scholarly journals Identification of key genes of papillary thyroid carcinoma by integrated bioinformatics analysis

2020 ◽  
Author(s):  
Gang Xue ◽  
Xu Lin ◽  
Jingfang Wu ◽  
Da Pei ◽  
Dong-Mei Wang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Disease Free Survival ◽  
Tnm Staging ◽  
Mrna Levels ◽  
Papillary Thyroid ◽  
Rna Seq ◽  
Positive Role ◽  
Immune Infiltration ◽  
Key Genes

Abstract Background:Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers. Methods:In this study, 4 pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes (DEGs) were screened. The results of GO and KEGG enrichment analysis indicate that the vast majority of DEGs may play a positive role in the development of cancer. Then, the significant modules were analysed using Cytoscape software in the protein-protein interaction (PPI) network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes are all analyzed. And the expression of ADORA1, APOE and LPAR5 genes was verified by qPCR in papillary thyroid carcinoma compared to their matching adjacent tissues.Results: A total of 25 genes were identified as hub genes with nodes greater than 10. The expression of 25 key genes in PTC were verified by the GEPIA database, and the overall survival and disease free survival analyses of these key genes were conducted with Kaplan–Meier plots. We found that only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes are significantly correlated with the TNM staging of PTC, and these three genes are related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR further confirmed the reliability of our results. Conclusion: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.Key words :RNA-Seq, papillary thyroid carcinoma, key gene, bioinformatics

scholarly journals Identification of key genes of papillary thyroid carcinoma by integrated bioinformatics analysis

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Gang Xue ◽  
Xu Lin ◽  
Jing-Fang Wu ◽  
Da Pei ◽  
Dong-Mei Wang ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differentially Expressed Genes ◽  
Disease Free Survival ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Papillary Thyroid ◽  
Positive Role ◽  
Immune Infiltration ◽  
Key Genes

Abstract Background: Papillary thyroid carcinoma (PTC) is one of the fastest-growing malignant tumor types of thyroid cancer. Therefore, identifying the interaction of genes in PTC is crucial for elucidating its pathogenesis and finding more specific molecular biomarkers. Methods: Four pairs of PTC tissues and adjacent tissues were sequenced using RNA-Seq, and 3745 differentially expressed genes were screened (P<0.05, |logFC|>1). The enrichment analysis indicated that the vast majority of differentially expressed genes (DEGs) may play a positive role in the development of cancer. Then, the significant modules were analyzed using Cytoscape software in the protein–protein interaction network. Survival analysis, TNM analysis, and immune infiltration analysis of key genes were analyzed. And the expression of ADORA1, APOE, and LPAR5 genes were verified by qPCR in PTC compared with matching adjacent tissues. Results: Twenty-five genes were identified as hub genes with nodes greater than 10. The expression of 25 genes were verified by the GEPIA database, and the overall survival and disease-free survival analyses were conducted with Kaplan–Meier plotter. We found only three genes were confirmed with our validation and were statistically significant in PTC, namely ADORA1, APOE, and LPAR5. Further analysis found that the mRNA levels and methylation degree of these three genes were significantly correlated with the TNM staging of PTC. And these three genes were related to PTC immune infiltration. Verification of the expression of these three genes by RT-qPCR and Western blot further confirmed the reliability of our results. Conclusion: Our study identified three genes that may play key regulatory roles in the development, metastasis, and immune infiltration of papillary thyroid carcinoma.

scholarly journals A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma

2017 ◽  
Vol 6 (3) ◽  
pp. R8-R17 ◽  
Author(s):  
Huy Gia Vuong ◽  
Uyen N P Duong ◽  
Ahmed M A Altibi ◽  
Hanh T T Ngo ◽  
Thong Quang Pham ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Random Effect ◽  
Random Effect Model ◽  
Disease Free Survival ◽  
Papillary Thyroid ◽  
Promoter Mutation ◽  
Meta Analyses ◽  
The Impact

The prognostic role of molecular markers in papillary thyroid carcinoma (PTC) is a matter of ongoing debate. The aim of our study is to investigate the impact of RAS, BRAF, TERT promoter mutations and RET/PTC rearrangements on the prognosis of PTC patients. We performed a search in four electronic databases: PubMed, Scopus, Web of Science and Virtual Health Library (VHL). Data of hazard ratio (HR) and its 95% confidence interval (CI) for disease-specific survival (DSS) and disease-free survival (DFS) were directly obtained from original papers or indirectly estimated from Kaplan–Meier curve (KMC). Pooled HRs were calculated using random-effect model weighted by inverse variance method. Publication bias was assessed by using Egger’s regression test and visual inspection of funnel plots. From 2630 studies, we finally included 35 studies with 17,732 patients for meta-analyses. TERT promoter mutation was significantly associated with unfavorable DSS (HR = 7.64; 95% CI = 4.00–14.61) and DFS (HR = 2.98; 95% CI = 2.27–3.92). BRAF mutations significantly increased the risk for recurrence (HR = 1.63; 95% CI = 1.27–2.10) but not for cancer mortality (HR = 1.41; 95% CI = 0.90–2.23). In subgroup analyses, BRAF mutation only showed its prognostic value in short-/medium-term follow-up. Data regarding RAS mutations and RET/PTC fusions were insufficient for meta-analyses. TERT promoter mutation can be used as an independent and reliable marker for risk stratification and predicting patient’s outcomes. The use of BRAF mutation to assess patient prognosis should be carefully considered.

scholarly journals MAPK and SHH pathways modulate type 3 deiodinase expression in papillary thyroid carcinoma

2016 ◽  
Vol 23 (3) ◽  
pp. 135-146 ◽  
Author(s):  
Mírian Romitti ◽  
Simone Magagnin Wajner ◽  
Lucieli Ceolin ◽  
Carla Vaz Ferreira ◽  
Rafaela Vanin Pinto Ribeiro ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Phase Cell ◽  
Mrna Levels ◽  
Papillary Thyroid ◽  
Shh Pathway ◽  
Cycle Arrest ◽  
Type 3 ◽  
Sustained Activation

Type 3 deiodinase (DIO3, D3) is reactivated in human neoplasias. Increased D3 levels in papillary thyroid carcinoma (PTC) have been associated with tumor size and metastatic disease. The objective of this study is to investigate the signaling pathways involved inDIO3upregulation in PTC. Experiments were performed in human PTC cell lines (K1 and TPC-1 cells) or tumor samples.DIO3mRNA and activity were evaluated by real-time PCR and ion-exchange column chromatography respectively. Western blot analysis was used to determine the levels of D3 protein.DIO3gene silencing was performed via siRNA transfection.DIO3mRNA levels and activity were readily detected in K1 (BRAFV600E) and, at lower levels, in TPC-1 (RET/PTC1) cells (P<0.007 andP=0.02 respectively). Similarly,DIO3mRNA levels were higher in PTC samples harboring theBRAFV600Emutation as compared with those with RET/PTC1 rearrangement or negative for these mutations (P<0.001). Specific inhibition ofBRAFoncogene (PLX4032, 3 μM), MEK (U0126, 10–20 μM) or p38 (SB203580, 10–20 μM) signaling was associated with decreases inDIO3expression in K1 and TPC-1 cells. Additionally, the blockage of the sonic hedgehog (SHH) pathway by cyclopamine (10 μM) resulted in markedly decreases inDIO3mRNA levels. Interestingly, siRNA-mediatedDIO3silencing induced decreases on cyclin D1 expression and partial G1 phase cell cycle arrest, thereby downregulating cell proliferation. In conclusion, sustained activation of the MAPK and SHH pathways modulate the levels ofDIO3expression in PTC. Importantly,DIO3silencing was associated with decreases in cell proliferation, thus suggesting a D3 role in tumor growth and aggressiveness.

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 BRAF V600E mutation in papillary thyroid carcinoma: it’s relation to clinical features and oncologic outcomes in a single cancer centre experience

2021 ◽  
Author(s):  
Mahmoud Al-Masri ◽  
Tawfiq Al-Shobaki ◽  
Hani Al-Najjar ◽  
Rafal Iskanderian ◽  
Enas Younis ◽  
...  
Keyword(s):  
Overall Survival ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Disease Free Survival ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Cancer Center ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Disease Free

Purpose: This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern PTC patients treated at a single centre. We test the association of BRAFV600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. Methods: Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short and long termed were collected. Results: A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumor size for patients with a negative BRAF V600E mutation were significantly larger in comparison to patients who tested positive for the mutation (3.47 cm versus 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0-168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3-142)) (P= 0.162, HR=0.731) Furthermore, both groups showed similar overall survival rates: positive = 94.5% (median 56 months (0-228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3-157)) (P = 0.941, HR= 0.940). Conclusion: BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival or disease-free survival. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high risk groups.

scholarly journals Clinical outcomes of low-dose and high-dose postoperative radioiodine therapy in intermediate-risk papillary thyroid carcinoma patients with low postoperative stimulated thyroglobulin (1-20 ng/ml) and non-structural or functional metastasis: study protocol for a randomized-controlled trial

2021 ◽  
Author(s):  
Pan Chen ◽  
Jia-Xin Luo ◽  
Wei Ouyang ◽  
Hui-Juan Feng ◽  
Ju-Qing Wu ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Dose Group ◽  
Low Dose ◽  
Disease Free Survival ◽  
High Dose Group ◽  
High Dose ◽  
Intermediate Risk ◽  
Papillary Thyroid ◽  
Free Survival

Abstract Background: For some intermediate risk papillary thyroid carcinoma patients, if there are structural metastases, reoperation is preferred. If there are functional metastases (131I avidity), they can be treated with high-dose radioactive iodine (131I). However, it is still controversial whether 131I ablation should be used and the determination of 131I dosage for another part of intermediate risk patients with non-structural or functional metastases, especially those with postoperative stimulated thyroglobulin (ps-Tg) 1-20 ng/ml. The aim of the present study is mainly to compare the 3-years disease-free survival between low-dose group (1.1 GBq) and high-dose group (3.7 GBq) in intermediate risk papillary thyroid carcinoma patients with non-structural or functional metastases and ps-Tg 1-20 ng/ml.Methods: A single-center, randomized, double-blind parallel controlled study is designed at the Zhujiang Hospital of Southern Medical University. Participants will be randomized to low-dose group (1.1 GBq) or high-dose group (3.7 GBq) in a 1:1 ratio. After orally receiving different dosage of 131I once on an empty stomach, all patients will return to our hospital every 3-12 months to be performed related inspection items. Discussion: We believe that the 3-year disease-free survival of low-dose group (1.1 GBq) may not be lower than that of high-dose group (3.7 GBq) in intermediate-risk thyroid papillary carcinoma patients with no structural or functional metastases and ps-Tg 1-20 ng/ml. Besides we expect to clarify whether there are apparent differences in successful remnant ablation, efficacy, progression-free survival, safety, and health economics evaluation between the two groups.Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov/), ID: NCT04354324. Registered on 16 April, 2020.

scholarly journals TERT Genetic Polymorphism rs2736100 Was Associated With Papillary Thyroid Carcinoma Aggressive Manifestation

2021 ◽  
Author(s):  
Xilin Nie ◽  
Jinbiao Shang ◽  
Wendong Wang
Keyword(s):  
Genetic Polymorphism ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cox Regression ◽  
Cell Transformation ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Papillary Thyroid ◽  
Lateral Lymph Node ◽  
Tumor Spread

Abstract Background: The TERT rs2736100 genetic polymorphism was commonly found in human malignancies, indicated its key role in cancer cell transformation. The aim of this study was to investigate the effects of the functional TERT rs2736100 genetic polymorphism in papillary thyroid carcinoma (PTC) patients` outcomes.Methods: We had performed a retrospective study of the relationship betweenrs2736100and clinicopathological outcomes of PTC in 500 patients (378 female and 122 male) aged 43.8±11.4 years (rang 15-74 years) with median follow-up of 60 months (range, 1 to 455 months). Results: The TERT rs2736100 genetic polymorphism (TG/GG versus TT) were significantly associated with several high risk clinicopathological features such as tumor spread, extra-thyroidal extension, central/lateral lymph node metastases, stage T III or IV disease. However, in the Kaplan-Meier survival analyses, the rs2736100 mutation was unrelated to the overall disease-free survival with a log-rank p>0.05. In the Cox-regression analyses, the overall survival rate of recurrence/neo-metastasis was related with lager size of tumor, younger age and tumor spread, but unrelated with rs2736100 mutation. Conclusion: The TERT rs2736100 genetic polymorphism positive was more likely to manifest with aggressive clinicopathological characteristics but cannot worse prognosis much in PTC.

scholarly journals Impact of Multifocality on the Recurrence of Papillary Thyroid Carcinoma

2021 ◽  
Vol 10 (21) ◽  
pp. 5144
Author(s):  
Joohyun Woo ◽  
Hyeonkyeong Kim ◽  
Hyungju Kwon
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cox Regression ◽  
Medical Center ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Cox Regression Analysis

The incidence of thyroid cancer has dramatically increased over the last few decades, and up to 60% of patients have multifocal tumors. However, the prognostic impact of multifocality in patients with papillary thyroid carcinoma (PTC) remains unestablished and controversial. We evaluate whether multifocality can predict the recurrence of PTC. A total of 1249 patients who underwent total thyroidectomy for PTC at the Ewha Medical Center between March 2012 and December 2019 were reviewed. In this study, multifocality was found in 487 patients (39.0%) and the mean follow-up period was 5.5 ± 2.7 years. Multifocality was associated with high-risk features for recurrence, including extrathyroidal extension, lymph node metastasis, and margin involvement. After adjustment of those clinicopathological features, 10-year disease-free survival was 93.3% in patients with multifocal tumors, whereas those with unifocal disease showed 97.6% (p = 0.011). Multivariate Cox regression analysis indicated that male sex (HR 2.185, 95% CI 1.047–4.559), tumor size (HR 1.806, 95% CI 1.337–2.441), N1b LN metastasis (HR 3.603, 95% CI 1.207–10.757), and multifocality (HR 1.986, 95% CI 1.015–3.888) were independent predictors of recurrence. In conclusion, multifocality increased the risk of recurrence in patients with PTC. Patients with multifocal PTCs may need judicious treatment and follow-up approaches.

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