scholarly journals Immune landscape of papillary thyroid cancer and immunotherapeutic implications

2018 ◽  
Vol 25 (5) ◽  
pp. 523-531 ◽  
Author(s):  
Kwon Joong Na ◽  
Hongyoon Choi
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Negative Correlation ◽  
Immune Cell ◽  
Immune Escape ◽  
Critical Role ◽  
Significant Negative Correlation ◽  
The Cancer Genome Atlas ◽  
Papillary Thyroid

Although papillary thyroid cancer (PTC) is curable with excellent survival rate, patients with dedifferentiated PTC suffer the recurrence or death. As cancer immune escape plays a critical role in cancer progression, we aimed to investigate the relationship between differentiation and immune landscape of PTC and its implications for immunotherapy. Using The Cancer Genome Atlas data, we estimated the immune cell enrichment scores and overall immune infiltration, ImmuneScore, to characterize the immune landscape of PTC. Thyroid differentiation score (TDS) was calculated from 16 thyroid function genes. We demonstrated that ImmuneScore had a significant negative correlation with TDS, and BRAFV600E+ tumors showed significantly low TDS and high ImmuneScore. Enrichment scores of myeloid cells and B-cells were negatively correlated with TDS, while those of plasma cells were positively correlated with TDS. In addition, the association between TDS, ImmuneScore and immunosuppressive markers (CTLA-4, PD-L1, HLA-G) were evaluated according to BRAFV600E status. All immunosuppressive markers expression had a significant negative correlation with TDS, and they were significantly higher in BRAFV600E+ status. Subgroups were divided by median values of TDS and ImmuneScore, and immunosuppressive markers of these subgroups were compared. The immunosuppressive markers expression was the highest in high ImmuneScore and low TDS subgroup. Furthermore, ImmuneScore had a significant association with recurrence-free survival, irrespective of clinicopathologic factors including BRAFV600E status. These findings based on gene expression data illuminate the immune landscape of PTC and its association with TDS, immunosuppressive markers and recurrence. Our results would be extended to investigate immunotherapeutic approaches in PTC.

scholarly journals Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770534 ◽  
Author(s):  
Jing Sun ◽  
Run Shi ◽  
Sha Zhao ◽  
Xiaona Li ◽  
Shan Lu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Division ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Biological Significance ◽  
Cell Division Cycle ◽  
The Cancer Genome Atlas ◽  
Papillary Thyroid ◽  
Normal Tissues

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

scholarly journals Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression

2014 ◽  
Vol 21 (6) ◽  
pp. 891-902 ◽  
Author(s):  
Min-Hee Kim ◽  
Ja Seong Bae ◽  
Dong-Jun Lim ◽  
Hyoungnam Lee ◽  
So Ra Jeon ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Tumour Size ◽  
External Validation ◽  
Allelic Frequency ◽  
The Cancer Genome Atlas ◽  
Braf V600e ◽  
Validation Dataset ◽  
Papillary Thyroid ◽  
Additional Information

The BRAF V600E mutation is the most common genetic alteration in thyroid cancer. However, its clinicopathological significance and clonal mutation frequency remain unclear. To clarify the inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features of classic papillary thyroid carcinoma (PTC). Tumour tissues from two independent sets of patients with classic PTC were manually microdissected and analysed for the presence or absence of the BRAF mutation and the mutant allelic frequency using quantitative pyrosequencing. For external validation, the Cancer Genome Atlas (TCGA) data were analysed. The BRAF V600E mutation was found in 264 (82.2%) out of 321 classic PTCs in the training set. The presence of BRAF V600E was only associated with extrathyroidal extension and the absence of thyroiditis. In BRAF V600E-positive tumours, the mutant allelic frequency varied from 8 to 41% of the total BRAF alleles (median, 20%) and directly correlated with tumour size and the number of metastatic lymph nodes. Lymph node metastases were more frequent in PTCs with a high (≥20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (P=0.010). These results were reinforced by validation dataset (n=348) analysis but were not reproduced in the TCGA dataset. In a population with prevalent BRAF mutations, quantitative analysis of the BRAF mutation could provide additional information regarding tumour behaviour, which is not reflected by qualitative analysis. Nonetheless, prospective studies are needed before the mutated allele percentage can be considered as a prognostic factor.

LncRNA FOXD2‐AS1 accelerates the papillary thyroid cancer progression through regulating the miR‐485‐5p/KLK7 axis

2018 ◽  
Vol 120 (5) ◽  
pp. 7952-7961 ◽  
Author(s):  
Yayuan Zhang ◽  
Jintao Hu ◽  
Wenbing Zhou ◽  
Hengyuan Gao
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Papillary Thyroid

scholarly journals LncRNA LINC00460 promotes the papillary thyroid cancer progression by regulating the LINC00460/miR-485-5p/Raf1 axis

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Guangjun Li ◽  
Qingli Kong
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Cancer Progression ◽  
Binding Sites ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Papillary Thyroid ◽  
Potential Biomarker ◽  
Common Malignancy

Abstract Background Papillary thyroid cancer (PTC) is the most common malignancy of all thyroid cancers. LncRNA LINC00460 has been proved to play roles in the oncogenesis and progression of various tumors, including papillary thyroid cancer. However, the potential molecular mechanism of LINC00460 in PTC is poorly investigated. Results LINC00460 was upregulated in PTC tissues and cells. Raf1 was upregulated in PTC tissues, but miR-485-5p was down-regulated. High LINC00460 expression was associated with poor prognosis. LINC00460 knockdown suppressed proliferation, migration, invation and EMT of PTC cells. Bioinformatics prediction revealed that LINC00460 had binding sites with miR-485-5p, which was validated by luciferase reporter assay. In addition, miR-485-5p was confirmed to directly target Raf1 3′-UTR. Moreover, LINC00460 promoted PTC progression by sponging miR-485-5p to elevate the expression of Raf1. Knockdown of LINC00460 restrained tumor growth in vivo. Conclusion LINC00460 induced proliferation, migration, invation and EMT of PTC cells by regulating the LINC00460/miR-485-5p/Raf1 axis, which indicated that LINC00460 may be a potential biomarker and therapeutic target for PTC.

scholarly journals Mouse Models of Follicular and Papillary Thyroid Cancer Progression

2012 ◽  
Vol 2 ◽  
Author(s):  
Marika A. Russo ◽  
Valeria G. Antico Arciuch ◽  
Antonio Di Cristofano
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Mouse Models ◽  
Cancer Progression ◽  
Papillary Thyroid

scholarly journals Downregulation of TSPAN13 by miR-369-3p inhibits cell proliferation in papillary thyroid cancer (PTC)

2018 ◽  
Author(s):  
Peng Li ◽  
Mingqiang Dong ◽  
Zhigang Wang
Keyword(s):  
Cell Proliferation ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Expression Profiles ◽  
Surface Proteins ◽  
The Cancer Genome Atlas ◽  
Luciferase Reporter ◽  
Papillary Thyroid ◽  
Small Interfering Rnas

Previous studies demonstrated dysregulation of different microRNAs in thyroid cancer. Tetraspanins (TSPANs) are cell surface proteins with critical roles in many cellular processes, and implications in tumor development. Here we investigated the role of miR-369-3p in papillary thyroid cancer (PTC) and its association with TSPAN13. miR-369-3p and the TSPAN13 gene expression profiles of 513 thyroid cancer and 59 normal thyroid tissues were downloaded from the Cancer Genome Atlas database. Thyroid cancer tissues were classified according to the histological type, grouped based on low and high median miR-369-3p and TSPAN13 expression, and analyzed in relation to overall survival (OS) of patients. Human PTC cell lines (TPC-1 and GLAG-66) and human embryonic kidney 293T (HEK293T) cells were used for in vitro analysis. Transfection experiments were performed with synthetic miRNA mimics for miR-369-3p and small interfering RNAs for TSPAN13. Relative expression of miR-369-3p and TSPAN13 mRNA was determined by RT-qPCR. Protein levels of TSPAN13 were determined by western blotting. Cell proliferation (CCK-8 assay), colony formation, and apoptosis (flow cytometry) were analyzed in transfected cells. Binding sites of miR-369-3p in TSPAN13 mRNA were determined by bioinformatics analysis and dual luciferase reporter assay. miR-369-3p was downregulated and TSPAN13 upregulated in PTC, follicular thyroid cancer, and tall cell variant tissues. Both low expression of miR-369-3p and high expression of TSPAN13 were associated with shorter OS in thyroid cancer patients. Overexpression of miR-369-3p significantly suppressed proliferation and promoted apoptosis in PTC cells. TSPAN13 was a direct target of miR-369-3p, and silencing of TSPAN13 phenocopied the effect of miR-369-3p mimics in PTC cells. Overall, the downregulation of miR-369-3p and consequent upregulation of its target TSPAN13 appear to be involved in pathophysiology of PTC.

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