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

Barros-Filho, Mateus Camargo; Lima, Larissa Barreto Menezes de; Reis, Mariana Bisarro dos; Mello, Julia Bette Homem de; Beltrami, Caroline Moraes; Pinto, Clóvis Antônio Lopes; Kowalski, Luiz Paulo; Rogatto, Sílvia Regina

doi:10.3390/ijms20061334

Cited by 10 publications

(8 citation statements)

References 35 publications

(61 reference statements)

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“…Point mutations in BRAF (codon 600), KRAS (codon 12/13), HRAS (codon 61), and KRAS (codon 61) were evaluated by pyrosequencing and RET rearrangements (RET/PTC1 and RET/PTC3) by RT-qPCR, as previously described (27). TERT promoter mutations (C228T and C250T hotspots) were investigated by direct Sanger sequencing, as described elsewhere (28).…”

Section: Detection Of Genomic Alterationsmentioning

confidence: 99%

GADD45B Transcript Is a Prognostic Marker in Papillary Thyroid Carcinoma Patients Treated With Total Thyroidectomy and Radioiodine Therapy

et al. 2020

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Currently, there is a lack of efficient recurrence prediction methods for papillary thyroid carcinoma (PTC). In this study, we enrolled 202 PTC patients submitted to total thyroidectomy and radioiodine therapy with long-term follow-up (median = 10.7 years). The patients were classified as having favorable clinical outcome (PTC-FCO, no disease in the follow-up) or recurrence (PTC-RE). Alterations in BRAF, RAS, RET, and TERT were investigated (n = 202) and the transcriptome of 48 PTC (>10 years of follow-up) samples was profiled. Although no mutation was associated with the recurrence risk, 68 genes were found as differentially expressed in PTC-RE compared to PTC-FCO. Pathway analysis highlighted a potential role of cancer-related pathways, including signal transduction and FoxO signaling. Among the eight selected genes evaluated by RT-qPCR, SLC2A4 and GADD45B showed down-expression exclusively in the PTC-FCO group compared to non-neoplastic tissues (NT). Increased expression of GADD45B was an independent marker of shorter disease-free survival [hazard ratio (HR) 2.9; 95% confidence interval (CI95) 1.2-7.0] in our cohort and with overall survival in the TCGA dataset (HR = 4.38, CI95 1.2-15.5). In conclusion, GADD45B transcript was identified as a novel prognostic marker candidate in PTC patients treated with total thyroidectomy and radioiodine therapy.

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Section: Detection Of Genomic Alterationsmentioning

confidence: 99%

GADD45B Transcript Is a Prognostic Marker in Papillary Thyroid Carcinoma Patients Treated With Total Thyroidectomy and Radioiodine Therapy

et al. 2020

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“…The effect of methylation alterations in thyroid carcinogenesis is demonstrated by downregulation of several tumor suppressors thyroid cancer cells, such as; TSHR, PTEN, RASSF1A, CDKN2A, DAPK1, TIMP3, ECAD, and RAP1GAP [193][194][195][196][197][198]. On the other hand, MAP17, CXCL12, HORMAD2, and PFKFB2 are hypomethylated and upregulated in aggressive thyroid cancer [199][200][201][202].…”

Section: Epigenetic Changes In Thyroid Cancermentioning

confidence: 99%

Multi-omics Signatures and Translational Potential to Improve Thyroid Cancer Patient Outcome

Boufraqech

Nilubol

2019

Cancers

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Recent advances in high-throughput molecular and multi-omics technologies have improved our understanding of the molecular changes associated with thyroid cancer initiation and progression. The translation into clinical use based on molecular profiling of thyroid tumors has allowed a significant improvement in patient risk stratification and in the identification of targeted therapies, and thereby better personalized disease management and outcome. This review compiles the following: (1) the major molecular alterations of the genome, epigenome, transcriptome, proteome, and metabolome found in all subtypes of thyroid cancer, thus demonstrating the complexity of these tumors and (2) the great translational potential of multi-omics studies to improve patient outcome.

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“…Genome-wide studies performed in different tumor types revealed methylome signatures able to stratify cancer subtypes [24], predict cancer outcomes [25][26][27][28], and identify epigenetic events related to inherent and acquired chemotherapy resistance [29]. Differential DNA methylation of specific CpG sites has contributed to the understanding of radiotherapy response with or without chemotherapy in a variety of cancer types, including glioblastoma, breast, gastric and colorectal cancers [30].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer

Canto

Barros-Filho

Rainho

et al. 2020

Cancers

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The treatment for locally advanced rectal carcinomas (LARC) is based on neoadjuvant chemoradiotherapy (nCRT) and surgery, which results in pathological complete response (pCR) in up to 30% of patients. Since epigenetic changes may influence response to therapy, we aimed to identify DNA methylation markers predictive of pCR in LARC patients treated with nCRT. We used high-throughput DNA methylation analysis of 32 treatment-naïve LARC biopsies and five normal rectal tissues to explore the predictive value of differentially methylated (DM) CpGs. External validation was carried out with The Cancer Genome Atlas-Rectal Adenocarcinoma (TCGA-READ 99 cases). A classifier based on three-CpGs DM (linked to OBSL1, GPR1, and INSIG1 genes) was able to discriminate pCR from incomplete responders with high sensitivity and specificity. The methylation levels of the selected CpGs confirmed the predictive value of our classifier in 77 LARCs evaluated by bisulfite pyrosequencing. Evaluation of external datasets (TCGA-READ, GSE81006, GSE75546, and GSE39958) reproduced our results. As the three CpGs were mapped near to regulatory elements, we performed an integrative analysis in regions associated with predicted cis-regulatory elements. A positive and inverse correlation between DNA methylation and gene expression was found in two CpGs. We propose a novel predictive tool based on three CpGs potentially useful for pretreatment screening of LARC patients and guide the selection of treatment modality.

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

Cited by 10 publications

References 35 publications

GADD45B Transcript Is a Prognostic Marker in Papillary Thyroid Carcinoma Patients Treated With Total Thyroidectomy and Radioiodine Therapy

GADD45B Transcript Is a Prognostic Marker in Papillary Thyroid Carcinoma Patients Treated With Total Thyroidectomy and Radioiodine Therapy

Multi-omics Signatures and Translational Potential to Improve Thyroid Cancer Patient Outcome

Comprehensive Analysis of DNA Methylation and Prediction of Response to NeoadjuvantTherapy in Locally Advanced Rectal Cancer

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