scholarly journals Identification of Lipid Metabolism-Related Genes as Prognostic Indicators in Papillary Thyroid Cancer

2021 ◽  
Author(s):  
Shi-Shuai Wen ◽  
Yi Luo ◽  
Wei-Li Wu ◽  
Ting Zhang ◽  
Yi-Chen Yang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lipid Metabolism ◽  
Papillary Thyroid Cancer ◽  
Expression Profiles ◽  
Locally Advanced ◽  
Gene Signature ◽  
Structural Basis ◽  
Clinicopathological Parameters ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Abstract Purpose Lipid metabolism plays important roles not only in the structural basis and energy supply of healthy cells but also in the oncogenesis and progression of cancer. In this study, we investigate the prognostic value of lipid metabolism related genes in papillary thyroid cancer (PTC). Methods The in time to recurrence predictive gene signature was developed, internally and externally validated based on PTC datasets including The Cancer Genome Atlas (TCGA) and GSE33630 datasets. Univariate, LASSO and multivariate Cox regression analysis were applied to assess prognostic genes and build the prognostic gene signature. The expression profiles of prognostic genes were further determined by immunohistochemistry by using in-house cohorts which enrolled 97 patients. Kaplan-Meier curve, time-dependent receiver operating characteristic curve, nomogram and decision curve analysis were used to assess the performance of the gene signature. Results We identified four recurrence-related genes, PDZK1IP1, TMC3, LRP2 and KCNJ13, and established a 4-gene signature recurrence risk model. The expression profile of the 4 genes in the TCGA and in-house cohort indicated that stage T1/T2 PTC and locally advanced PTC exhibited notable associations not only with clinicopathological parameters but also with recurrence. Calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. GSEA showed that high-risk cases exhibited changes in several important tumorigenesis-related pathways, such as the intestinal immune network and the p53 and Hedgehog signalling pathways. Conclusion Our findings indicate that lipid metabolism-related gene profiling represents a potential marker for prognosis and treatment decisions for PTC patients.

scholarly journals Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer

2018 ◽  
Vol 19 (10) ◽  
pp. 2867 ◽  
Author(s):  
Woo Lee ◽  
Seul Lee ◽  
Seung Yim ◽  
Daham Kim ◽  
Hyunji Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Exome Sequencing ◽  
Papillary Thyroid Cancer ◽  
Whole Exome Sequencing ◽  
Primary Tumor ◽  
Tumor Heterogeneity ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Whole Exome ◽  
Advanced Thyroid Cancer

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide ‘A’ at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

Characteristics of lipid metabolism-related gene expression-based molecular subtype in papillary thyroid cancer

2020 ◽  
Vol 52 (10) ◽  
pp. 1166-1170
Author(s):  
Midie Xu ◽  
Tuanqi Sun ◽  
Shishuai Wen ◽  
Tingting Zhang ◽  
Xin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Lipid Metabolism ◽  
Papillary Thyroid Cancer ◽  
Molecular Subtype ◽  
Papillary Thyroid ◽  
Related Gene

scholarly journals Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3624
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Zeeshan Qadri ◽  
Khawar Siddiqui ◽  
Saif S. Al-Sobhi ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Hazard Rate ◽  
Tumor Recurrence ◽  
Cox Regression ◽  
Middle Eastern ◽  
Treatment Strategies ◽  
Recurrence Risk ◽  
Papillary Thyroid ◽  
Cox Regression Analysis

Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

scholarly journals The molecular and gene/miRNA expression profiles of radioiodine resistant papillary thyroid cancer

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Carla Colombo ◽  
Emanuela Minna ◽  
Chiara Gargiuli ◽  
Marina Muzza ◽  
Matteo Dugo ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Tissue Type ◽  
Molecular Profile ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Disease Persistence

Abstract Background Papillary thyroid cancer (PTC) is the most frequent endocrine tumor. Radioiodine (RAI) treatment is highly effective in these tumors, but up to 60% of metastatic cases become RAI-refractory. Scanty data are available on either the molecular pattern of radioiodine refractory papillary thyroid cancers (PTC) or the mechanisms responsible for RAI resistance. Methods We analyzed the molecular profile and gene/miRNA expression in primary PTCs, synchronous and RAI-refractory lymph node metastases (LNMs) in correlation to RAI avidity or refractoriness. We classified patients as RAI+/D+ (RAI uptake/disease persistence), RAI−/D+ (absent RAI uptake/disease persistence), and RAI+/D- (RAI uptake/disease remission), and analyzed the molecular and gene/miRNA profiles, and the expression of thyroid differentiation (TD) related genes. Results A different molecular profile according to the RAI class was observed: BRAFV600E cases were more frequent in RAI−/D+ (P = 0.032), and fusion genes in RAI+/D+ cases. RAI+/D- patients were less frequently pTERT mutations positive, and more frequently wild type for the tested mutations/fusions. Expression profiles clearly distinguished PTC from normal thyroid. On the other hand, in refractory cases (RAI+/D+ and RAI−/D+) no distinctive PTC expression patterns were associated with either tissue type, or RAI uptake, but with the driving lesion and BRAF−/RAS-like subtype. Primary tumors and RAI-refractory LNMs with BRAFV600E mutation display transcriptome similarity suggesting that RAI minimally affects the expression profiles of RAI-refractory metastases. Molecular profiles associated with the expression of TPO, SLC26A4 and TD genes, that were found more downregulated in BRAFV600E than in gene fusions tumors. Conclusions The present data indicate a different molecular profile in RAI-avid and RAI-refractory metastatic PTCs. Moreover, BRAFV600E tumors displayed reduced differentiation and intrinsic RAI refractoriness, while PTCs with fusion oncogenes are RAI-avid but persistent, suggesting different oncogene-driven mechanisms leading to RAI refractoriness.

scholarly journals The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice. 

2020 ◽  
Author(s):  
Krzysztof Kaliszewski ◽  
Dorota Diakowska ◽  
Łukasz Nowak ◽  
Beata Wojtczak ◽  
Jerzy Rudnicki
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Locally Advanced Disease ◽  
In Series ◽  
8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

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.

scholarly journals The Age Threshold of the 8th Edition AJCC Classification Is Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice. 

2020 ◽  
Author(s):  
Krzysztof Kaliszewski ◽  
Dorota Diakowska ◽  
Łukasz Nowak ◽  
Beata Wojtczak ◽  
Jerzy Rudnicki
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Locally Advanced Disease ◽  
In Series ◽  
8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cut off 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

scholarly journals The Age Threshold of the 8th Edition AJCC ClassificationIs Useful for Indicating Patients with Aggressive Papillary Thyroid Cancer in Clinical Practice.

2020 ◽  
Author(s):  
Krzysztof Kaliszewski ◽  
Dorota Diakowska ◽  
Łukasz Nowak ◽  
Beata Wojtczak ◽  
Jerzy Rudnicki
Keyword(s):  
Thyroid Cancer ◽  
Clinical Practice ◽  
Risk Stratification ◽  
Papillary Thyroid Cancer ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Papillary Thyroid ◽  
Locally Advanced Disease ◽  
In Series ◽  
8Th Edition

Abstract Background: Papillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classificationis to increase the age cutoff for risk stratification in PTC from 45 to 55 years. However, whether this cutoff is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.Methods: We retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n=523) were divided in 2 groups according to age cutoff. In the first series (cutoff 45) patients <45 (n=193) vs. ≥45 (n=330) were compared, and in the second series (cutoff 55) patients <55 (n=306) vs. ≥55 (n=217) were compared.Results: The rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p=0.013). No significant differences were found for this parameter in series with cutoff point 45 years old. A significantly higher risk of locally advanced disease T3+T4 (OR=4.87) and presence of LNM (N1) (OR=3.78) was observed in ≥45 years old group (p=0.021 and p<0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3+T4) was higher (OR=5.21) and LNM presence was OR=4.76 (p<0.001 and p<0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p<0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.Conclusions: The age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

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