC of 0.95, with 94% sensitivity and specificity. Sensitivity for early-stage NSCLC detection improved from 88.00% to 92.00% when smoking history was included as an additional risk factor.
良性肺疾病较为常见且通常无需特殊治疗，但在低剂量计算机断层扫描（LDCT）中与肺癌的鉴别诊断存在挑战。本研究通过采用支气管肺泡灌洗液（BALF）外泌体DNA进行实时荧光定量PCR，开展了全面的甲基化分析以实现肺癌微创诊断。研究鉴定出包含七个表观遗传生物标志物的组合，该组合在肺癌BALF外泌体DNA中呈现特异性甲基化模式。该标志物组合的曲线下面积（AUC）达0.97，敏感性与特异性分别为88.24%和97.14%。与非癌组相比，各生物标志物在非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）中的平均甲基化水平（MML）均显著升高，倍数变化范围为1.7至13.36。研究发现无论性别如何，生物标志物的MML均随患者年龄增长和吸烟史延长呈适度升高趋势。MML与NSCLC分期进展呈强相关性，早期和晚期检测敏感性分别为79%和92%。在验证队列中，该模型AUC为0.95，敏感性与特异性均达94%。当纳入吸烟史作为附加风险因素时，早期NSCLC检测敏感性从88.00%提升至92.00%。
Discrimination of Lung Cancer and Benign Lung Diseases Using BALF Exosome DNA Methylation Profile
肿瘤(癌症)患者之家