全基因组DNA甲基化测量可预测非小细胞肺癌化疗的生存获益。
Measurement of genome-wide DNA methylation predicts survival benefits from chemotherapy in non-small cell lung cancer.
作者信息
Mo Min-Li, Ma Jie, Chen Zhao, Wei Bing, Li Hui, Zhou Yong, Shi Huaiyin, Tolani Bhairavi, Jin Joy Q, Tseng Hsin-Hui, Shen Dong, Zhan Yi, Li Jun, Jablons David M, Zhang Rong-Qing, Guo Yongjun, He Biao, Zhou Hai-Meng
机构信息
School of Life Sciences, Tsinghua University, Beijing, 10084, China.
出版信息
J Cancer Res Clin Oncol. 2015 May;141(5):901-8. doi: 10.1007/s00432-014-1860-7. Epub 2014 Nov 4.
PURPOSE
Novel molecular predictive biomarkers for chemotherapy have been screened and validated in non-small cell lung cancer (NSCLC). However, there was no report on the correlation of genome-wide DNA methylation with survival benefit from chemotherapy in NSCLC.
METHODS
A sandwich enzyme-linked immunosorbent assay (ELISA) method was first established, optimized and validated. A total of 191 NSCLC samples were analyzed using the sandwich ELISA for the association between the relative genome-wide DNA methylation level and the survival outcomes from chemotherapy.
RESULTS
The analytical performance of the sandwich ELISA method was satisfying and suitable for analysis. Using the sandwich ELISA method, we found that the genome-wide DNA methylation level in NSCLC cancer tissues was significantly lower than that in adjacent normal tissues, which further validated the assay. We found that there was no significant correlation between genome-wide DNA methylation level and patients' histology, stage and progression free survivals. However, in patients with high methylation level, those without chemotherapy had significantly better overall survival than those receiving chemotherapy. In patients receiving chemotherapy, those with low genome-wide DNA methylation level had significantly better overall survival than those with relatively high DNA methylation level.
CONCLUSIONS
Genome-wide DNA hypomethylation as a sign of genomic instability may predict overall survival benefit from chemotherapy in NSCLC.
目的
已在非小细胞肺癌（NSCLC）中筛选并验证了用于化疗的新型分子预测生物标志物。然而，关于全基因组DNA甲基化与NSCLC化疗生存获益之间的相关性尚无报道。
方法
首先建立、优化并验证了一种夹心酶联免疫吸附测定（ELISA）方法。使用该夹心ELISA对总共191份NSCLC样本进行分析，以研究全基因组DNA甲基化相对水平与化疗生存结果之间的关联。
结果
夹心ELISA方法的分析性能令人满意且适用于分析。使用该夹心ELISA方法，我们发现NSCLC癌组织中的全基因组DNA甲基化水平显著低于相邻正常组织，这进一步验证了该检测方法。我们发现全基因组DNA甲基化水平与患者的组织学、分期和无进展生存期之间无显著相关性。然而，在甲基化水平高的患者中，未接受化疗的患者总生存期明显优于接受化疗的患者。在接受化疗的患者中，全基因组DNA甲基化水平低的患者总生存期明显优于DNA甲基化水平相对较高的患者。
结论
全基因组DNA低甲基化作为基因组不稳定的标志，可能预测NSCLC化疗的总生存获益。
Zotero 插件