title: 14-3-3sigma methylation in pretreatment serum circulating DNA of cisplatin-plus-gemcitabine-treated advanced non-small-cell lung cancer patients predicts survival: The Spanish Lung Cancer Group.
abstract: OBJECTIVE
  Survival in patients with advanced non-small-cell lung cancer (NSCLC) who are treated with platinum-based chemotherapy is rather variable. Methylation-dependent transcriptional silencing of 14-3-3sigma, a major G2-M checkpoint control gene, could be a predictor of longer survival.
  
  
  METHODS
  A sensitive methylation-specific polymerase chain reaction assay was used to evaluate 14-3-3sigma methylation status in pretreatment serum DNA obtained from 115 cisplatin-plus-gemcitabine-treated advanced NSCLC patients.
  
  
  RESULTS
  14-3-3sigma methylation was observed in all histologic types of 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 v 9.8 months; P = .004). Median time to progression was 8 months in the methylation-positive group and 6.3 months in the methylation-negative group (log-rank test, P = .027). A multivariate Cox regression model identified only 14-3-3sigma methylation status and Eastern Cooperative Oncology Group performance status as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, whereas survival was 11.3 months for 29 methylation-negative responders (P = .001). CONCLUSION Methylation of 14-3-3sigma is a new independent prognostic factor for survival in NSCLC patients receiving platinum-based chemotherapy. It can be reliably and conveniently detected in the serum, thus obviating the need for tumor tissue analysis.
authors.affiliation: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ramirez
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
authors.forename: Miquel
authors.initials: M
authors.lastname: Taron
authors.forename: Maria
authors.initials: M
authors.lastname: Sanchez-Ronco
authors.forename: Vicente
authors.initials: V
authors.lastname: Alberola
authors.forename: Ramon
authors.initials: R
authors.lastname: de Las Peñas
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Sanchez
authors.forename: Teresa
authors.initials: T
authors.lastname: Moran
authors.forename: Carlos
authors.initials: C
authors.lastname: Camps
authors.forename: Bartomeu
authors.initials: B
authors.lastname: Massuti
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Sanchez
authors.forename: Fernanda
authors.initials: F
authors.lastname: Salazar
authors.forename: Silvia
authors.initials: S
authors.lastname: Catot
mesh_terms: D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D019175:DNA Methylation; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D004334:Drug Administration Schedule; D005092:Exonucleases / Q000378:metabolism*; D005095:Exoribonucleases; D005260:Female; D020868:Gene Silencing; D018816:Genes, cdc; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D000093542:Gemcitabine
chemical_list: D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D003841:Deoxycytidine; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human; D002945:Cisplatin; D000093542:Gemcitabine