PITX1 and the long non-coding RNA C5orf66-AS1 DNA methylation as prognostic biomarkers in patients with head and neck squamous cell carcinomas

Background:

Tissue-based biomarker are considered to influence treatment decision of HNSCC as well as post-treatment followup. Gene methylation status has been recently identified as prognostic biomarker. We evaluated the methylation status of the homeobox gene PITX1 and the adjacent long intergenic non-coding RNA (lincRNA) C5orf66-AS1.

Methods:

Gene methylation and expression data from 528 patients with HNSCC included in The Cancer Genome Atlas were evaluated and methylation and expression levels of PITX1 and lincRNA C5orf66-AS1 were correlated with overall survival and other parameters. Thus, ten beads targeting PITX1 exon 3 and three beads targeting lincRNA C5orf66-AS1 were identified as candidates.

Results:

Both PITX1 exon 3 and lincRNA C5orf66-AS1 were significantly higher methylated in tumor tissue than in normal adjacent tissue (NAT) (exon 3: tumor tissue 58.1%, NAT: 31.7%, p < 0.001; lincRNA C5orf66-AS1: tumor tissue: 27.4%, NAT: 18.9%, p < 0.001). In a univariate analysis, hypermethylation of both loci was significantly associated with the risk of death (univariate: exon 3: Hazard ratio: 4.97 [1.78 – 16.71], p = 0.010, lincRNA C5orf66-AS1: Hazard ratio: 12.23 [3.01 – 49.74], p < 0.001). PITX1 exon 3 and lincRNA C5orf66-AS1 methylation was also significantly correlated with tumor localization, T category, HPV-negative and p16-negative tumors and tumor grade. Kaplan-Meier analysis showed, that lincRNA C5orf66-AS1 hypomethylation was significantly associated with overall survival (p = 0.001) in the entire cohort.

Conclusion:

Methylation status of PITX1 and even more so of lincRNA C5orf66-AS1 is a promising prognostic biomarker in HNSCC which might influence treatment decision of HNSCC.

Publication History

Publication Date:
18 April 2018 (online)