外周血甲基化水平与肺癌的发生发展相关
[Peripheral blood methylation level is associated with the occurrence and progression of lung cancer].
作者信息
Zang Z, Qiao R, Zhu Q, Zhou X, Gu W, Han B, Yang R
机构信息
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Mar 20;43(3):349-359. doi: 10.12122/j.issn.1673-4254.2023.03.03.
OBJECTIVE
To explore the association of gene methylation levels in peripheral blood with lung cancer.
METHODS
The methylation levels of 4 CpG sites in gene were quantitatively detected in 285 patients with lung cancer, 186 age- and sex-matched patients with benign pulmonary nodules and 278 matched healthy control subjects using mass spectrometry (MALDI-TOF-MS). The association of methylation levels with lung cancer was analyzed using logistic regression models adjusted for covariates. The methylation levels in different subgroups of lung cancer patients were compared using Mann-Whitney test.
RESULTS
In subjects over 55 years and in female subjects, the highest quartile (Q4) the lowest quartile (Q1) of KCNMA1_CpG_5 methylation levels were significantly correlated with lung cancer (for subjects over 55 years: OR=2.60, 95% : 1.25-5.41, =0.011; for female subjects: OR=2.09, 95% : 1.03?4.26, =0.042). From Q2 to Q4 of KCNMA1_CpG_5 methylation levels, their correlation with lung cancer became gradually stronger (=0.003 and 0.038, respectively). In male subjects, the OR of Q4 of KCNMA1_CpG_5 methylation levels was 0.35 in patients with lung cancer as compared with patients with benign nodules (95% : 0.16-0.79, =0.012). KCNMA1_CpG_3 methylation level was significantly lower in invasive adenocarcinoma than in noninvasive adenocarcinoma (=0.028), and that of KCNMA1_CpG_1 was significantly higher in patients with larger tumors (T2-4) than in those with smaller tumors (T1) (=0.021).
CONCLUSION
The change of peripheral blood methylation level is correlated with the occurrence and development of lung cancer.
目的
探讨外周血基因甲基化水平与肺癌的关联。
方法
采用基质辅助激光解吸电离飞行时间质谱法（MALDI-TOF-MS）对285例肺癌患者、186例年龄和性别匹配的良性肺结节患者以及278例匹配的健康对照者进行基因中4个CpG位点甲基化水平的定量检测。使用经协变量调整的逻辑回归模型分析甲基化水平与肺癌的关联。采用Mann-Whitney U检验比较肺癌患者不同亚组中的甲基化水平。
结果
在55岁以上人群和女性受试者中，KCNMA1_CpG_5甲基化水平的最高四分位数（Q4）与最低四分位数（Q1）与肺癌显著相关（55岁以上人群：OR=2.60，95%CI：1.25-5.41，P=0.011；女性受试者：OR=2.09，95%CI：1.03-4.26，P=0.042）。从KCNMA1_CpG_5甲基化水平的Q2到Q4，它们与肺癌的相关性逐渐增强（P分别为0.003和0.038）。在男性受试者中，与良性结节患者相比，肺癌患者中KCNMA1_CpG_5甲基化水平Q4的OR为0.35（95%CI：0.16-0.79，P=0.012）。KCNMA1_CpG_3甲基化水平在浸润性腺癌中显著低于非浸润性腺癌（P=0.028），而KCNMA1_CpG_1在肿瘤较大（T2-4）的患者中显著高于肿瘤较小（T1）的患者（P=0.021）。
结论
外周血甲基化水平的变化与肺癌的发生发展相关。
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