ArticlePloS one2018
Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- New insights into RAS in head and neck cancer.Biochimica et biophysica acta. Reviews on cancer · 2023Review
- DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer.International journal of molecular sciences · 2023Review
- PITX1 plays essential functions in cancer.Frontiers in oncology · 2023Review
- Gene body methylation in cancer: molecular mechanisms and clinical applications.Clinical epigenetics · 2022Review
- Article
- Multi-Omics Investigations Revealed Underlying Molecular Mechanisms Associated With Tumor Stiffness and Identified Sunitinib as a Potential Therapy for Reducing Stiffness in Pituitary Adenomas.Frontiers in cell and developmental biology · 2022Article
- Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs.Endocrinology · 2021Review
- Article
- Bioinformatics analysis of prognostic value of PITX1 gene in breast cancer.Bioscience reports · 2020Article
- DNA methylation profiling to predict recurrence risk in stage Ι lung adenocarcinoma: Development and validation of a nomogram to clinical management.Journal of cellular and molecular medicine · 2020Article
- Evaluation of C5orf66-AS1 as a Potential Biomarker for Predicting Early Gastric Cancer and Its Role in Gastric Carcinogenesis.OncoTargets and therapy · 2020Article
- Integrated analysis reveals potential long non-coding RNA biomarkers and their potential biological functions for disease free survival in gastric cancer patients.Cancer cell international · 2019Article
- Classification of early and late stage liver hepatocellular carcinoma patients from their genomics and epigenomics profiles.PloS one · 2019Article
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with squamous cell cancer of the head and neck region (HNSCC) are at risk for disease recurrence and metastases, even after initial successful therapy. A tissue-based biomarker could be beneficial to guide treatment as well as post-treatment surveillance. Gene methylation status has been recently identified as powerful prognostic biomarker in HNSCC. We therefore evaluated the methylation status of the homeobox gene PITX1 and the adjacent long intergenic non-coding RNA (lincRNA) C5orf66-AS1 in publicly available datasets.
methodsGene methylation and expression data from 528 patients with HNSCC included in The Cancer Genome Atlas (TCGA, there obtained by using the Infinium HumanMethylation450 BeadChip Kit) were evaluated and methylation and expression levels of PITX1 and lincRNA C5orf66-AS1 was correlated with overall survival and other parameters. Thus, ten beads targeting PITX1 exon 3 and three beads targeting lincRNA C5orf66-AS1 were identified as significant candidates. The mean methylation of these beads was used for further correlation and the median was employed for dichotomization.
resultsBoth PITX1 exon 3 and lincRNA C5orf66-AS1 were significantly higher methylated in tumor tissue than in normal adjacent tissue (NAT) (PITX1 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 (HR): 4.97 [1.78-16.71], p = 0.010, lincRNA C5orf66-AS1: Hazard ratio (HR): 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, human papilloma virus (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 as well in a subgroup of HPV-negative tumors (p = 0.003) and in patients with laryngeal tumors (p = 0.022).
conclusionMethylation status of PITX1 and even more so of lincRNA C5orf66-AS1 is a promising prognostic biomarker in HNSCC, in particular for HPV-negative patients. Further prospective evaluation is warranted.
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