Zhu Qiang, Qiao Rong, Di Feifei, Song Yakang, Zhang Jin, Xu Tian, Wang Yue, Dai Liping, Gu Wanjian, Han Baohui, Yang Rongxi
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 210000, China.
Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
Clin Chim Acta. 2022 Dec 1;537:173-180. doi: 10.1016/j.cca.2022.10.014. Epub 2022 Nov 1.
Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Novel biomarkers for LC detection are urgently needed. Here we aimed to investigate the association between RPTOR methylation in peripheral blood and LC.
The methylation levels were measured by mass spectrometry in two independent case-control studies (159 LC cases vs. 188 controls in Study I, 413 LC cases vs. 687 controls in Study II). Logistic regression and Bonferroni correction were conducted to analyze the association.
RPTOR hypomethylation was discovered in Study I and validated in Study II. Combining the two studies, RPTOR_CpG_2 and RPTOR_CpG_8 showed significantly lower methylation levels in stage I cases (ORs per -10% methylation = 1.22 and 1.27, respectively, both P-values < 0.005). The significance kept between RPTOR_CpG_8 and LC cases with tumor length ≤ 1 cm (OR per -10% methylation = 1.39, P = 0.001). Moreover, methylation levels of all CpG sites were lower in cases at stage II & III than in those at stage I (all P-values less than 0.017).
Our study disclosed the association between RPTOR hypomethylation in peripheral blood and LC even in very early stage, suggesting the feasibility of blood-based DNA methylation for LC early detection.
肺癌是全球癌症相关死亡的主要原因。迫切需要用于肺癌检测的新型生物标志物。在此，我们旨在研究外周血中RPTOR甲基化与肺癌之间的关联。
在两项独立的病例对照研究中通过质谱法测量甲基化水平（研究I中159例肺癌病例与188例对照，研究II中413例肺癌病例与687例对照）。进行逻辑回归和Bonferroni校正以分析这种关联。
在研究I中发现RPTOR低甲基化，并在研究II中得到验证。合并两项研究，RPTOR_CpG_2和RPTOR_CpG_8在I期病例中显示出显著更低的甲基化水平（每-10%甲基化的优势比分别为1.22和1.27，P值均<0.005）。RPTOR_CpG_8与肿瘤长度≤1 cm的肺癌病例之间的显著性仍然存在（每-10%甲基化的优势比=1.39，P = 0.001）。此外，II期和III期病例中所有CpG位点的甲基化水平均低于I期病例（所有P值均小于0.017）。
我们的研究揭示了外周血中RPTOR低甲基化与肺癌之间的关联，甚至在非常早期阶段也是如此，这表明基于血液的DNA甲基化用于肺癌早期检测的可行性。
