Methylation patterns and chemosensitivity in NSCLC.
Survival in advanced non-small-cell lung cancer (NSCLC) patients 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. 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. 14-3-3sigma methylation was observed in all histologic types in 39 patients (34%). After a median follow-up of 9.8 months, median survival was significantly longer in the methylation-positive group (15.1 vs 9.8 months; P = 0.004). Median time to progression was 8 months in the methylation-positive group, and 6.3 months in the methylation-negative group (P = 0.027 by the log-rank test). A multivariate Cox regression model identified only 14-3-3sigma methylation status and ECOG performance status (PS) as independent prognostic factors for survival. In an exploratory analysis, median survival for 22 methylation-positive responders has not been reached, while it was 11.3 months for 29 methylation-negative responders (P = 0.001). 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.
Ramírez
José Luis
JL
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Salazar
M Fernanda
MF
Gupta
Jalaj
J
Sánchez
José Miguel
JM
Taron
Miquel
M
Sanchez-Ronco
Maria
M
Alberola
Vicente
V
De las Peñas
Ramon
R
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D019175:DNA Methylation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine