Association of <i>BRAF<sup>V600E</sup></i> Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers

Han, Peijin; Kim, Hyun‐Seok; Cho, Soonweng; Fazeli, Roghayeh; Najafian, Alireza; Khawaja, Hunain; McAlexander, Melissa A.; Dy, Benzon M.; Sorensen, Meredith J.; Aronova, Anna; Sebo, Thomas J.; Giordano, Thomas J.; Fahey, Thomas J.; Thompson, Geoffrey B.; Gauger, Paul G.; Somervell, Helina; Bishop, Justin A.; Eshleman, James R.; Schneider, Eric B.; Witwer, Kenneth W.; Umbricht, Christopher B.; Zeiger, Martha A.

doi:10.1089/thy.2015.0378

Cited by 54 publications

(36 citation statements)

References 59 publications

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“…A prospective study was performed to show that miR-146b-5p and miR-222 were significantly associated with central lymph node metastases in PTC, indicating that they were the independent predictors of PTC prognosis. 28 In the present study, we mined the TCGA data to obtain PTC-specific lncRNAs for predicting the patients’ survival.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature

You¹,

Yang²,

Sui³

et al. 2018

CMAR

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PurposePapillary thyroid carcinoma (PTC), the most frequent type of malignant thyroid tumor, lacks novel and reliable biomarkers of patients’ prognosis. In the current study, we mined The Cancer Genome Atlas (TCGA) to develop lncRNA signature of PTC.Patients and methodsThe intersection of PTC lncRNAs was obtained from the TCGA database using integrative computational method. By the univariate and multivariate Cox analysis, key lncRNAs were identified to construct the prognostic model. Then, all patients were divided into the high-risk group and low-risk group to perform the Kaplan–Meier (K–M) survival curves and time-dependent receiver operating characteristic (ROC) curve, estimating the prognostic power of the prognostic model. Functional enrichment analysis was also performed. Finally, we verified the results of the TCGA analysis by the Gene Expression Omnibus (GEO) databases and quantitative real-time PCR (qRT-PCR).ResultsAfter the comprehensive analysis, a three-lncRNA signature (PRSS3P2, KRTAP5-AS1 and PWAR5) was obtained. Interestingly, patients with low-risk scores tended to gain obviously longer survival time, and the area under the time-dependent ROC curve was 0.739. Furthermore, gene ontology (GO) and pathway analysis revealed the tumorigenic and prognostic function of the three lncRNAs. We also found three potential transcription factors to help understand the mechanisms of the PTC-specific lncRNAs. Finally, the GEO databases and qRT-PCR validation were consistent with our TCGA bioinformatics results.ConclusionWe built a three-lncRNA signature by mining the TCGA database, which could effectively predict the prognosis of PTC.

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Section: Discussionmentioning

confidence: 99%

Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature

You¹,

Yang²,

Sui³

et al. 2018

CMAR

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“…Furthermore, in patients undergoing prophylactic central neck lymph node dissections, miR-146b is identified as potential markers of central neck lymph node metastasis [50]. Thus, the status of miR-146b expression appears to have supplementary diagnostic value and provides more comprehensive information regarding patient’s condition before surgical intervention.…”

Section: Clinical Applications Of Microrna-146b In Ptcmentioning

confidence: 99%

MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer

Chou

Liu

Kang

2017

IJMS

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Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF linear molecular signaling cascade is known to mediate PTC pathogenesis. However, whether presence of BRAF mutation, the most common genetic alteration in PTC, can affect PTC behavior and prognosis is controversial. MicroRNAs (miRNAs) have been labeled as promising molecular prognostic markers in several tumor types. Our recent studies demonstrated that microRNA-146b (miR-146b) deregulation is associated with PTC aggressiveness and prognosis. Here we summarize the current knowledge related to the functional roles, regulated target genes, and clinical applications of miR-146b in PTC and discuss how these studies provide insights into the key role of miR-146b as an oncogenic regulator promoting cellular transformation as well as a prognosis marker for tumor recurrence in PTC. In conjunction with the current perspectives on miRNAs in a wide variety of human cancers, this review will hopefully translate these updated findings on miR-146b into more comprehensive diagnostic or prognostic information regarding treatment in PTC patients before surgical intervention and follow up strategies.

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“…The study conducted by The Cancer Genome Atlas regarding the classification of PTC showed that miRNA expression is associated with the PTC phenotypes and plays an important role in the prognosis of PTC ( 30 ). Although definitive studies are still limited, miRNA clearly has the potential as an indicator of prognosis in PTC patients ( 60 ). In another study conducted by Cahill et al, which compared a PTC cell line with BRAF mutation and a normal thyroid cell line, the analysis revealed 15 highly expressed and 23 downregulated miRNAs ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Characterization of MicroRNA and mRNA Transcriptome in Papillary Thyroid Carcinoma

et al. 2018

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The incidence rate of papillary thyroid carcinoma (PTC) has rapidly increased in the recent decades, and the microRNA (miRNA) is one of the potential biomarkers in this cancer. Despite good prognosis, certain features such as lymph node metastasis (LNM) and BRAF V600E mutation are associated with a poor outcome. More than 50% of PTC patients present with LNM and BRAF V600E is the most common mutation identified in this cancer. The molecular mechanisms underlying these features are yet to be elucidated. This study aims to elucidate miRNA–genes interaction networks in PTC with or without LNM and to determine the association of BRAF V600E mutation with miRNAs and genes expression profiles. Next generation sequencing was performed to characterize miRNA and gene expression profiles in 20 fresh frozen tumor and the normal adjacent tissues of PTC with LNM positive (PTC LNM-P) and PTC without LNM (PTC LNN). BRAF V600E was genotyped using Sanger sequencing. Bioinformatics integration and pathway analysis were performed to determine the regulatory networks involved. Based on network analysis, we then investigated the association between miRNA and gene biomarkers, and pathway enrichment analysis was performed to study the role of candidate biomarkers. We identified 138 and 43 significantly deregulated miRNAs (adjusted p value < 0.05; log2 fold change ≤ −1.0 or ≥1.0) in PTC LNM-P and PTC LNN compared to adjacent normal tissues, respectively. Ninety-six miRNAs had significant expression ratios of 3p-to-5p in PTC LNM-P as compared to PTC LNN. In addition, ribosomal RNA-reduced RNA sequencing analysis revealed 699 significantly deregulated genes in PTC LNM-P versus normal adjacent tissues, 1,362 genes in PTC LNN versus normal adjacent tissue, and 1,576 genes in PTC LNM-P versus PTC LNN. We provide the evidence of miRNA and gene interactions, which are involved in LNM of papillary thyroid cancer. These findings may lead to better understanding of carcinogenesis and metastasis processes. This study also complements the existing knowledge about deregulated miRNAs in papillary thyroid carcinoma development.

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Association of BRAF^V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers

Cited by 54 publications

References 59 publications

Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature

Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature

MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer

Integrated Characterization of MicroRNA and mRNA Transcriptome in Papillary Thyroid Carcinoma

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Association of BRAFV600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers

Cited by 54 publications

References 59 publications

Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature

Molecular characterization of papillary thyroid carcinoma: a potential three-lncRNA prognostic signature

MicroRNA-146b: A Novel Biomarker and Therapeutic Target for Human Papillary Thyroid Cancer

Integrated Characterization of MicroRNA and mRNA Transcriptome in Papillary Thyroid Carcinoma

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Association of BRAF^V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers