scholarly journals Molecular classification of follicular thyroid carcinoma based on TERT promoter mutations

2021 ◽  
Author(s):  
Hyunju Park ◽  
Hyeong Chan Shin ◽  
Heera Yang ◽  
Jung Heo ◽  
Chang-Seok Ki ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Cox Regression ◽  
Follicular Thyroid Carcinoma ◽  
Disease Free Survival ◽  
Molecular Classification ◽  
Clinicopathological Characteristics ◽  
World Health ◽  
Cancer Specific Survival ◽  
Health Organization ◽  
Promoter Mutations

AbstractFollicular thyroid carcinoma (FTC) has different clinicopathological characteristics than papillary thyroid carcinoma. However, there are no independent systems to predict cancer-specific survival (CSS) in FTC. Telomerase reverse transcriptase (TERT) promoter mutations are associated with tumor aggressiveness. Thus, it could be a potential prognostic marker. The aim of this study was to refine the CSS risk prediction using TERT promoter mutations in combination with the fourth edition of World Health Organization (WHO 2017) morphological classification. We investigated 77 FTC patients between August 1995 and November 2020. Cox regression was used to calculate hazard ratios to derive alternative groups. Disease-free survival (DFS) and CSS predictability were compared using Proportion of variation explained (PVE) and C-index. CSS was significantly different in encapsulated angioinvasive (EA)-FTC patients stratified by TERT promoter mutations [wild-type (WT-TERT) vs. mutant (M-TERT); P < 0.001] but not in minimally invasive (MI)-FTC and widely invasive (WI)-FTC patients (P = 0.691 and 0.176, respectively). We defined alternative groups as follows: Group 1 (MI-FTC with WT-TERT and M-TERT; EA-FTC with WT-TERT), Group 2 (WI-FTC with WT-TERT), and Group 3 (EA-FTC with M-TERT; WI-FTC with M-TERT). Both PVE (22.44 vs. 9.63, respectively) and C-index (0.831 vs. 0.731, respectively) for CSS were higher in the alternative groups than in the WHO 2017 groups. Likewise, both PVE (27.1 vs. 14.9, respectively) and C-index (0.846 vs. 0.794, respectively) for DFS were also higher in the alternative groups than in the WHO 2017 groups. Alternative group harmonizing of the WHO 2017 classification and TERT promoter mutations is effective in predicting CSS in FTC patients, thereby improving DFS predictability.

scholarly journals Comprehensive Genetic Analysis of Follicular Thyroid Carcinoma Predicts Prognosis Independent of Histology

2018 ◽  
Vol 103 (7) ◽  
pp. 2640-2650 ◽  
Author(s):  
Norman G Nicolson ◽  
Timothy D Murtha ◽  
Weilai Dong ◽  
Johan O Paulsson ◽  
Jungmin Choi ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Somatic Mutations ◽  
Follicular Thyroid Carcinoma ◽  
World Health ◽  
Histopathological Classification ◽  
Mutation Burden ◽  
Clonality Analysis ◽  
Widely Invasive ◽  
Health Organization ◽  
Genetic Signatures

Abstract Context Follicular thyroid carcinoma (FTC) is classified into minimally invasive (miFTC), encapsulated angioinvasive (eaFTC), and widely invasive (wiFTC) subtypes, according to the 2017 World Health Organization guidelines. The genetic signatures of these subtypes may be crucial for diagnosis, prognosis, and treatment but have not been described. Objective Identify and describe the genetic underpinnings of subtypes of FTC. Methods Thirty-nine tumors, comprising 12 miFTCs, 17 eaFTCs, and 10 wiFTCs, were whole-exome sequenced and analyzed. Somatic mutations, constitutional sequence variants, somatic copy number alterations, and mutational signatures were described. Clinicopathologic parameters and mutational profiles were assessed for associations with patient outcomes. Results Total mutation burden was consistent across FTC subtypes, with a median of 10 (range 1 to 44) nonsynonymous somatic mutations per tumor. Overall, 20.5% of specimens had a mutation in the RAS subfamily (HRAS, KRAS, or NRAS), with no notable difference between subtypes. Mutations in TSHR, DICER1, EIF1AX, KDM5C, NF1, PTEN, and TP53 were also noted to be recurrent across the cohort. Clonality analysis demonstrated more subclones in wiFTC. Survival analysis demonstrated worse disease-specific survival in the eaFTC and wiFTC cohorts, with no recurrences or deaths for patients with miFTC. Mutation burden was associated with worse prognosis, independent of histopathological classification. Conclusions Though the number and variety of somatic variants are similar in the different histopathological subtypes of FTC in our study, mutational burden was an independent predictor of mortality and recurrence.

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.

Development and Validation of Prognostic Nomograms Predicting Recurrence and Survival in Patients with Solitary Hepatocellular Carcinoma Following Curative Liver Resection

2021 ◽  
Author(s):  
Xinxin Chen ◽  
Wenxia Qiu ◽  
Xuekun Xie ◽  
Zefeng Chen ◽  
Zhiwei Han ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Tumor Diameter ◽  
Cox Regression Analysis ◽  
Tumor Capsule ◽  
Calibration Curves ◽  
Solitary Hepatocellular Carcinoma

Abstract Background: This work was designed to establish and verify our nomograms integrating clinicopathological characteristics with hematological biomarkers to predict both disease-free survival (DFS) and overall survival (OS) in solitary hepatocellular carcinoma (HCC) patients following hepatectomy.Methods: We scrutinized the data retrospectively from 414 patients with a clinicopathological diagnosis of solitary HCC from Guangxi Medical University Cancer Hospital (Nanning, China) between January 2004 and December 2012. Following the random separation of the samples in a 7:3 ratio into the training set and validation set, the former set was assessed by Cox regression analysis to develop two nomograms to predict the 1-year and 3-year DFS and OS (3-years and 5-years). This was followed by discrimination and calibration estimation employing Harrell’s C-index (C-index) and calibration curves, while the internal validation was also assessed.Results: In the training cohort, the tumor diameter, tumor capsule, macrovascular invasion, and alpha-fetoprotein (AFP) were included in the DFS nomogram. Age, tumor diameter, tumor capsule, macrovascular invasion, microvascular invasion, and aspartate aminotransferase (AST) were included in the OS nomogram. The C-index was 0.691 (95% CI: 0.644-0.738) for the DFS-nomogram and 0.713 (95% CI: 0.670-0.756) for the OS-nomogram. The survival probability calibration curves displayed a fine agreement between the predicted and observed ranges in both data sets. Conclusion: Our nomograms combined clinicopathological features with hematological biomarkers to emerge effective in predicting the DFS and OS in solitary HCC patients following curative liver resection. Therefore, the potential utility of our nomograms for guiding individualized treatment clinically and monitor the recurrence monitoring in these patients.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

scholarly journals Disability in people clinically at high risk of psychosis

2010 ◽  
Vol 197 (4) ◽  
pp. 278-284 ◽  
Author(s):  
Eva Velthorst ◽  
Dorien H. Nieman ◽  
Don Linszen ◽  
Hiske Becker ◽  
Lieuwe de Haan ◽  
...  
Keyword(s):  
High Risk ◽  
Help Seeking ◽  
Cox Regression ◽  
World Health ◽  
Disability Assessment ◽  
Community Activities ◽  
Transition Group ◽  
The World ◽  
Health Organization

BackgroundDecline in social functioning occurs in individuals who later develop psychosis.AimsTo investigate whether baseline differences in disability are present in those who do and those who do not make a transition to psychosis in a group clinically at high risk and whether disability is a risk factor for transition.MethodProspective multicentre, naturalistic field study with an 18-month follow-up period on 245 help-seeking individuals clinically at high risk. Disability was assessed with the Disability Assessment Schedule of the World Health Organization (WHODAS–II).ResultsAt baseline, the transition group displayed significantly greater difficulties in making new friends (z =−3.40, P = 0.001), maintaining a friendship (z =−3.00, P = 0.003), dealing with people they do not know (z =−2.28, P = 0.023) and joining community activities (z =−2.0, P = 0.05) compared with the non-transition group. In Cox regression, difficulties in getting along with people significantly contributed to the prediction of transition to psychosis in our sample (β = 0.569, s.e. = 0.184, Wald = 9.548, P = 0.002, hazard ratio (HR) = 1.767, 95% CI 1.238–2.550).ConclusionsCertain domains of social disability might contribute to the prediction of psychosis in a sample clinically at high risk.

scholarly journals TERT Immunohistochemistry Is a Poor Predictor of TERT Promoter Mutations and Gene Expression in Follicular Thyroid Carcinoma

2018 ◽  
Vol 29 (4) ◽  
pp. 380-383 ◽  
Author(s):  
Johan O. Paulsson ◽  
Anton Olander ◽  
Felix Haglund ◽  
Jan Zedenius ◽  
C. Christofer Juhlin
Keyword(s):  
Gene Expression ◽  
Thyroid Carcinoma ◽  
Follicular Thyroid Carcinoma ◽  
Poor Predictor ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8602 ◽  
Author(s):  
Xiangyan Zhang ◽  
Jie Wu ◽  
Lili Wang ◽  
Han Zhao ◽  
Hong Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Eastern China ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Molecular Classification ◽  
Clinicopathological Characteristics ◽  
Stage I ◽  
Chinese Patients ◽  
Poor Differentiation ◽  
Colorectal Cancer Patients

Objective To investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC). Methods Clinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined. Results The amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014). Conclusion The prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

scholarly journals Triglyceride glucose-body mass index in identifying high-risk groups of pre-diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Chunyuan Jiang ◽  
Ruijuan Yang ◽  
Maobin Kuang ◽  
Meng Yu ◽  
Mingchun Zhong ◽  
...  
Keyword(s):  
Body Mass Index ◽  
High Risk ◽  
Diagnostic Criteria ◽  
Body Mass ◽  
Cox Regression ◽  
Risk Groups ◽  
World Health ◽  
Obese People ◽  
Cox Regression Analysis ◽  
Health Organization

Abstract Background Triglyceride glucose-body mass index (TyG-BMI) has been recommended as an alternative indicator of insulin resistance. However, the association between TyG-BMI and pre-diabetes remains to be elucidated. Methods More than 100,000 subjects with normal glucose at baseline received follow-up. The main outcome event of concern was pre-diabetes defined according to the diagnostic criteria recommended by the American Diabetes Association (ADA) in 2018 and the World Health Organization (WHO) in 1999. A Cox proportional hazard regression model was used to evaluate the role of TyG-BMI in identifying people at high risk of pre-diabetes. Results At a mean observation period of 3.1 years, the incidence of pre-diabetes in the cohort was 3.70 and 12.31% according to the WHO and ADA diagnostic criteria for pre-diabetes, respectively. The multivariate Cox regression analysis demonstrated that TyG-BMI was independently positively correlated with pre-diabetes, and there was a special population dependence phenomenon. Among them, non-obese people, women and people under 50 years old had a significantly higher risk of TyG-BMI-related pre-diabetes (P-interaction< 0.05). Conclusions These findings suggest that a higher TyG-BMI significantly increases an individual’s risk of pre-diabetes, and this risk is significantly higher in women, non-obese individuals, and individuals younger than 50 years of age.

scholarly journals The Expression of miR-155-5p and Local Matrix Gla Protein in Meningiomas

2021 ◽  
Vol 29 (3) ◽  
pp. 299-306
Author(s):  
Simona Roxana Gheorghe ◽  
Cătălin Marian ◽  
Ligia Gabriela Tătăranu ◽  
Anica Dricu ◽  
Cees Vermeer ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Molecular Classification ◽  
Micro Rna ◽  
Matrix Gla Protein ◽  
World Health ◽  
Ectopic Calcification ◽  
Chain Reaction ◽  
The World ◽  
Polymerase Chain ◽  
Health Organization

Abstract Meningiomas are classified by the World Health Organization (WHO) in three grades, based on morphological features. Independent of this grading, the presence of calcification in meningiomas influences their growth rate. The messenger RNA of matrix Gla protein (MGP), an extra-hepatic protein with different conformations involved in the homeostasis of ectopic calcification has been found in meningiomas and was shown to be regulated in breast cancer by miR-155-5p, a specific micro RNA. Therefore, we investigated the expression of miR-155-5p and its relationship with local MGP conformations in different grade meningiomas. According to the WHO classification, our 41 samples of meningiomas were stratified in groups WHO I and WHO II. Using real time polymerase chain reaction, we observed a higher miR-155-5p expression in group WHO I versus group WHO II [with a fold change (FC) of 3.83, p=0.027)]. Moreover, the expression of miR-155-5p was higher in calcified tumors compared to non-calcified tumors in all samples (FC=3.01, p=0.047) and in group WHO I (FC=3.65, p=0.048). Utilizing immunohistochemistry, we determined the concurrent presence of all MGP conformations in calcified meningiomas. This study was the first to establish higher miR-155-5p expression in grade WHO I and calcified meningiomas, which could improve molecular classification and targeted therapy and also the presence of all MGP conformations in calcified meningiomas, confirming the existence of an anti-calcification mechanism in meningiomas..

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