Prognostic implications and interaction of L1 methylation and p53 expression statuses in advanced gastric cancer

Clinical Epigenetics

Sun Lee¹  Woo Ho Kim²  Yun-Joo Shin³  Nam-Yun Cho³  Xianyu Wen⁴  Younghoon Kim⁴  Gyeong Hoon Kang⁴ 

[1] 0000 0001 2171 7818, grid.289247.2, Department of Pathology, College of Medicine, Kyung Hee University, Seoul, South Korea;0000 0004 0470 5905, grid.31501.36, Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Chongo-gu, 03080, Seoul, South Korea;0000 0004 0470 5905, grid.31501.36, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea;0000 0004 0470 5905, grid.31501.36, Department of Cancer Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea;0000 0004 0470 5905, grid.31501.36, Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea;0000 0004 0470 5905, grid.31501.36, Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Chongo-gu, 03080, Seoul, South Korea;

关键词: LINE-1;    Methylation;    TP53;    Prognosis;    Gastric cancer;   

DOI  :  10.1186/s13148-019-0661-x

来源: publisher

【 摘 要 】

BackgroundTP53 is frequently mutated across various tissue types of cancers. In normal cells, long interspersed nuclear element-1 (LINE-1, L1) is mostly repressed by DNA methylation in its 5′ untranslated region but is activated by DNA demethylation process during tumorigenesis. p53 is indispensable for maintaining genomic stability and plays its role in controlling genomic stability by repressing retrotransposon activity. However, it is unclear whether p53 regulates expression or methylation of L1 differently depending on the mutational status of TP53. Four hundred ninety cases of advanced gastric cancer (AGC) were analyzed for their statuses in p53 expression and L1 methylation using immunohistochemistry and pyrosequencing, respectively. Whether L1 methylation and expression statuses were differently affected by types of TP53 mutants was analyzed in gastric cancer cell line.ResultsBy p53 immunohistochemistry, tumors were classified into 4 groups according to the intensity and extent of stained tumor nuclei. L1 methylation level was significantly higher in p53 expression group 1 than in the other groups in which L1 methylation level was similar (P <  0.001). Although L1 methylation and p53 expression statuses were associated with patient survival, multivariate analysis revealed that L1 methylation was an independent prognostic parameter. In in vitro analysis of AGS cells with the introduction of wild type or mutant types of TP53, L1 methylation level and activity were different depending on types of TP53 mutation.ConclusionsFindings suggest that L1 methylation level is affected by TP53 mutation status; although, L1 methylation status was an independent prognostic parameter in patients with AGC. Further study is required to elucidate the mechanism of how wild type or mutant p53 affects L1 activity and methylation status of L1 CpG island.

【 授权许可】

CC BY