Genome-Wide Identification of a Methylation Gene Panel as a Prognostic Biomarker in Nasopharyngeal Carcinoma.

Abstract

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 noncancer 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 with NCNBT. Among all significant CpG sites, 2,173 CpG sites with β change ≥ 0.2 (1,880 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, 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 six-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.

• Authors: Wei Jiang, Na Liu, Xiao-Zhong Chen, Ying Sun, Bin Li, Xian-Yue Ren, Wei-Feng Qin, Ning Jiang, Ya-Fei Xu, Ying-Qin Li, Jian Ren, William C S Cho, Jing-Ping Yun, Jing Zeng, Li-Zhi Liu, Li Li, Ying Guo, Hai-Qiang Mai, Mu-Sheng Zeng, Tie-Bang Kang, Wei-Hua Jia, Jian-Yong Shao, Jun Ma
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 14 Issue 12 Pg. 2864-73 (Dec 2015) ISSN: 1538-8514 [Electronic] United States
• PMID: 26443805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Neoplasm Proteins

Topics

• Adolescent
• Adult
• Aged
• Biomarkers, Tumor (genetics)
• Carcinoma
• DNA Methylation (genetics)
• Disease-Free Survival
• Female
• Genome, Human
• Humans
• Male
• Middle Aged
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms (genetics, pathology)
• Neoplasm Proteins (genetics)
• Neoplasm Staging
• Prognosis
• Promoter Regions, Genetic