Hypermethylation of collagen alpha 2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer

Objectives: Collagen production plays a role in the development of tumors from cancer cells. The aim of the present study is to examine the involvement of epigenetic alteration of Collagen alpha 2 (I) (COL1A2) gene expression in cases of head and neck squamous cell carcinoma (HNSCC). Methods: COL1A2 expression was examined in a panel of cell lines using RT-PCR. The methylation status of the COL1A2 promoter was studied using bisulfate sequencing and methylation-specific PCR (MSP). Results: COL1A2 expression was absent in 6 of 11 (54.5%) UM-SCC cell lines, whereas three nonmalignant cell lines had stable expressions. MSP analysis showed that 46/98 (46.9%) contained methylated alleles. COL1A2 methylation was significantly correlated with tumor size (P = 0.041), lymph node status (P = 0.008), tumor stage (P = 0.011), H-cadherin methylation (P = 0.039) and disease-free survival (P = 0.005). On multivariate Cox proportional hazard regression, which included age, sex, smoking status, and alcohol exposure, both tumor stage and COL1A2 methylation remained independent prognostic factors. Conclusions: This study suggests that CpG hypermethylation is a likely mechanism of COL1A2 gene inactivation, supporting the hypothesis that the COL1A2 gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker.