Qiao Rong, Di Feifei, Wang Jun, Wei Yujie, Zhang Yanman, Xu Tian, Wang Yue, Gu Wanjian, Han Baohui, Yang Rongxi
Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai 200030, People's Republic of China.
Department of Research and Academic, Nanjing TANTICA Biotechnology Co. Ltd, Nanjing 210000, People's Republic of China.
Cancer Manag Res. 2020 Nov 2;12:11063-11075. doi: 10.2147/CMAR.S275321. eCollection 2020.
Early detection is essential to improve the survival and life quality of lung cancer (LC) patients. Changes of peripheral blood DNA methylation could be associated with malignancy but were mostly studied in Caucasians.
Here, in a Chinese population, we performed mass spectrometry assays to investigate the association between very early stage LC and methylation levels of RAPSN in the peripheral blood by a case-control cohort using of 221 LC patients (93.2% LC at stage I) and 285 unrelated cancer free control individuals.
The odds ratios (ORs) of all CpG sites were evaluated for their risk to LC using inter-quartile analyses by logistic regression. In general, we observed an association between very early LC and decreased methylation of RAPSN_CpG_1.15 and RAPSN_CpG_3.4 (referring to Q4, OR range from 1.64 to 1.81, <0.05). Stratified by gender, while hypomethylation of RAPSN_CpG_1.15, RAPSN_CpG_3.4 and RAPSN_CpG_7.14 were associated with LC in males (referring to Q4, ORs range from 1.94 to 2.31, <0.05), RAPSN_CpG_2 and RAPSN_CpG_5 showed significantly lower methylation in female LC patients comparing to controls (referring to Q4, ORs range from 2.49 to 3.60, <0.05). The risk of RAPSN hypomethylation to LC was enhanced by aging, and typically for people older than 55 years (referring to Q4, ORs range from 2.17 to 3.61 in six out of all 10 analyzed CpG groups, <0.05).
Our study reveals an association between RAPSN hypomethylation in peripheral blood and LC and suggests the occurrence of altered blood-based methylation at the early stage of cancer.
早期检测对于提高肺癌（LC）患者的生存率和生活质量至关重要。外周血DNA甲基化的变化可能与恶性肿瘤相关，但大多是在白种人中进行研究。
在此，在中国人群中，我们通过病例对照队列研究，对221例LC患者（93.2%为I期LC）和285名无癌症的无关对照个体进行质谱分析，以研究极早期LC与外周血中RAPSN甲基化水平之间的关联。
通过逻辑回归的四分位数分析评估所有CpG位点对LC的风险比值（OR）。总体而言，我们观察到极早期LC与RAPSN_CpG_1.15和RAPSN_CpG_3.4甲基化降低之间存在关联（参考Q4，OR范围为1.64至1.81，<0.05）。按性别分层，虽然RAPSN_CpG_1.15、RAPSN_CpG_3.4和RAPSN_CpG_7.14的低甲基化与男性LC相关（参考Q4，OR范围为1.94至2.31，<0.05），但与对照组相比，女性LC患者中RAPSN_CpG_2和RAPSN_CpG_5的甲基化显著降低（参考Q4，OR范围为2.49至3.60，<0.05）。RAPSN低甲基化对LC的风险随年龄增长而增加，通常在55岁以上人群中（参考Q4，在所有10个分析的CpG组中的6个组中，OR范围为2.17至3.61，<0.05）。
我们的研究揭示了外周血中RAPSN低甲基化与LC之间的关联，并表明在癌症早期阶段存在基于血液的甲基化改变。
