domingo, 24 de junio de 2018

Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients. - PubMed - NCBI

Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients. - PubMed - NCBI



 2018 Apr 27;9(11):1885-1895. doi: 10.7150/jca.23239. eCollection 2018.

Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients.

Abstract

Purpose: Although oral squamous cell carcinoma (OSCC) presents great mortality and morbidity worldwide, the mechanisms behind its clinical behavior remain unclear. Biomarkers are needed to forecast patients' survival and, among those patients undergoing curative therapy, which are more likely to develop tumor recurrence/metastasis. Demonstrating clinical relevance of these biomarkers could be crucial both for surveillance and in helping to establish adjuvant therapy strategies. We aimed to identify genomic and epigenetic biomarkers of OSCC prognosis as well as to explore a noninvasive strategy to perform its detection. Methods: OSCC tumor and non-tumor tissue samples and cells scrapped from the tumor surface were genomic and epigenetically evaluated by Methylation-Specific Multiplex Ligation-dependent Probe Amplification technique. Results: Copy number alterations in ATM, CASR, TP73, CADM1, RARB, CDH13, PAX5RB1 genes and GATA5, PAX6, CADM1 and CHFR promoter methylation were shown to be associated with worse OSCC patients' survival. Copy number alterations in BRCA1, CDKN2A, CHFR, GATA5, PYCARD, STK11, TP53, VHL genes and GATA5, CADM1, KLLN, MSH6, PAX5WT1promoter methylation were shown to be associated with development of metastasis/relapses during or after OSCC patients' treatment. We also found a good agreement in the status of CDKN2A promoter methylation evaluated noninvasively or in the tumor tissue. Conclusions:Genomic and epigenetic signatures were validated in a larger and geographically separate cohort, from TCGA database, which reinforce their clinical applicability. Noninvasive methodologies for detection of these signatures require further studies before translation in to clinical practice.

KEYWORDS:

Copy number alterations; biomarkers, OSCC survival, recurrence, TCGA data; methylation

PMID:
 
29896272
 
PMCID:
 
PMC5995936
 
DOI:
 
10.7150/jca.23239

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