Value of Echogenic Foci in Diagnosing Papillary Thyroid Carcinoma and Predicting Aggressive Biological Behavior

ABSTRACTBackgroundThe BRAFV600E mutations is an important molecular event in the occurrence and development of papillary thyroid carcinoma (PTC). A qualitative detection of the BRAFV600E mutation is still insufficient to explain the biological behavior of PTC. Though quantitative detection of the BRAFV600E mutation can reflect certain characteristics of PTC, its clinical value is still controversial. We aimed to investigate the association between the ratio of BRAFV600E alleles and clinicopathological parameters in PTC patients.MethodsGenomic DNA was extracted from specimens obtained from 329 PTC patients undergoing thyroidectomy. The ratio of BRAFV600E alleles was determined by amplification refractory mutation system (ARMS) and droplet digital polymerase chain reaction (ddPCR). Inconsistent results were further verified by next-generation sequencing (NGS). The clinicopathologic features, clinical tumor stage, and tumor recurrence risk stratification of all patients were correlated with the ratio of BRAFV600E alleles.ResultsThe sensitivity of ddPCR was superior to that of ARMS and almost the same as that of NGS. In total, 275 of 329 patients had the BRAFV600E mutation as determined by ARMS, ddPCR and NGS. The ratio of BRAFV600E alleles ranged from 0.17%-48.0%, with a median ratio of 12.58%, and significantly correlated with tumor size (p<0.001), capsule or extrathyroidal invasion (p<0.001), the number or rate of lymph node metastases (p<0.001), tumor stage (p=0.006) and tumor recurrence risk (p<0.001) but not with sex, age or multifocality. The ratio of BRAFV600E alleles was much lower in PTC patients with Hashimoto’s thyroiditis than in those without (p<0.001).ConclusionsThe ratio of BRAFV600E alleles can reliably reflect the biological behavior of PTC, making it a molecular-based stratification index of recurrence risk. The quantitative detection of BRAFV600E has the potential to guide the clinical diagnosis and treatment of PTC.

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Preoperative Ultrasonographic Features of Papillary Thyroid Carcinoma Predict Biological Behavior

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-4072 ◽

2013 ◽

Vol 98 (4) ◽

pp. 1476-1482 ◽

Cited By ~ 43

Author(s):

Sang Yu Nam ◽

Jung Hee Shin ◽

Boo-Kyung Han ◽

Eun Young Ko ◽

Eun Sook Ko ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Biological Behavior ◽

Papillary Thyroid

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Heparanase regulates cell proliferation, apoptosis, migration and invasion of papillary thyroid carcinoma cells with multiple signaling pathways involved

10.21203/rs.3.rs-38766/v1 ◽

2020 ◽

Author(s):

Chuanjia Yang ◽

Siyang Zhang ◽

Xiaoying Chang ◽

Yonglian Huang ◽

Dongxu Cui ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Signaling Pathways ◽

Signaling Molecules ◽

Biological Behavior ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Downstream Signaling ◽

Multiple Signaling

Abstract Background Heparanase (HPSE) is an endo-β-D-glucuronidase, which is found overexpressed in various human cancers. The purpose of our work was to investigate the possible role of HPSE and the involved signaling molecules in the development of papillary thyroid carcinoma (PTC). Methods The expression of HPSE was examined in 80 samples of PTC by immunohistochemistry. In cell studies, the expression plasmid of HPSE and RNA interference with shRNA specific for HPSE were used to elucidate the effects of HPSE on proliferation, apoptosis, migration and invasion in PTC cells of B-CPAP and KTC-1. The probable downstream signaling molecules of HPSE were also explored. Results 75.0% (60 out of 80) of PTC samples was detected high expression of HPSE, which was significantly correlated with tumor size, lymph node metastasis and stage status. In cell studies, the upregulation of HPSE significantly promoted cell proliferation, migration and invasion of B-CPAP and KTC-1 cells, and interfered with cell apoptosis. On the contrary, knockdown of HPSE exhibited the opposite effects. Compared with the parental cells, HPSE silencing cells showed attenuated capabilities of proliferation, migration and invasion, yet the apoptotic rate of transfected cells was increased. The activations of various signaling molecules correlated with cell biological behavior were found to be regulated by HPSE upregulation or knockdown. Conclusions Our results suggested that HPSE probably contributed to the progression and metastasis of PTC, which were associated with multiple signaling pathways. HPSE could be a potent molecular target for the therapeutic strategy of PTC.

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miR-183 regulates biological behavior in papillary thyroid carcinoma by targeting the programmed cell death 4

Oncology Reports ◽

10.3892/or.2015.3971 ◽

2015 ◽

Vol 34 (1) ◽

pp. 211-220 ◽

Cited By ~ 12

Author(s):

CHUANKUI WEI ◽

HONGMING SONG ◽

XIAOGUO SUN ◽

DENGFENG LI ◽

JIALU SONG ◽

...

Keyword(s):

Cell Death ◽

Papillary Thyroid Carcinoma ◽

Programmed Cell Death ◽

Thyroid Carcinoma ◽

Biological Behavior ◽

Papillary Thyroid ◽

Programmed Cell Death 4

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Expression of heparanase regulates cell proliferation, apoptosis, migration and invasion in vitro in papillary thyroid carcinoma cells with multiple signaling pathways involved

10.21203/rs.2.13185/v1 ◽

2019 ◽

Author(s):

Chuanjia Yang ◽

Siyang Zhang ◽

Xiaoying Chang ◽

Yonglian Huang ◽

Dongxu Cui ◽

...

Keyword(s):

Cell Proliferation ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Signaling Pathways ◽

Signaling Molecules ◽

Carcinoma Cells ◽

Biological Behavior ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Multiple Signaling

Abstract Background Heparanase (HPSE) is an endo-β-D-glucuronidase, which is found overexpressed in various human cancers. The purpose of our work was to investigate the possible role of HPSE and the involved signaling molecules in the development of papillary thyroid carcinoma. Methods In this study, the expression plasmid of HPSE and RNA interference with shRNA specific for HPSE were used to elucidate the effects of HPSE on proliferation, apoptosis, migration and invasion in papillary thyroid carcinoma cells of B-CPAP. The probable downstream signaling molecules of HPSE were also explored. Results The results showed that upregulation of HPSE significantly promoted cell proliferation, migration and invasion of B-CPAP cells, and interfered with cell apoptosis. On the contrary, knockdown of HPSE exhibited the opposite effects. Compared with the parental cells, HPSE silencing cells showed attenuated capabilities of proliferation, migration and invasion, yet the apoptotic rate of transfected cells was increased. The activations of various signaling molecules correlated with cell biological behavior were found to be regulated by HPSE upregulation or knockdown. Conclusions Our results suggested that HPSE probably contributed to the progression and metastasis of papillary thyroid carcinoma, which were associated with multiple signaling pathways. HPSE could be a potent molecular target for the therapeutic strategy of papillary thyroid carcinoma.

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Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma

PeerJ ◽

10.7717/peerj.5363 ◽

2018 ◽

Vol 6 ◽

pp. e5363 ◽

Cited By ~ 2

Author(s):

Huihui Ren ◽

Zhelong Liu ◽

Siyue Liu ◽

Xinrong Zhou ◽

Hong Wang ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Expression Profile ◽

Critical Role ◽

Expression Level ◽

Biological Behavior ◽

Receiver Operating Curve ◽

Circular Rnas ◽

Papillary Thyroid ◽

Qrt Pcr

Background Differently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC. Methods We investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs. Results In total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78–0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75–0.96]) for hsa_circRNA_007148. Discussion The study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients.

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LDHA induces EMT gene transcription and regulates autophagy to promote the metastasis and tumorigenesis of papillary thyroid carcinoma

Cell Death and Disease ◽

10.1038/s41419-021-03641-8 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Xiukun Hou ◽

Xianle Shi ◽

Wei Zhang ◽

Dapeng Li ◽

Linfei Hu ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Glucose Metabolism ◽

Thyroid Carcinoma ◽

Therapeutic Target ◽

Metabolic Reprogramming ◽

Biological Behavior ◽

Migration And Invasion ◽

Papillary Thyroid ◽

Mesenchymal Transition ◽

Expression Levels

AbstractPapillary thyroid carcinoma (PTC) is one of the most common kinds of endocrine-related cancer and has a heterogeneous prognosis. Metabolic reprogramming is one of the hallmarks of cancers. Aberrant glucose metabolism is associated with malignant biological behavior. However, the functions and mechanisms of glucose metabolism genes in PTC are not fully understood. Thus, data from The Cancer Genome Atlas database were analyzed, and lactate dehydrogenase A (LDHA) was determined to be a potential novel diagnostic and therapeutic target for PTCs. The research objective was to investigate the expression of LDHA in PTCs and to explore the main functions and relative mechanisms of LDHA in PTCs. Higher expression levels of LDHA were found in PTC tissues than in normal thyroid tissues at both the mRNA and protein levels. Higher expression levels of LDHA were correlated with aggressive clinicopathological features and poor prognosis. Moreover, we found that LDHA not only promoted PTC migration and invasion but also enhanced tumor growth both in vitro and in vivo. In addition, we revealed that the metabolic products of LDHA catalyzed induced the epithelial–mesenchymal transition process by increasing the relative gene H3K27 acetylation. Moreover, LDHA knockdown activated the AMPK pathway and induced protective autophagy. An autophagy inhibitor significantly enhanced the antitumor effect of FX11. These results suggested that LDHA enhanced the cell metastasis and proliferation of PTCs and may therefore become a potential therapeutic target for PTCs.

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