Objective: To explore the association of KCNMA1 gene methylation levels in peripheral blood with lung cancer.
Methods: The methylation levels of 4 CpG sites in KCNMA1 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 KCNMA1 methylation levels with lung cancer was analyzed using logistic regression models adjusted for covariates. The KCNMA1 methylation levels in different subgroups of lung cancer patients were compared using Mann-Whitney U test.
Results: In subjects over 55 years and in female subjects, the highest quartile (Q4) vs 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% CI: 1.25-5.41, P=0.011; for female subjects: OR=2.09, 95% CI: 1.03?4.26, P=0.042). From Q2 to Q4 of KCNMA1_CpG_5 methylation levels, their correlation with lung cancer became gradually stronger (P=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% CI: 0.16-0.79, P=0.012). KCNMA1_CpG_3 methylation level was significantly lower in invasive adenocarcinoma than in noninvasive adenocarcinoma (P=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) (P=0.021).
Conclusion: The change of peripheral blood KCNMA1 methylation level is correlated with the occurrence and development of lung cancer.
目的: 探究外周血中KCNMA1基因的甲基化水平与肺癌的相关性。
方法: 应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术对285例肺癌患者、186例年龄、性别匹配的良性肺结节患者和278例匹配的健康对照外周血中KCNMA1基因上4个CpG位点甲基化水平进行半定量检测。使用Logistic回归模型校正协变量分析DNA甲基化水平与肺癌的相关性。使用Mann-Whitney U检验分析不同临床特征组别的甲基化水平差异。
结果: 在>55岁和女性人群中，KCNMA1_CpG_5甲基化水平最高四分位Q4 vs最低四分位Q1均与肺癌显著相关(>55岁人群：OR=2.60，95% CI: 1.25~5.41，P=0.011；女性人群：OR=2.09，95% CI: 1.03~4.26，P=0.042)，且KCNMA1_CpG_5甲基化的相关性从Q2到Q4逐渐增强(P=0.003，0.038)。与良性患者相比，KCNMA1_CpG_5最高四分位Q4在男性肺癌患者中的OR值为0.35(95% CI: 0.16~0.79，P=0.012)。浸润性腺癌中KCNMA1_CpG_3甲基化水平显著低于非浸润性腺癌(P=0.028)，较大肿瘤(T2-4)中KCNMA1_CpG_1甲基化水平显著高于较小肿瘤(T1)(P=0.021)。
结论: 外周血中KCNMA1甲基化水平的改变可能与肺癌发生和发展相关。
Keywords: DNA methylation; KCNMA1; case-control study; lung cancer; peripheral blood.