Analysis of Site-Specific Methylation of Tumor-Related Genes in Head and Neck Cancer: Potential Utility as Biomarkers for Prognosis

Abstract

Clarifying the epigenetic regulation of tumor-related genes (TRGs) can provide insights into the mechanisms of tumorigenesis and the risk for disease recurrence in HPV-negative head and neck cancers, originating in the hypopharynx, larynx, and oral cavity. We analyzed the methylation status of the promoters of 30 TRGs in 178 HPV-negative head and neck cancer patients using a quantitative methylation-specific PCR. Promoter methylation was correlated with various clinical characteristics and patient survival. The mean number of methylated TRGs was 14.2 (range, 2–25). In the multivariate Cox proportional hazards analysis, the methylation of COL1A2 and VEGFR1 was associated with poor survival for hypopharyngeal cancer, with hazard ratios: 3.19; p = 0.009 and 3.07; p = 0.014, respectively. The methylation of p16 and COL1A2 were independent prognostic factors for poor survival in laryngeal cancer (hazard ratio: 4.55; p = 0.013 and 3.12; p = 0.035, respectively). In patients with oral cancer, the methylation of TAC1 and SSTR1 best correlated with poor survival (hazard ratio: 4.29; p = 0.005 and 5.38; p = 0.029, respectively). Our findings suggest that methylation status of TRGs could serve as important site-specific biomarkers for prediction of clinical outcomes in patients with HPV-negative head and neck cancer.

Prognostic significance of abnormal matrix collagen remodeling in colorectal cancer based on histologic and bioinformatics analysis

“…The effects of these coding genes on CRC prognosis were comprehensively analyzed, and a prognostic model of CRC was constructed with six mRNA signatures (COL1A1, COL1A2, COL3A1, COL4A3, COL4A6 and MMP2). Among them, COL1A1, COL1A2, COL3A1 and MMP2 have been reported to serve vital roles in tumor invasion, and are thus associated with poor prognosis (54)(55)(56)(57). COL4A3 and COL4A6, encoding COL IV alpha chains 3 and 6, respectively, are required for correct basement membrane (BM) formation, and mutations within these genes affect BM stability (58,59).…”

Association of TET3 epigenetic inactivation with head and neck cancer

“…The analysis was performed using Thermal Cycler Dice Real Time System TP800 software (version 1.03A), according to the manufacturer's instructions [ 38 ]. To analyze the methylation status of CCBE1 [ 39 ], SALL3 [ 40 ], TAC1 [ 41 ], DCC [ 42 ], GALR1 [ 43 ], DAPK [ 44 ], COL1A2 [ 45 ], GALR2 [ 43 ], CDH1 [ 46 ], RASSF1A [ 46 ], MGMT [ 44 ], CDH13 [ 47 ], and p16 [ 46 ], primers and conditions were as previously described.…”

Circular RNAs and their roles in head and neck cancers

“…This is because HNCs are relatively heterogeneous diseases that occur in complex anatomical structures, and different etiological factors and pathological and biological molecular changes are responsible for different subtypes of HNCs [148,149]. For example, the loss of expression of common fragile site genes [150] and Poor overall survival, poor radiosensitivity and serve as independent prognostic factors (HR = 3.03, p = 0.02) [147] Note: HNSCC head and neck squamous cell carcinoma, OSCC oral squamous cell carcinoma, LSCC laryngeal squamous cell carcinoma, NPC nasopharyngeal carcinoma, "-" means unannotated or not investigated in the paper, "*" means based on speculation but not validated clinically methylation of tumor-related genes [151] presented site-specificity in different subtypes of HNCs. Given the differentially expressed miRNAs in HNCs located at various places [152] and the tissue-specificity of cir-cRNAs, the circRNAs in HNCs may be differentially dysregulated according to the site of the primary tumor (Table 4).…”