Qiao Rong, Zhou Xiajie, Li Wenli, Zhong Runbo, Wang Jun, Song Yakang, Zhang Jing, Xu Tian, Wang Yue, Dai Liping, Gu Wanjian, Han Baohui, Yang Rongxi
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
Lung Cancer Manag. 2025 Dec;14(1):2477411. doi: 10.1080/17581966.2025.2477411. Epub 2025 Apr 1.
Blood-based DNA methylation biomarkers have great potential for the early detection of lung cancer (LC). Here, we investigated the association between methylation in peripheral blood and LC.
Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was performed to measure the methylation levels of 4 CpG sites in gene in two independent case-control studies (168 LC cases and 167 controls in Study I, 677 LC cases and 833 controls in Study II). Logistic regression adjusted for covariates was conducted for odds ratios (ORs) and 95% confidence intervals (CIs). Non-parametric tests were applied for the comparisons of stratified groups.
Hypomethylation of all 4 CpG sites in was associated with early-stage LC in the two studies (ORs range from 1.91 to 3.07 in Study I, ORs range from 1.39 to 1.86 in Study II, < 0.05 for all). The associations were still significant for the very early-stage LC patients (stage I). Subgroup analysis indicated that the associations could be enhanced by male gender and older age. Moreover, decreased methylation was correlated with increased tumor size, tumor length and stage.
Our results suggested blood-based hypomethylation as a potential biomarker for LC early detection.
基于血液的DNA甲基化生物标志物在肺癌（LC）早期检测中具有巨大潜力。在此，我们研究了外周血甲基化与肺癌之间的关联。
在两项独立的病例对照研究中（研究I有168例肺癌病例和167例对照，研究II有677例肺癌病例和833例对照），采用基质辅助激光解吸电离飞行时间（MALDI-TOF）质谱法测量基因中4个CpG位点的甲基化水平。对协变量进行逻辑回归分析以计算优势比（OR）和95%置信区间（CI）。应用非参数检验对分层组进行比较。
在两项研究中，该基因所有4个CpG位点的低甲基化均与早期肺癌相关（研究I中OR范围为1.91至3.07，研究II中OR范围为1.39至1.86，所有P均<0.05）。对于极早期肺癌患者（I期），这种关联仍然显著。亚组分析表明，男性和老年可增强这种关联。此外，该基因甲基化降低与肿瘤大小、肿瘤长度增加及分期相关。
我们的结果表明基于血液的该基因低甲基化是肺癌早期检测的潜在生物标志物。
