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PurposeSurvival 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.Patients and methodsA 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.Results14-3-3sigma 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.

Original publication

DOI

10.1200/jco.2005.02.2905

Type

Journal article

Journal

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Publication Date

12/2005

Volume

23

Pages

9105 - 9112

Addresses

Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.

Keywords

Spanish Lung Cancer Group, Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Disease Progression, Cisplatin, Exonucleases, Exoribonucleases, 14-3-3 Proteins, Neoplasm Proteins, Deoxycytidine, Antineoplastic Combined Chemotherapy Protocols, Prognosis, Drug Administration Schedule, Prospective Studies, Predictive Value of Tests, DNA Methylation, Gene Silencing, Base Sequence, Genes, cdc, Molecular Sequence Data, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Biomarkers, Tumor