title: Predictive factors for the sensitivity of radiotherapy and prognosis of esophageal squamous cell carcinoma.
abstract: OBJECTIVE
  To identify predictive biomarkers for radiosensitization and prognosis of esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  A total of 150 advanced stage ESCC patients were treated with preoperative radiotherapy. The protein levels of Dicer 1, DNA methyltransferase 1 (Dnmt1), and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and the mRNA levels of Dicer 1, Dnmt1, and let-7b microRNA (miRNA) were measured in ESCC tumor tissues before and after radiotherapy. Global DNA methylation was measured and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed.
  
  
  RESULTS
  Negative Dicer 1, Dnmt1, and DNA-PKcs protein expression were observed in 72%, 67.3%, and 50.7% of ESCC patients, respectively. Primary Dicer 1 and Dnmt1 expression positively correlated with radiation sensitization and longer survival of ESCC patients, while increased Dicer 1 and Dnmt1 expression after radiation correlated with increased apoptosis in residual tumor tissues. Dicer 1 and Dnmt1 expression correlated with let-7b miRNA expression and global DNA methylation levels, respectively. In contrast, positive DNA-PKcs expression negatively correlated with radiation-induced pathological reactions, and increased DNA-PKcs expression correlated with increased apoptosis after radiation.
  
  
  CONCLUSIONS
  Global DNA hypomethylation and low miRNA expression are involved in the sensitization of ESCC to radiotherapy and prognosis of patients with ESCC.
authors.affiliation: Department of General Surgery.
authors.forename: Shaobin
authors.initials: S
authors.lastname: Wu
authors.forename: Xianwei
authors.initials: X
authors.lastname: Wang
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D011836:Radiation Tolerance; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases