The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors

ObjectiveTo describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of T...

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Main Authors: Miaolong Yan, Jiayuan Wu, Min Xue, Juanfen Mo, Li Zheng, Jun Zhang, Zhenzhen Gao, Yi Bao
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.847957/full
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author Miaolong Yan
Miaolong Yan
Jiayuan Wu
Min Xue
Min Xue
Juanfen Mo
Li Zheng
Jun Zhang
Zhenzhen Gao
Yi Bao
Yi Bao
author_facet Miaolong Yan
Miaolong Yan
Jiayuan Wu
Min Xue
Min Xue
Juanfen Mo
Li Zheng
Jun Zhang
Zhenzhen Gao
Yi Bao
Yi Bao
author_sort Miaolong Yan
collection DOAJ
description ObjectiveTo describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of TETs.MethodsPathological records were reviewed from the database of the Second Affiliated Hospital of Jiaxing University, from January 2010 to December 2020, and 84 patients with TETs were recruited for this study. Univariate and multivariate analyses were performed to determine the prognostic factors. The genetic polymorphism of MTHFR C667T was examined in the patients with TETs and in a group of healthy individuals. The correlation between MTHFR transcriptional levels and methylation was analyzed using The Cancer Genome Atlas (TCGA) thymoma dataset from the cBioPortal platform.ResultsKaplan–Meier univariate survival analysis showed that sex, age, the maximum tumor diameter, surgery, chemotherapy, radiotherapy, WHO histological classification, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging, were statistically significantly correlated with the prognosis of patients with TETs. The Masaoka–Koga stage and 8th UICC/AJCC TNM staging were strongly correlated with each other in this study (r=0.925, P<0.001). Cox multivariate survival analysis showed that the maximum tumor diameter, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging were independent prognostic factors affecting the overall survival (OS) of patients with TETs (P<0.05). The MTHFR C667T genotype (χ2 = 7.987, P=0.018) and allele distribution (χ2 = 5.750, P=0.016) were significantly different between the patients and healthy controls. CT heterozygous and TT homozygous genotypes at this MTHFR polymorphism significantly increased the risk of TETs (odds ratio [OR] =4.721, P=0.008). Kaplan–Meier univariate survival analysis showed that there was no correlation between different genotypes and the prognosis of TETs (CC versus CT + TT, χ2 =0.003, P=0.959). Finally, a negative correlation between the transcriptional and methylation levels of MTHFR was observed in the TCGA thymoma dataset (r=-0.24, P=0.010).ConclusionsThe Masaoka–Koga stage, 8th UICC/AJCC TNM staging, and maximum tumor diameter were independent prognostic factors for TETs. Reduced methylation levels of MTHFR and particular polymorphic variants may contribute to the susceptibility to developing TETs.
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spelling doaj.art-f2422cbd6d574f37a2f0058674ca64e02022-12-22T03:29:27ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.847957847957The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial TumorsMiaolong Yan0Miaolong Yan1Jiayuan Wu2Min Xue3Min Xue4Juanfen Mo5Li Zheng6Jun Zhang7Zhenzhen Gao8Yi Bao9Yi Bao10The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaThe Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaGraduate School, Bengbu Medical College, Bengbu, ChinaThe Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Department of Thoracic Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaThe Department of Oncology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, ChinaObjectiveTo describe the clinical features of a cohort of patients with thymic epithelial tumors (TETs) and to analyze their prognostic factors. In particular, we investigated the correlation between the genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) C667T and the incidence of TETs.MethodsPathological records were reviewed from the database of the Second Affiliated Hospital of Jiaxing University, from January 2010 to December 2020, and 84 patients with TETs were recruited for this study. Univariate and multivariate analyses were performed to determine the prognostic factors. The genetic polymorphism of MTHFR C667T was examined in the patients with TETs and in a group of healthy individuals. The correlation between MTHFR transcriptional levels and methylation was analyzed using The Cancer Genome Atlas (TCGA) thymoma dataset from the cBioPortal platform.ResultsKaplan–Meier univariate survival analysis showed that sex, age, the maximum tumor diameter, surgery, chemotherapy, radiotherapy, WHO histological classification, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging, were statistically significantly correlated with the prognosis of patients with TETs. The Masaoka–Koga stage and 8th UICC/AJCC TNM staging were strongly correlated with each other in this study (r=0.925, P<0.001). Cox multivariate survival analysis showed that the maximum tumor diameter, Masaoka–Koga stage, and 8th UICC/AJCC TNM staging were independent prognostic factors affecting the overall survival (OS) of patients with TETs (P<0.05). The MTHFR C667T genotype (χ2 = 7.987, P=0.018) and allele distribution (χ2 = 5.750, P=0.016) were significantly different between the patients and healthy controls. CT heterozygous and TT homozygous genotypes at this MTHFR polymorphism significantly increased the risk of TETs (odds ratio [OR] =4.721, P=0.008). Kaplan–Meier univariate survival analysis showed that there was no correlation between different genotypes and the prognosis of TETs (CC versus CT + TT, χ2 =0.003, P=0.959). Finally, a negative correlation between the transcriptional and methylation levels of MTHFR was observed in the TCGA thymoma dataset (r=-0.24, P=0.010).ConclusionsThe Masaoka–Koga stage, 8th UICC/AJCC TNM staging, and maximum tumor diameter were independent prognostic factors for TETs. Reduced methylation levels of MTHFR and particular polymorphic variants may contribute to the susceptibility to developing TETs.https://www.frontiersin.org/articles/10.3389/fonc.2022.847957/fullthymic epithelial tumorsMasaoka–Koga Stage8th UICC/AJCC TNM stagingMTHFR polymorphismmethylation
spellingShingle Miaolong Yan
Miaolong Yan
Jiayuan Wu
Min Xue
Min Xue
Juanfen Mo
Li Zheng
Jun Zhang
Zhenzhen Gao
Yi Bao
Yi Bao
The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
Frontiers in Oncology
thymic epithelial tumors
Masaoka–Koga Stage
8th UICC/AJCC TNM staging
MTHFR polymorphism
methylation
title The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
title_full The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
title_fullStr The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
title_full_unstemmed The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
title_short The Studies of Prognostic Factors and the Genetic Polymorphism of Methylenetetrahydrofolate Reductase C667T in Thymic Epithelial Tumors
title_sort studies of prognostic factors and the genetic polymorphism of methylenetetrahydrofolate reductase c667t in thymic epithelial tumors
topic thymic epithelial tumors
Masaoka–Koga Stage
8th UICC/AJCC TNM staging
MTHFR polymorphism
methylation
url https://www.frontiersin.org/articles/10.3389/fonc.2022.847957/full
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