title: Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma.
abstract: Lung adenocarcinoma is one of the most frequent causes of malignant pleural effusions (MPE). The presence of MPE bears a poor prognosis. Although epigenetic changes are commonly related to human neoplasia, scarce date is available on patients with MPE. We aimed to estimate the prognostic value of DNA methylation of tumor suppressor genes from pleural fluid. Thirty patients with MPE due to lung adenocarcinoma were prospectively included. Methylation-specific (MS) PCR was used to study the methylation status of the promoter region of tumor suppressor genes p16/INK4a, MGMT, BRCA1 and RARβ in pleural fluid. Clinical data and survival were collected. Survival analysis was performed using Kaplan-Meier plots and Cox regression. Hypermethylation in at least one gene was detected in 25 patients (83.3%). On multivariate analysis factors significantly associated with shorter survival were the lack of hypermethylation in any of the studied genes (hazard ratio = 9.3; p = 0.001), Charlson index ≥ 3 (hazard ratio = 9.6, p = 0.002) and no oncological treatment (hazard ratio = 11.1; p < 0.001). Analysis of aberrant promoter hypermethylation of tumor suppressor genes may be useful in predicting prognosis, but further studies are needed to validate our findings.
authors.affiliation: Bronchopleural Unit, Respiratory and Infectious Disease Research Group, Pneumology Service of Complexo Hospitalario Universitario de Vigo, Bio-medical Research Institute of Vigo, Vigo, Spain. maria.isabel.botana.rial@sergas.es
authors.forename: Maribel
authors.initials: M
authors.lastname: Botana-Rial
authors.forename: Loretta
authors.initials: L
authors.lastname: De Chiara
authors.forename: Diana
authors.initials: D
authors.lastname: Valverde
authors.forename: Virginia
authors.initials: V
authors.lastname: Leiro-Fernández
authors.forename: Cristina
authors.initials: C
authors.lastname: Represas-Represas
authors.forename: Victor
authors.initials: V
authors.lastname: Del Campo-Pérez
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Villar
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016066:Pleural Effusion, Malignant / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D018168:Receptors, Retinoic Acid / Q000235:genetics; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C082925:retinoic acid receptor beta; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes