title: Combined Effect of Metastasis-Related MicroRNA, miR-34 and miR-124 Family, Methylation on Prognosis of Non-Small-Cell Lung Cancer.
abstract: Many patients with non-small-cell lung cancer (NSCLC) still develop tumor metastasis and recurrence after pulmonary resection and are the primary causes of lung cancer treatment failure and death. MicroRNAs (miRs) have central roles during tumor metastasis and many miR genes are potentially subjected to control by DNA methylation in multiple tumor types. Recently, miR-34 and miR-124 have been demonstrated as potential regulators of the metastasis process in several cancer types.
  
  
  
  We studied the methylation status of miR-34 and miR-124 families in 157 patients with NSCLC using methylation-specific polymerase chain reaction and evaluated the clinical effect of their methylation on the patients' prognosis.
  
  
  
  Methylation was detected in 30.6% for miR-34a, 40.8% for miR-34b/c, 30.6% for miR-124-1, 49.7% for miR-124-2, and 51.6% for miR-124-3 in NSCLC tissue. miR-34b/c methylation was significantly associated with age, gender, smoking status, histologic type, and pathologic stage. miR-34b/c, miR-124-2, and miR-124-3 methylation were significantly associated with worse survival in all patients (adjusted hazard ratio [HRadj] for miR-34b/c, 3.34; 95% confidence interval [CI], 1.95-5.74; P < .0001; HRadjfor miR-124-2, 1.99; 95% CI, 1.19-3.32; P = .009; and HRadjfor miR-124-3, 2.10; 95% CI, 1.24-3.55; P = .006). When miR-34b/c and miR-124-3 methylation were combined, overall survival decreased as the number of methylations increased (Ptrend< .0001).
  
  
  
  These findings suggest that miR-34 and miR-124 loci methylation could be a tumor-associated frequent event during NSCLC tumorigenesis and could be used as powerful markers for the prognosis of patients with NSCLC.
authors.affiliation: Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Preventive Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Thoracic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Eung Bae
authors.initials: EB
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Konyang University Hospital, Daejeon, Republic of Korea.
authors.forename: Ji Woong
authors.initials: JW
authors.lastname: Son
authors.affiliation: Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: doskim@knu.ac.kr.
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: jaeyong@knu.ac.kr.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000556:secondary; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C509207:MIRN124 microRNA, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: MSP; MicroRNA-124; MicroRNA-34; NSCLC; Prognosis