Genome-wide Identification of a Methylation Gene Panel as a Prognostic Biomarker in Nasopharyngeal Carcinoma
Menée initialement à partir d'échantillons de tissu tumoral et de tissu sain prélevés sur 24 patients atteints d'un carcinome du rhinopharynx, puis validée sur 454 patients complémentaires, cette étude identifie un panel de 6 gènes dont l'hyperméthylation est associée à la survie des patients
DNA methylation, the best known epigenetic marker, can be used as a prognostic biomarker in many cancers. We examined DNA methylation status and survival in nasopharyngeal carcinoma (NPC) patients. Aberrant DNA methylated genes in 24 NPC tissues and 24 non-cancer nasopharyngitis biopsy tissues (NCNBT) were identified using Illumina 450K BeadChip. Correlations between DNA methylation and clinical outcomes were evaluated using bisulfite pyrosequencing in 454 NPC patients. Genome-wide methylation analysis demonstrated that NPC tissues had distinct DNA methylation patterns compared to NCNBT. Among all significant CpG sites, 2173 CpG sites with β change≥0.2 (1880 hypermethylated, 293 hypomethylated) were identified (P<0.05). A methylation gene panel comprising six hypermethylated genes was constructed with the average Z-score method. Patients in the training cohort with high methylation had poorer disease-free survival (DFS, hazards ratio [HR] =2.26, 95% confidence interval [CI]=1.28-4.01, P=0.005) and overall survival (OS, HR=2.47, 95% CI=1.30-4.71, P=0.006) than those with low methylation. There were similar results in the validation (DFS, HR=2.07, 95% CI=1.17-3.67, P=0.013; OS, HR=1.83, 95% CI=1.01-3.31, P=0.046) and independent cohorts (DFS, HR=1.94, 95% CI=1.08-3.47, P=0.026; OS, HR=2.09, 95% CI=1.10-3.98, P=0.022). Analysis indicated that the methylation gene panel was an independent prognostic factor. Furthermore, patients with low methylation had a favorable response to concurrent chemotherapy with an improved DFS (P=0.045) and OS (P=0.031); whereas patients with high methylation did not benefit from concurrent chemotherapy. The 6-hypermethylated gene panel was associated with poor survival in patients with NPC, demonstrating its potential usefulness as a prognostic biomarker to clinicians in NPC management.
Molecular Cancer Therapeutics , résumé, 2015