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...
Main Authors: | , , , , , , , |
---|---|
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 |
_version_ | 1828729032859975680 |
---|---|
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. |
first_indexed | 2024-04-12T14:25:47Z |
format | Article |
id | doaj.art-f2422cbd6d574f37a2f0058674ca64e0 |
institution | Directory Open Access Journal |
issn | 2234-943X |
language | English |
last_indexed | 2024-04-12T14:25:47Z |
publishDate | 2022-06-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Oncology |
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 |
work_keys_str_mv | AT miaolongyan thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT miaolongyan thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT jiayuanwu thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT minxue thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT minxue thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT juanfenmo thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT lizheng thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT junzhang thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT zhenzhengao thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT yibao thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT yibao thestudiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT miaolongyan studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT miaolongyan studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT jiayuanwu studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT minxue studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT minxue studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT juanfenmo studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT lizheng studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT junzhang studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT zhenzhengao studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT yibao studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors AT yibao studiesofprognosticfactorsandthegeneticpolymorphismofmethylenetetrahydrofolatereductasec667tinthymicepithelialtumors |