RGD Reference Report - PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas. - Rat Genome Database

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PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas.

Authors: Camargo Barros-Filho, Mateus  Barreto Menezes de Lima, Larissa  Bisarro Dos Reis, Mariana  Bette Homem de Mello, Julia  Moraes Beltrami, Caroline  Lopes Pinto, Clóvis Antonio  Kowalski, Luiz Paulo  Rogatto, Silvia Regina 
Citation: Camargo Barros-Filho M, etal., Int J Mol Sci. 2019 Mar 16;20(6). pii: ijms20061334. doi: 10.3390/ijms20061334.
RGD ID: 14696825
Pubmed: PMID:30884810   (View Abstract at PubMed)
PMCID: PMC6471408   (View Article at PubMed Central)
DOI: DOI:10.3390/ijms20061334   (Journal Full-text)

Despite the low mortality rates, well-differentiated thyroid carcinomas (WDTC) frequently relapse. BRAF and TERT mutations have been extensively related to prognosis in thyroid cancer. In this study, the methylation levels of selected CpGs (5-cytosine-phosphate-guanine-3) comprising a classifier, previously reported by our group, were assessed in combination with BRAF and TERT mutations. We evaluated 121 WDTC, three poorly-differentiated/anaplastic thyroid carcinomas (PDTC/ATC), 22 benign thyroid lesions (BTL), and 13 non-neoplastic thyroid (NT) tissues. BRAF (V600E) and TERT promoter (C228T and C250T) mutations were tested by pyrosequencing and Sanger sequencing, respectively. Three CpGs mapped in PFKFB2, ATP6V0C, and CXXC5 were evaluated by bisulfite pyrosequencing. ATP6V0C hypermethylation and PFKFB2 hypomethylation were detected in poor-prognosis (PDTC/ATC and relapsed WDTC) compared with good-prognosis (no relapsed WDTC) and non-malignant cases (NT/BTL). CXXC5 was hypomethylated in both poor and good-prognosis cases. Shorter disease-free survival was observed in WDTC patients presenting lower PFKFB2 methylation levels (p = 0.004). No association was observed on comparing BRAF (60.7%) and TERT (3.4%) mutations and prognosis. Lower PFKFB2 methylation levels was an independent factor of high relapse risk (Hazard Ratio = 3.2; CI95% = 1.1⁻9.5). PFKFB2 promoter methylation analysis has potential applicability to better stratify WDTC patients according to the recurrence risk, independently of BRAF and TERT mutations.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ATP6V0CHumanthyroid gland carcinoma disease_progressionIDA DNA:hypermethylation:promoterRGD 
Atp6v0cRatthyroid gland carcinoma disease_progressionISOATP6V0C (Homo sapiens)DNA:hypermethylation:promoterRGD 
Atp6v0cMousethyroid gland carcinoma disease_progressionISOATP6V0C (Homo sapiens)DNA:hypermethylation:promoterRGD 

Objects Annotated

Genes (Rattus norvegicus)
Atp6v0c  (ATPase H+ transporting V0 subunit C)

Genes (Mus musculus)
Atp6v0c  (ATPase, H+ transporting, lysosomal V0 subunit C)

Genes (Homo sapiens)
ATP6V0C  (ATPase H+ transporting V0 subunit c)


Additional Information