The long and still uncertain journey of BRAF as a prognostic tool in patients with papillary thyroid cancer

Scheffel, Rafael Selbach; Maia, Ana Luiza

doi:10.20945/2359-3997000000140

Cited by 4 publications

(5 citation statements)

References 9 publications

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“…Tumors classified as BRAF V600E-like have increased heterogeneity, are less differentiated, demonstrate high levels of MAPK signaling, and are enriched for classical and tall cell histologic subtypes of PTC [5]. Despite these interesting findings, subsequent studies evaluating the impact of the BRAF V600E mutation on clinical outcomes (persistent disease, recurrence, and survival) have shown conflicting results [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

BRAF mutations in thyroid cancer

Scheffel

Dora

Maia

2021

Current Opinion in Oncology

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Purpose of reviewActivating mutations in the mitogen-activated protein kinase (MAPK) pathway play an important role in papillary (PTC) and anaplastic (ATC) thyroid cancer. The aim of this review is to discuss the impact of BRAF mutations on clinical features and treatment of patients with thyroid cancer. Recent findingsDespite the unfavorable course associated with PTCs harboring BRAF V600E mutation, its prognostic role remains debated. BRAF V600E-driven tumors exhibit high Extracellular signal-regulated kinase phosphorylation, leading to unregulated cell proliferation and inhibition of the required genes for radioiodine responsiveness in thyroid cancer. The mechanism associated with the variable BRAF-mutant tumor aggressiveness remains unclear and other pathways are likely to co-operate to promote cancer progression. Overexpression of the Notch signaling and loss of individual switch/ sucrose non-fermentable chromatin-remodeling complexes subunits might be involved. The combination of the BRAF inhibitor dabrafenib and the mitogen-activated protein kinase kinase inhibitor trametinib has shown remarkable results in clinical trials of patients with BRAF-mutated ATCs.

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Section: Introductionmentioning

confidence: 99%

BRAF mutations in thyroid cancer

Scheffel

Dora

Maia

2021

Current Opinion in Oncology

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“…From the clinical perspective view, the prognostic role of BRAF V600E mutation is still controversial (5).…”

Section: Introductionmentioning

confidence: 99%

“…From the clinical perspective view, the prognostic role of BRAF V600E mutation is still controversial ( 5 ). Several studies were focused on searching for an association between BRAF V600E mutation and features related to unfavorable course of the disease and showed conflicting results ( 6 – 8 ).…”

Section: Introductionmentioning

confidence: 99%

The BRAFV600E mutation analysis and risk stratification in papillary thyroid carcinoma

Scheffel¹,

Cristo²,

Romitti³

et al. 2020

Archives of Endocrinology and Metabolism

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Objective: Although the prognostic role of BRAF V600E mutation in papillary thyroid carcinoma (PTC) is controversial, the American Thyroid Association (ATA) includes the mutational status in their risk stratification system. To evaluate the impact of the BRAF V600E mutation status on PTC risk stratification. Subjects and methods: PTC patients attending a university-based hospital who had the analysis of the BRAF V600E mutation were included. Persistent disease was defined as the presence of biochemical or structural disease. The performance of the ATA risk stratification system on predicting persistent disease with or without the BRAF V600E mutation status information was evaluated. Results: Of the 134 patients evaluated, 44 (32.8%) carried BRAF V600E mutation. The median tumor size was 1.7 cm (P25-75 1.0-3.0), 64 (47.8%) patients had lymph node, and 11 (8.2%) distant metastases. According to the ATA risk stratification system, patients were classified as low, intermediate, and high risk in 55 (41%), 59 (44%), and 20 (14%) patients, respectively. The data on BRAF V600E mutation reclassified 12 (8.9%) patients from low to intermediate risk. After a median follow-up of 8.5 years, the prevalence of persistent disease was similar in patients with and without BRAF V600E mutation (P = 0.42). Multivariate analysis failed to demonstrate an association between the BRAF V600E mutation and persistent disease status (RR 0.96; 95%CI 0.47-1.94). Notably, none of the patients reclassified from low to intermediate risk showed persistent disease on follow-up. Conclusion: Inclusion of BRAF V600E mutational status has a limited impact on risk stratification and does not add to the prediction of outcomes in PTC patients.

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“…[ 11 ] Scheffel and Maia reported that the long and still uncertain journey of BRAF functioned as a prognostic signature in patients with TPC. [ 12 ] Liu et al revealed a key prognostic value of a 2-microRNA signature for TPC. [ 13 ] However, few studies have indicated that TFs were independent biomarkers for TPC prognosis.…”

Section: Introductionmentioning

confidence: 99%

“…For example, Luzón-Toro et al demonstrated that lncRNA LUCAT1 served as a novel prognostic biomarker for patients with TPC [11] . Scheffel and Maia reported that the long and still uncertain journey of BRAF functioned as a prognostic signature in patients with TPC [12] . Liu et al revealed a key prognostic value of a 2-microRNA signature for TPC [13] .…”

Section: Introductionmentioning

confidence: 99%

A 6 transcription factors-associated nomogram predicts the recurrence-free survival of thyroid papillary carcinoma

Wang

Tian²,

Xie³

et al. 2021

Medicine

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Various researches demonstrated that transcription factors (TFs) played a crucial role in the progression and prognosis of cancer. However, few studies indicated that TFs were independent biomarkers for the prognosis of thyroid papillary carcinoma (TPC). Our aim was to establish and validate a novel TF signature for the prediction of TPC patients’ recurrence-free survival (RFS) from The Cancer Genome Atlas (TCGA) database to improve the prediction of survival in TPC patients. The genes expression data and corresponding clinical information for TPC were obtained from TCGA database. In total, 722 TFs and 545 TPC patients with eligible clinical information were determined to build a novel TF signature. All TFs were included in a univariate Cox regression model. Then, the least absolute shrinkage and selection operator Cox regression model was employed to identify candidate TFs relevant to TPC patients’ RFS. Finally, multivariate Cox regression was conducted via the candidate TFs for the selection of the TF signatures in the RFS assessment of TPC patients. We identified 6 TFs that were related to TPC patients’ RFS. Receiver operating characteristic analysis was performed in training, validation, and whole datasets, we verified the high capacity of the 6-TF panel for predicting TPC patients’ RFS (AUC at 1, 3, and 5 years were 0.880, 0.934, and 0.868, respectively, in training dataset; 0.760, 0.737, and 0.726, respectively, in validation dataset; and 0.777, 0.776, and 0.761, respectively, in entire dataset). The result of Kaplan–Meier analysis suggested that the TPC patients with low scores had longer RFS than the TPC patients with high score ( P = .003). A similar outcome was displayed in the validation dataset ( P = .001) and the entire dataset ( P = 2e-05). In addition, a nomogram was conducted through risk score, cancer status, C-index, receiver operating characteristic, and the calibration plots analysis implied good value and clinical utility of the nomogram. We constructed and validated a novel 6-TF signature-based nomogram for predicting the RFS of TPC patients.

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The long and still uncertain journey of BRAF as a prognostic tool in patients with papillary thyroid cancer

Cited by 4 publications

References 9 publications

BRAF mutations in thyroid cancer

BRAF mutations in thyroid cancer

The BRAFV600E mutation analysis and risk stratification in papillary thyroid carcinoma

A 6 transcription factors-associated nomogram predicts the recurrence-free survival of thyroid papillary carcinoma

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