Development and validation of a ferroptosis-related prognostic model for the prediction of progression-free survival and immune microenvironment in patients with papillary thyroid carcinoma

2021 ◽  
Vol 101 ◽  
pp. 108156
Author(s):  
Yinde Huang ◽  
Zhenyu Xie ◽  
Xin Li ◽  
Wenbin Chen ◽  
Yuzhen He ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Prognostic Model ◽  
Progression Free Survival ◽  
Papillary Thyroid ◽  
Immune Microenvironment ◽  
Free Survival ◽  
Development And Validation

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 FK506-binding protein 5 promotes the progression of papillary thyroid carcinoma

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110083
Author(s):  
Zhenya Gao ◽  
Fang Yu ◽  
Huanxia Jia ◽  
Zhuo Ye ◽  
Shijie Yao
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Binding Protein ◽  
Progression Free Survival ◽  
Papillary Thyroid ◽  
Expression Levels ◽  
Fk506 Binding Protein ◽  
Normal Tissues ◽  
Induced Apoptosis

Objective To detect the expression of FK506-binding protein 5 (FKBP5) in human papillary thyroid carcinoma (PTC) tissues, and explore its possible role in the progression of PTC. Methods FKBP5 expression levels were assessed in 115 PTC tissues and corresponding normal tissues by immunohistochemistry. We also examined the correlations between FKBP5 expression and clinicopathological factors and survival in 75 patients with PTC. The effects of FKBP5 on the proliferation and apoptosis of PTC cells were detected by colony-formation, MTT, and flow cytometry assays, respectively. We further investigated the effects of FKBP5 on tumor growth in mice. Results We revealed high expression levels of FKBP5 in human PTC tissues compared with normal tissues. Furthermore, high FKBP5 expression was associated with an increased incidence of intraglandular dissemination, and lower overall and progression-free survival. FKBP5 depletion remarkably suppressed the proliferation and induced apoptosis of PTC cells in vitro. FKBP5 further contributed to the growth of PTC tumors in mice. Conclusions The results of this study demonstrated the potential involvement of FKBP5 in the progression of PTC, and confirmed FKBP5 as a novel therapeutic target for PTC treatment.

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.

scholarly journals Efficacy and safety of lenvatinib in an elderly patient with metastatic papillary thyroid carcinoma and cardiological comorbidity: a case report

2019 ◽  
Vol 15 (24s) ◽  
pp. 27-33 ◽  
Author(s):  
Agnese Latorre ◽  
Agnese Maria Fioretti ◽  
Francesco Giotta ◽  
Vito Lorusso
Keyword(s):  
Atrial Fibrillation ◽  
Thyroid Carcinoma ◽  
Progression Free Survival ◽  
Chronic Atrial Fibrillation ◽  
Differentiated Thyroid Carcinoma ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Select Trial

Lenvatinib significantly prolonged progression-free survival versus placebo in patients with radio-iodine refractory differentiated thyroid carcinoma. However, the primary adverse effects of any grade that occurred in >40% of patients in the lenvatinib group of the Phase III SELECT trial was hypertension (67.8%). Therefore, this drug should be used with caution in patients with cardiological morbidity. Here, we describe the case of a 73-year-old man with hypertension, obesity and chronic atrial fibrillation, who received lenvatinib for 6 months in the absence of cardiological symptoms.

scholarly journals Is Completion Thyroidectomy Necessary in Patients with Papillary Thyroid Carcinoma who Underwent Lobectomy?

2021 ◽  
Vol 37 (2) ◽  
pp. 25-31
Author(s):  
Il Ku Kang ◽  
Kwangsoon Kim ◽  
Ja Seong Bae ◽  
Jeong Soo Kim
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Lymph Nodes ◽  
Disease Free Survival ◽  
Completion Thyroidectomy ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Disease Free ◽  
Positive Lymph Nodes

Background/Objectives: Although thyroid lobectomy recently is considered as sufficient for low-risk papillary thyroid carcinoma (PTC), completion thyroidectomy is required due to the insufficiency of the preoperative evaluation. The aim of this study was to investigate recurrence rate and disease free survival depending on the gross extrathyroidal extension (gETE) or the number of metastatic lymph node identified in patients with PTC.Materials & Methods: We assessed 3373 patients with PTC who underwent lobectomy at Seoul St. Mary’s Hospital (Seoul, Korea) between January 2009 and December 2014. Clinicopathological characteristics and long-term surgical outcomes were retrospectively analyzed through complete chart reviews. The mean follow-up duration was 97.1 ± 21.4 months.Results: The rate of recurrence was higher in gETE group (1.8% vs. 6.0%, p=0.004), leading to decreased disease free survival in Kaplan-Meier analysis (log-rank p<0.001). N1 group (n=1389) was analyzed into two groups whether the number of positive nodes is more than 5 or less. For the group of the more metastatic nodes, the recurrence rate higher compared to the other group (3.0% vs. 9.3%, p<0.001). DFS was longer in the group that had lesser metastatic nodes (log-rank p<0.001). However, in terms of N1 group over 1cm (n=492), No statistical difference was observed according to the number of positive lymph nodes (4.5% vs. 9.1%, p=0.092)Conclusion: When it comes to node positive PTC, Despite the number of positive lymph nodes was over 5, follow-up with no further surgery can be an option.

scholarly journals Analysis of the prognostic significance and potential mechanisms of lncRNAs associated with m6A methylation in papillary thyroid carcinoma

2021 ◽  
Author(s):  
Yinde Huang ◽  
Xin Li ◽  
Wenbin Chen ◽  
Yuzhen He ◽  
Song Wu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Tumor Microenvironment ◽  
Thyroid Carcinoma ◽  
Immune Checkpoint ◽  
Prognostic Model ◽  
Prognostic Markers ◽  
Clinicopathological Characteristics ◽  
Papillary Thyroid ◽  
The Relationship ◽  
Pan Cancer

Abstract Background : m6A methylation-related long non-coding RNAs (lncRNAs) play a significant role in the progression of various tumors and can be used as prognostic markers. However, whether m6A-related lncRNAs also play the same function as prognostic markers in papillary thyroid carcinoma (PTC) remains unclear. Methods : Consensus cluster analysis was performed to divide PTC samples obtained from The Cancer Genome Atlas database into two clusters according to the expression of m6A-related lncRNAs. Then, the least absolute shrinkage and selection operator (LASSO) regression analysis was performed to create and verify a prognostic model. Furthermore, the relationship among risk scores, clusters, programmed death-ligand 1 (PD-L1), tumor microenvironment (TME), clinicopathological characteristics, immune infiltration, immune checkpoint, and tumor mutation burden (TMB) was analyzed. In addition, a nomogram was created, and subsequently, the drug sensitivity of lncRNAs in the prognostic model was analyzed. Finally, the relationship between these lncRNAs and prognosis in pan-cancer was investigated. Results: The prognosis, RAS, BRAF, M, and TME were found to be different in two clusters. The prognostic model included three lncRNAs: PSMG3-AS1 , BHLHE40-AS1 , and AC016747.3 . The risk score was associated with clusters, PD-L1, tumor microenvironment, clinicopathological characteristics, immune cell infiltration, immune checkpoint, and TMB, and thus, risk score was confirmed as useful prognostic indicators. Differentially expressed lncRNAs are involved in many malignancies and can be identified as cancer prognostic makers. Conclusion : According to our research, we can regard m6A-related lncRNAs involved in the procession of PTC as a biomarker of PFS for PTC patients, and pan-cancer.

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