title: Measurement of genome-wide DNA methylation predicts survival benefits from chemotherapy in non-small cell lung cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, 10084, China.
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Mo
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Wei
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Huaiyin
authors.initials: H
authors.lastname: Shi
authors.forename: Bhairavi
authors.initials: B
authors.lastname: Tolani
authors.forename: Joy Q
authors.initials: JQ
authors.lastname: Jin
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Tseng
authors.forename: Dong
authors.initials: D
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhan
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.forename: Rong-Qing
authors.initials: RQ
authors.lastname: Zhang
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guo
authors.forename: Biao
authors.initials: B
authors.lastname: He
authors.forename: Hai-Meng
authors.initials: HM
authors.lastname: Zhou
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000235:genetics* / Q000401:mortality*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016019:Survival Analysis; D000097584:DNA Methyltransferase 3B
chemical_list: D014408:Biomarkers, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human