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DOI: 10.1055/s-0038-1639999
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.
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No conflict of interest has been declared by the author(s).
Publikationsverlauf
Publikationsdatum:
18. April 2018 (online)
© 2018. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Georg Thieme Verlag KG
Stuttgart · New York