Universität zu Köln

Sailer, Verena, Gevensleben, Heidrun, Dietrich, Joern, Goltz, Diane, Kristiansen, Glen, Bootz, Friedrich and Dietrich, Dimo (2017). Clinical performance validation of PITX2 DNA methylation as prognostic biomarker in patients with head and neck squamous cell carcinoma. PLoS One, 12 (6). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Background Despite advances in combined modality therapy, outcomes in head and neck squamous cell cancer (HNSCC) remain dismal with five-year overall survival rates of less than 50%. Prognostic biomarkers are urgently needed to identify patients with a high risk of death after initial curative treatment. Methylation status of the paired-like homeodomain transcription factor 2 (PITX2) has recently emerged as a powerful prognostic biomarker in various cancers. In the present study, the clinical performance of PITX2 methylation was validated in a HNSCC cohort by means of an independent analytical platform (Infinium HumanMethylation450 BeadChip, Illumina, Inc.). Methods A total of 528 HNSCC patients from The Cancer Genome Atlas (TCGA) were included in the study. Death was defined as primary endpoint. PITX2 methylation was correlated with overall survival and clinicopathological parameters. Results PITX2 methylation was significantly associated with sex, tumor site, p16 status, and grade. In univariate Cox proportional hazards analysis, PITX2 hypermethylation analyzed as continuous and dichotomized variable was significantly associated with prolonged overall survival of HNSCC patients (continuous: hazard ratio (HR) = 0.19 [95% CI: 0.04-0.88], p = 0.034; dichotomized: HR = 0.52 [95% CI: 0.33-0.84], p = 0.007). In multivariate Cox analysis including established clinicopathological parameters, PITX2 promoter methylation was confirmed as prognostic factor (HR = 0.28 [95% CI: 0.09-0.84], p = 0.023). Conclusion Using an independent analytical platform, PITX2 methylation was validated as a prognostic biomarker in HNSCC patients, identifying patients that potentially benefit from intensified surveillance and/or administration of adjuvant/neodjuvant treatment, i.e. immunotherapy.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sailer, Verena UNSPECIFIED UNSPECIFIED UNSPECIFIED Gevensleben, Heidrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietrich, Joern UNSPECIFIED UNSPECIFIED UNSPECIFIED Goltz, Diane UNSPECIFIED UNSPECIFIED UNSPECIFIED Kristiansen, Glen UNSPECIFIED UNSPECIFIED UNSPECIFIED Bootz, Friedrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietrich, Dimo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-227635
DOI:	10.1371/journal.pone.0179412
Journal or Publication Title:	PLoS One
Volume:	12
Number:	6
Date:	2017
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PROSTATE-CANCER PATIENTS; POSITIVE BREAST-CANCER; HUMAN-PAPILLOMAVIRUS; OROPHARYNGEAL CANCER; ANTIGEN RECURRENCE; TUMORS. HIGHLIGHTS; RISK; CHEMOTHERAPY; MULTICENTER; HYPERMETHYLATION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22763