title: miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer.
abstract: MicroRNAs (miRNAs) have been identified as promising prognostic markers in non-small-cell lung cancer (NSCLC) since they play an important role in oncogenesis. The miR-34 family is composed of three miRNAs (miR-34a, miR-34b and miR-34c) that are part of the p53 network and whose expression is directly induced by p53 in response to DNA damage or oncogenic stress. We have analyzed the impact of miR-34 expression on relapse and overall survival in surgically resected NSCLC patients. For this purpose, we used stem-loop reverse transcription-polymerase chain reaction to analyze the expression of the miR-34 family in paired tumor and normal tissue from 70 surgically resected NSCLC patients who received no postsurgical treatment until relapse. In addition, in patients with sufficient tumor tissue, we assessed p53 mutations and the methylation status of the MIRN34A gene promoter region and correlated these findings with miR-34a expression. Molecular findings were correlated with relapse and overall survival. The miR-34 family was downregulated in tumor compared with normal tissue, and low levels of miR-34a expression were correlated with a high probability of relapse (P = 0.04). A relation was also found between MIRN34A methylation and miR-34a expression (P = 0.008). Patients with both p53 mutations and low miR-34a levels had the highest probability of relapse (P = 0.001). In the multivariate analysis, miR-34a expression emerged as an independent prognostic marker for relapse. In summary, we have identified miR-34a as a novel prognostic marker in NSCLC patients, providing a potential mechanism for estimating a patient's risk of disease recurrence and a useful tool to help guide treatment decisions.
authors.affiliation: Department of Medical Oncology, Hospital Clinic, Institut d'Investigacions Biomèdiques, Agust Pi i Sunyer, 08036 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gallardo
authors.forename: Alfons
authors.initials: A
authors.lastname: Navarro
authors.forename: Nuria
authors.initials: N
authors.lastname: Viñolas
authors.forename: Ramon M
authors.initials: RM
authors.lastname: Marrades
authors.forename: Tania
authors.initials: T
authors.lastname: Diaz
authors.forename: Bernat
authors.initials: B
authors.lastname: Gel
authors.forename: Angels
authors.initials: A
authors.lastname: Quera
authors.forename: Eva
authors.initials: E
authors.lastname: Bandres
authors.forename: Jesus
authors.initials: J
authors.lastname: Garcia-Foncillas
authors.forename: Jose
authors.initials: J
authors.lastname: Ramirez
authors.forename: Mariano
authors.initials: M
authors.lastname: Monzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53