scholarly journals CD73 Overexpression Promotes Progression and Recurrence of Papillary Thyroid Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3042 ◽  
Author(s):  
Young Mun Jeong ◽  
Haejin Cho ◽  
Tae-Min Kim ◽  
Yourha Kim ◽  
Sora Jeon ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
High Expression ◽  
Migration And Invasion ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Tumor Immune Escape ◽  
Free Survival ◽  
Mesenchymal Transition ◽  
Cd73 Expression

CD73 is involved in tumor immune escape and promotes the growth and progression of cancer cells. The functional role of CD73 expression in papillary thyroid carcinoma (PTC) has not yet been established. In 511 patients with PTC, immunohistochemistry for CD73 on tissue microarrays showed that the high expression of CD73 was associated with an aggressive histologic variant (p = 0.002), extrathyroidal extension (p < 0.001), lymph node metastasis (p < 0.001), and BRAFV600E mutation (p = 0.015). Survival analysis results showed that patients with high CD73 expression had worse recurrence-free survival (p = 0.023). CD73 inhibitors induced G1 cell cycle arrest and apoptosis, inhibited the migration and invasion of PTC cells, and suppressed tumor growth in PTC xenograft nude mice. High expression of CD73 (NT5E) mRNA was associated with unfavorable clinicopathologic characteristics, the abundance of Tregs and dendritic cells, depletion of natural killer (NK) cells, and high expression of immune checkpoint genes and epithelial-to-mesenchymal transition-related genes in The Cancer Genome Atlas (TCGA) dataset. Taken together, CD73 expression promotes tumor progression and predicts low recurrence-free survival. Targeting the CD73–adenosine axis in the tumor microenvironment offers an attractive pathway for therapeutic strategies aimed at advanced PTC.

Abstract LBA042: Male Sex is an Independent Predictor of Recurrence-Free Survival in Middle Eastern Papillary Thyroid Carcinoma

2021 ◽  
Author(s):  
KHAWLA S. AL-KURAYA ◽  
Sandeep Kumar Parvathareddy ◽  
Abdul K Siraj ◽  
Felisa De Vera ◽  
Padmanaban Annaiyappanaidu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Independent Predictor ◽  
Middle Eastern ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Male Sex

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

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.

scholarly journals Tumor Mutation Burden Predicts Relapse in Papillary Thyroid Carcinoma With Changes in Genes and Immune Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengli Guo ◽  
Zhen Chen ◽  
Yayi Li ◽  
Sijin Li ◽  
Fei Shen ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Predictor Variable ◽  
Gene Set Enrichment Analysis ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Immune Microenvironment ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
Mutation Burden

BackgroundThe risk factors of papillary thyroid carcinoma (PTC) recurrence are meaningful for patients and clinicians. Tumor mutation burden (TMB) has been a biomarker for the effectiveness of immune checkpoint inhibitor (ICI) and prognosis in cancer. However, the role of TMB and its latent significance with immune cell infiltration in PTC are still unclear. Herein, we aimed to explore the effect of TMB on PTC prognosis.Material and MethodsRNA-seq and DNA-seq datasets of PTC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The Gene Ontology (GO) and gene set enrichment analysis (GSEA 4.0.1) were applied further to explore potential differences in PTC patients’ biological functions. The differentially expressed genes (DEGs) and immune microenvironment between the high and low TMB groups were determined.ResultsTMB had the highest AUC score than other clinical indicators in ROC analysis on recurrence-free survival, and a higher TMB score was related to a worse prognosis. Further, GSEA showed a higher level of oxidative phosphorylation (OXPHOS) in the high TMB group, and four genes correlated with recurrence-free survival rate were identified. The abundance of CD8+ T cells and M1 macrophages in the high TMB group was significantly lower than that in the low TMB group.ConclusionsOur study found that TMB was a better predictor variable at evaluating the risk of PTC recurrence. Moreover, TMB-related genes conferred dramatically correlated prognosis, which was worth exploring in guiding postoperative follow-up and predicting recurrence for PTC patients.

scholarly journals Correlates of Recurrence-Free Survival in Papillary Thyroid Carcinoma: A Cohort Study in an Iranian Population

2021 ◽  
Vol 25 (4) ◽  
pp. 351-360
Author(s):  
Bahareh SHATERI AMIRI ◽  
Mahboobeh HEMMATABADI ◽  
Soghra RABIZADEH ◽  
Hamideh HASANNEJAD ◽  
Alireza ESTEGHAMATI ◽  
...  
Keyword(s):  
Cohort Study ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Iranian Population ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Free Survival

scholarly journals Snail-1 Overexpression Correlates with Metastatic Phenotype in BRAFV600E Positive Papillary Thyroid Carcinoma

2020 ◽  
Vol 9 (9) ◽  
pp. 2701
Author(s):  
Katarzyna Wieczorek-Szukala ◽  
Janusz Kopczynski ◽  
Aldona Kowalska ◽  
Andrzej Lewinski
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Migration And Invasion ◽  
Malignant Neoplasms ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Metastatic Phenotype ◽  
Mutation Status ◽  
Mesenchymal Transition

The ability of cancer to metastasize is regulated by various signaling pathways, including transforming growth factor β (TGFβ), also implicated in the upregulation of Snail-1 transcription factor in malignant neoplasms. B-type Raf kinase gene (BRAF)V600E, the most common driving mutation in papillary thyroid carcinoma (PTC), induces epithelial to mesenchymal transition (EMT) in thyroid cancer cells through changes in the Snail-1 level, increasing cell migration and invasion. However, little is known about the mechanism of Snail-1 and BRAFV600E relations in humans. Our study included 61 PTC patients with evaluated BRAFV600E mutation status. A total of 18 of those patients had lymph node metastases—of whom 10 were BRAFV600E positive, and 8 negative. Our findings indicate that the expression of Snail-1, but not TGFβ1, correlates with the metastatic phenotype in PTC. This is the first piece of evidence that the upregulation of Snail-1 corresponds with the presence of BRAFV600E mutation and increased expression of Snail-1 in metastatic PTC samples is dependent on BRAFV600E mutation status.

Extensive surgery improves recurrence-free survival for children and young patients with class I papillary thyroid carcinoma

1999 ◽  
Vol 34 (12) ◽  
pp. 1799-1804 ◽  
Author(s):  
Catherine A Welch Dinauer ◽  
R.Michael Tuttle ◽  
Daniel K Robie ◽  
Donald R McClellan ◽  
Gary L Francis
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Young Patients ◽  
Class I ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Extensive Surgery

scholarly journals Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma

2017 ◽  
Vol 132 (1) ◽  
pp. 8-13 ◽  
Author(s):  
J Mansour ◽  
D Sagiv ◽  
E Alon ◽  
Y Talmi
Keyword(s):  
Lymph Node ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Prognostic Value ◽  
Lymph Node Ratio ◽  
Regional Recurrence ◽  
Recurrence Free Survival ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Node Ratio

AbstractObjective:Cervical metastases in papillary thyroid carcinoma are associated with increased recurrence. However, their effect on survival remains controversial. This study evaluated literature on the prognostic value of lymph node ratio for loco-regional recurrence and survival in metastatic papillary thyroid carcinoma.Methods:The PubMed database was systematically searched using the terms ‘papillary thyroid carcinoma’ and ‘lymph node ratio’. Articles addressing the association between lymph node ratio and loco-regional recurrence or survival were identified.Results:Nine retrospective studies were included, comprising 12 400 post-thyroidectomy and neck dissection papillary thyroid carcinoma patients (median age, 48.6 years; 76 per cent females). Lymph node ratio was associated with worse recurrence-free survival in 60 and 75 per cent of studies investigating the effect of central compartment metastases and both central and lateral compartment metastases on recurrence-free survival, respectively. One large population-based study showed an association between lymph node ratio and disease-specific mortality in N1nodal disease, but failed to maintain the same association when N1bpatients were excluded.Conclusion:Regional lymph node ratio is an independent predictor for loco-regional recurrence in pathologically staged N1patients with papillary thyroid carcinoma. Patients with a high lymph node ratio should be closely followed up.

scholarly journals MiR-613 inhibits the proliferation, migration, and invasion of papillary thyroid carcinoma cells by directly targeting TAGLN2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yonglian Huang ◽  
Hengwei Zhang ◽  
Lidong Wang ◽  
Chenxi Liu ◽  
Mingyue Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Mesenchymal Transition ◽  
Normal Tissues

Abstract Background Papillary thyroid carcinoma (PTC), with a rapidly increasing incidence, is the most prevalent malignant cancer of the thyroid. However, its pathogenesis is unclear and its specific clinical indicators have not yet been identified. There is increasing evidence that microRNAs (miRNAs) play important roles in tumor occurrence and progression. Specifically, miR-613 participates in the regulation of tumor development in various cancers; however, its effects and mechanisms of action in PTC are still unclear. Therefore, in this study, we investigated the expression and function of miR-613 in PTC. Methods qRT-PCR was used to determine miR-613 expression in 107 pairs of PTC and adjacent-normal tissues as well as in PTC cell lines and to detect TAGLN2 mRNA expression in PTC tissues and adjacent normal tissues. Western blot analysis was performed to identify TAGLN2 and epithelial–mesenchymal transition (EMT) biomarkers. The effects of miR-613 on PTC progression were evaluated by performing MTS, wound-healing, and Transwell assays in vitro. Luciferase reporter assays were also performed to validate the target of miR-613. Results In PTC, miR-613 was significantly downregulated and its low expression level was associated with cervical lymph node metastasis. However, its overexpression significantly suppressed PTC cell proliferation, migration, and invasion and inhibited EMT. TAGLN2 was identified as a target of miR-613, which also significantly inhibited the expression of TAGLN2. Further, the restoration of TAGLN2 expression attenuated the inhibitory effects of miR-613 on PTC cell proliferation and metastasis. Conclusion Our findings demonstrated that miR-613 can suppress the progression of PTC cells by targeting TAGLN2, indicating that miR-613 plays the role of a tumor suppressor in PTC. Overall, these results suggest that the upregulation of miR-613 is a promising therapeutic strategy for PTC.

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