Study on the correlation between TFF1 methylation and methyltransferase SETDB1 ex-pression in lung adenocarcinoma
10.12354/j.issn.1000-8179.2025.20241521
- VernacularTitle:TFFl甲基化和甲基转移酶SETDB1表达在肺腺癌中的相关性研究
- Author:
Guo CHAO
1
;
Han XIAOLI
;
Huang JINGTAO
;
Yang YUE
;
Sun GUANGRUI
;
Liang ZONGYING
Author Information
1. 河北省保定市第二中心医院肿瘤科(河北省 保定市 072750)
- Publication Type:Journal Article
- Keywords:
lung adenocarcinoma;
TFF1 gene;
methylation;
SETDB1;
epigenetics
- From:
Chinese Journal of Clinical Oncology
2025;52(1):7-11
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the relationship between SET domain bifurcated 1(SETDB1)expression and trefoil factor 1(TFF1)gene methylation,along with its clinical significance.Methods:Fifty-five lung adenocarcinoma samples and normal tissues of distant cancer were collected from the Affiliated Hospital of Chengde Medical College Hebei Province.TFF1 gene methylation levels were measured by pyrosequencing,relative TFF1 mRNA expression was assessed using quantitative real-time polymerase chain reaction(qRT-PCR),and TFF1 and SETDB1 protein expression were quantified via immunohistochemistry.The clinical significance and correlation between TFF1 methyla-tion levels and SETDB1 protein expression were analyzed statistically.In vitro,SETDB1 siRNA or negative control siRNA was transfected into A549 cells.Following transfection,SETDB1 mRNA expression was analyzed using qRT-PCR,and SETDB1 protein expression was evaluated via Western blot.TFF1 methylation was reassessed via pyrosequencing.Results:In lung adenocarcinoma and normal tissues of distant cancer,TFF1 gene methylation rates were(70.16±6.32)%and(12.46±2.22)%,respectively.TFF1 mRNA relative expression levels were 0.56±0.17 for cancer tissues and 1.56±0.22 for the normal tissues of distant cancer.All detected differences were statistically significant(all P<0.05).TFF1 protein expression rates were 29.09%(16/55)for cancer tissues and 65.45%(36/55)for the normal tissues of distant cancer.Additionally,relative positivity rates for SETDB1 protein expression were 74.55%(41/55)and 23.64%(13/55),respectively,and all differences were stat-istically significant(all P<0.05).Western blot analysis showed that SETDB1 protein expression was significantly higher in cancer tissues(72.89±5.27)%,compared to normal tissues of distant cancer(24.27±2.37)%.In contrast,TFF1 protein expressed was markedly lower in can-cer tissues(15.38±2.33)%than in normal tissues of distant cancer(72.72±4.48)%.All differences were statistically significant(all P<0.05).TFF1 methylation and SETDB1 expression were associated with lung adenocarcinoma(r=0.486,P<0.05).Both TFF1 methylation and SETDB1 expression were closely associated with tumor TNM stage,tissue differentiation,and lymph node metastasis(P<0.05).Furthermore,TFF1 methylation increased following SETDB1 downregulation(P<0.05).Conclusions:During lung adenocarcinoma progression,SETDB1 expres-sion correlates with TFF1 methylation,and the highly expressed SETDB1 may play a role in catalyzing TFF1 methylation.
