Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis

Chai, Young Jun; Kim, Young A; Jee, Hyeon Gun; Yi, Jin Wook; Jang, Bo Gun; Lee, Kyu Eun; Park, Young Joo; Youn, Yeo-Kyu

doi:10.1016/j.surg.2014.08.050

Cited by 4 publications

(3 citation statements)

References 23 publications

(29 reference statements)

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“…Since the start of the TCGA project in 2006, multiplatform genomic data from more than 20 types of carcinomas have been provided through the TCGA data portal, and multiple studies have been performed using this powerful open resource. Several studies of thyroid carcinoma using this data resource have been reported recently [ 14 , 17 , 18 ]. The TCGA portal provides an enormous amount of information, including data regarding microsatellite instability, DNA sequencing, miRNA sequencing, protein expression, mRNA sequencing, DNA methylation, copy number variation, clinical information, and clinical images.…”

Section: Discussionmentioning

confidence: 99%

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

Chai

Jee

et al. 2016

PLoS ONE

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BackgroundBRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC), and it is associated with high-risk prognostic factors. However, the significance of the BRAF mRNA level in PTC remains unknown. We evaluated the significance of BRAF mRNA expression level by analyzing PTC data from The Cancer Genome Atlas (TCGA) database.MethodsData from 499 patients were downloaded from the TCGA database. After excluding other PTC variants, we selected 353 cases of classic PTC, including 193 cases with BRAFV600E and 160 cases with the wild-type BRAF. mRNA abundances were measured using RNA-Seq with the Expectation Maximization algorithm.ResultsThe mean BRAF mRNA level was significantly higher in BRAFV600E patients than in patients with wild-type BRAF (197.6 vs. 179.3, p = 0.031). In wild-type BRAF patients, the mean BRAF mRNA level was higher in cases with a tumor > 2 cm than those with a tumor ≤ 2.0 cm (189.4 vs. 163.8, p = 0.046), and was also higher in cases with lymph node metastasis than in those without lymph node metastasis (188.5 vs. 157.9, p = 0.040). Within BRAFV600E patients, higher BRAF mRNA expression was associated with extrathyroidal extension (186.4 vs. 216.4, p = 0.001) and higher T stage (188.1 vs. 210.2, p = 0.016).ConclusionsA higher BRAF mRNA expression level was associated with tumor aggressiveness in classic PTC regardless of BRAF mutational status. Evaluation of BRAF mRNA level may be helpful in prognostic risk stratification of PTC.

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Section: Discussionmentioning

confidence: 99%

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

Chai

Jee

et al. 2016

PLoS ONE

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“…Still other studies have reported associations with Nodal and neoplasia. In thyroid cancer, Nodal was strongly correlated with papillary and follicular carcinomas while Nodal was detected at higher levels in colon cancer tissue compared to adjacent non-cancerous tissue [105, 160]. …”

Section: Nodal and Cancermentioning

confidence: 99%

Plasticity underlies tumor progression: role of Nodal signaling

Bodenstine

Chandler

Seftor

et al. 2016

Cancer Metastasis Rev

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The transforming growth factor beta (TGFβ) superfamily member Nodal is an established regulator of early embryonic development, with primary roles in endoderm induction, left-right asymmetry and primitive streak formation. Nodal signals through TGFβ family receptors at the plasma membrane and induces signaling cascades leading to diverse transcriptional regulation. While conceptually simple, the regulation of Nodal and its molecular effects are profoundly complex and context dependent. Pioneering work by developmental biologists has characterized the signaling pathways, regulatory components, and provided detailed insight into the mechanisms by which Nodal mediates changes at the cellular and organismal levels. Nodal is also an important factor in maintaining pluripotency of embryonic stem cells through regulation of core transcriptional programs. Collectively, this work has led to an appreciation for Nodal as a powerful morphogen capable of orchestrating multiple cellular phenotypes. Although Nodal is not active in most adult tissues, its re-expression and signaling have been linked to multiple types of human cancer, and Nodal has emerged as a driver of tumor growth and cellular plasticity. In vitro and in vivo experimental evidence has demonstrated that inhibition of Nodal signaling reduces cancer cell aggressive characteristics, while clinical data have established associations with Nodal expression and patient outcomes. As a result, there is great interest in the potential targeting of Nodal activity in a therapeutic setting for cancer patients that may provide new avenues for suppressing tumor growth and metastasis. In this review, we evaluate our current understanding of the complexities of Nodal function in cancer and highlight recent experimental evidence that sheds light on the therapeutic potential of its inhibition.

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“…45 Nodal is an embryonic morphogen 46 whose expression is mostly restricted in embryonic tissues and reproductive cell types, while being undetectable in most normal adult tissues. 47,48 However, recent research studies demonstrate the re-expression of Nodal during cancer progression, including malignant thyroid tumors, 49 hepatocellular carcinomas, 50 pancreatic cancer, 51 melanoma, 52 and carcinomas of the endometrium 53 and prostate. 54 Nodal is synthesized as an inactive precursor form consisting of a single peptide, prodomain, and mature domain.…”

Section: Stemness Of Pancreatic Cancer Cellsmentioning

confidence: 99%

TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment

Mouti

Pauklin

2021

Molecular Therapy

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Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis

Cited by 4 publications

References 23 publications

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

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

Plasticity underlies tumor progression: role of Nodal signaling

TGFB1/INHBA Homodimer/Nodal-SMAD2/3 Signaling Network: A Pivotal Molecular Target in PDAC Treatment

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