Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data

Chai, Young Jun; Yi, Jin Wook; Jee, Hyeon Gun; Kim, Young A; Kim, Ju Han; Xing, Mingzhao; Lee, Kyu Eun

doi:10.1371/journal.pone.0159235

Cited by 14 publications

(10 citation statements)

References 47 publications

(55 reference statements)

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“…Increased proliferation and cyclin activity are also hallmarks of cancer cells ( Chai et al., 2016a ), thus we aimed to characterize the expression of genes that have previously been shown to be up- or downregulated in thyroid cancer ( Agrawal et al., 2014 ; Chai et al., 2016b ; Costa et al., 2015 ; Wang et al., 2017 ). Interestingly, 72% of genes described as upregulated in thyroid cancer were downregulated in early passage (passage 0–2) organoids compared with primary tissue-derived cells, while some of these genes displayed further downregulation in later passage (passage 3–4) organoids ( Figure 4 A, Table S3 ).…”

Section: Resultsmentioning

confidence: 99%

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

et al. 2021

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Total thyroidectomy as part of thyroid cancer treatment results in hypothyroidism requiring lifelong daily thyroid hormone replacement. Unbalanced hormone levels result in persistent complaints such as fatigue, constipation, and weight increase. Therefore, we aimed to investigate a patient-derived thyroid organoid model with the potential to regenerate the thyroid gland. Murine and human thyroidderived cells were cultured as organoids capable of self-renewal and which expressed proliferation and putative stem cell and thyroid characteristics, without a change in the expression of thyroid tumor-related genes. These organoids formed thyroid-tissue-resembling structures in culture. (Xeno-)transplantation of 600,000 dispersed organoid cells underneath the kidney capsule of a hypothyroid mouse model resulted in the generation of hormone-producing thyroid-resembling follicles. This study provides evidence that thyroid-lineagespecific cells can form organoids that are able to self-renew and differentiate into functional thyroid tissue. Subsequent (xeno-)transplantation of these thyroid organoids demonstrates a proof of principle for functional miniature gland formation.

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Section: Resultsmentioning

confidence: 99%

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

et al. 2021

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“…The high expression of MC in thyroid carcinoma appears to be a good marker for thyroid papillary carcinoma. BRAF somatic mutations, was the most extensively investigated molecular markers and common genetic alterations in PTC [ 51 ]. Many studies have found that higher expression of Braf mutant protein can predict aggressive tumor behavior in PTC, and BRAF V600E IHC has high practical value for the detection of the BRAF V600E mutation in primary and metastatic PTC [ 52 – 53 ].…”

Section: Discussionmentioning

confidence: 99%

A potential biomarker hsa-miR-200a-5p distinguishing between benign thyroid tumors with papillary hyperplasia and papillary thyroid carcinoma

Wang

Huang

et al. 2018

PLoS ONE

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Papillary thyroid carcinoma (PTC) is the most common endocrine cancer with a significantly increase of the incidence recently. Several cytokines, such as thyroid peroxidase (TPO), cluster of differentiation 56 (CD56), Galectin-3, mesothelial cell (MC), cytokeratin 19 (CK19) and BRAF (B-raf) were recommended to be tested by immunohistochemistry (IHC) for a definitive diagnosis, but were still limited in clinical use because of their relative lower sensitivity and specificity. MicroRNA (miRNA), as a new molecular biomarkers, however, has not been reported yet so far. To address this, hsa-miR-200a-5p, a miRNA, was selected and detected in PTC patients by in situ hybrization with benign thyroid tumor with papillary hyperplasia as a control, and the differential expression of hsa-miR-200a-5p between fresh PTC tissues and control was detected by qRT-PCR. Expressive levels of cytokines of TPO, CD56, Galectin-3, MC, CK19 and B-raf were also detected by immunohistochemistry. The correlation was analyzed by SPSS software using Spearman methods. As expected, the hsa-miR-200a-5p expressive level was significantly increased in PTC patients, compared to that of control, and was consistent with that of TPO, CD56, Galectin-3, MC, CK19 and B-raf. In addition, expression of hsa-miR-200a-5p showed negative correlation to that of TPO (rs = - 0.734; **: P < 0.01) and CD56 (rs = - 0.570; **: P < 0.01), but positive correlation to that of Galectin-3 (rs = 0.601; **: P < 0.01), MC (rs = 0.508; **: P < 0.01), CK19 (rs = 0.712; **: P < 0.01) and B-raf (rs = 0.378; **: P < 0.01). PTC and papillary benign thyroid papillary hyperplasia are difficult to distinguish in morphology, so requiring immunohistochemistry to further differentiate the diagnosis, however, for the existing clinical common diagnostic marker for immunohistochemistry, the sensitivity and accuracy are low, it is easy to miss diagnosis. Therefore, there is an urgent need for a rapid and sensitive molecular marker. So miR-200a-5p can be used to assist in the diagnosis of PTC at the molecular level, and as a biomarker, can be effectively used to distinguish between PTC and benign thyroid tumor with papillary hyperplasia.

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“…Despite the fact it is suggested that an overexpression of BRAF may contribute to an activation of the MAPK pathway,silencing of BRAF may induce a regression of melanoma xenografts in vivo . Furthermore, higher BRAF mRNA levels are associated with tumour malignancy regardless of possible mutations in this gene . Interestingly, feline ocular melanomas seem to result in a downregulation of BRAF , however, typical mutations found in human melanomas are not present in feline uveal melanomas.…”

Section: Discussionmentioning

confidence: 99%

Mutation analysis and gene expression profiling of ocular melanomas in cats

Rushton

Ertl²,

Klein³

et al. 2017

Vet Comparative Oncology

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Feline ocular melanomas show a high malignant behaviour, but adjunctive therapies are non-existent. The aim of this pilot study was to determine, whether feline ocular melanomas harbour mutations comparable to mutations in human melanomas and to evaluate the gene expression status of genes known to be involved in initiation and progression of human melanomas. Mutation hotspot regions of several genes of feline ocular melanomas were analysed by DNA sequencing and RNA expression levels of the respective genes and others were evaluated by quantitative real-time polymerase chain reaction (RT-qPCR). Common mutations found in human melanomas are not present in feline tumours. Gene expression analysis revealed a significant upregulation of KIT and LTA4H, as well as a downregulation of GNAQ, GNA11, BRAF and RASSF1 in feline ocular melanomas. As KIT seems to harbour a potential as target gene in human uveal melanomas, future studies should further investigate the potential of KIT as target for adjunctive therapy in feline ocular melanomas.

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Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data

Cited by 14 publications

References 47 publications

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

Generation and Differentiation of Adult Tissue-Derived Human Thyroid Organoids

A potential biomarker hsa-miR-200a-5p distinguishing between benign thyroid tumors with papillary hyperplasia and papillary thyroid carcinoma

Mutation analysis and gene expression profiling of ocular melanomas in cats

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