title: Methylated DLX4 Predicts Response to Pathologic Stage I Non-Small Cell Lung Cancer Resection.
abstract: BACKGROUND
  Surgery with curative intent is the standard treatment for patients with stage I non-small cell lung cancer (NSCLC). Even after curative resection, however, many patients have recurrent disease. Thus, there is a need to identify molecular biomarkers for the biological characteristics and prognosis of tumors.
  
  
  METHODS
  Methylation-specific polymerase chain reaction analysis was performed for the distal-less homeobox 4 (DLX4) gene in cancer tissues from 109 patients who underwent curative resection for pathologic stage I NSCLC from June 2005 to November 2011. We investigated possible correlations between DLX4 methylation status and disease outcome.
  
  
  RESULTS
  Methylated DLX4 was detected in 54 of 109 patients (49.5%). No significant relationship between DLX4 methylation status and clinicopathologic features was found. Multivariate logistic regression analysis revealed that DLX4 methylation was an independent risk factor for recurrence (p < 0.0001). Patients with DLX4 methylation showed significantly poorer recurrence-free, cancer-specific, and overall survival than patients without DLX4 methylation (p < 0.0001, p = 0.0001, p = 0.0004, respectively). Cox's proportional hazard regression analysis revealed that DLX4 methylation was an independent risk factor for poor prognosis regarding recurrence-free, cancer-specific, and overall survival (p < 0.0001, p = 0.0005, p = 0.0018, respectively).
  
  
  CONCLUSIONS
  Methylated DLX4 is a potential biomarker that predicts poor prognosis after curative resection of pathologic stage I NSCLC. Identification of patients with methylated DLX4 may assist stratification for appropriate adjuvant treatment strategies.
authors.affiliation: Department of Respiratory Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan; Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan. Electronic address: haradah@kure-nh.go.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Harada
authors.affiliation: Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan; Department of Surgery, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Department of Respiratory Surgery, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan; Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Institute for Clinical Research, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Hiroshima, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Taniyama
authors.affiliation: Department of Surgery, Hiroshima University, Hiroshima, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.affiliation: Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
authors.forename: Morihito
authors.initials: M
authors.lastname: Okada
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000473:pathology; D009367:Neoplasm Staging; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C105304:DLX4 protein, human; D005819:Genetic Markers; D018398:Homeodomain Proteins; D014157:Transcription Factors