Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of E3 ubiquitin ligase RNF180 DNA promoter to predict the survival of gastric cancer
Affiliations: [a] Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China | [b] Central Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
Correspondence:
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Corresponding authors: Han Liang, Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Tel.: +86 22 23340123;
Fax: +86 22 23359904; E-mail: tjlianghan@sohu.com; Jing-Yu Deng, Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China. Tel.: +86 22 23340123; Fax: +86 22 23359904; E-mail: dengery@126.com
Abstract:
BACKGROUND: E3 ubiquitin ligase Ring finger protein 180 (RNF180)
has been identified as a novel tumor suppressor in gastric cancer and the
methylated CpG site count of RNF180 DNA promoter can predict the prognosis
for gastric cancer patients. OBJECTIVE: In the previous study, we demonstrated that methylated
CpG site count of RNF180 DNA promoter was significantly associated with the
survival of patients with gastric cancer using the bisulfite genomic
sequencing (BGS) in the gastric cancer tissue with five clones per sample.
It was so complicate for each patient underwent the BGS detection with
clones. It is important to explore a simple, rapid and accurate method to
detect methylated CpG site count to predicting the prognosis for gastric
cancer patients. METHODS: At present study, we detected
hypermethylated and hypomethylated CpG site count of RNF180 DNA promoter in
samples of 480 gastric cancer patients by direct bisulfite sequencing. RESULTS: We found that patients who possessed seven or less
hypermethylated CpG sites of RNF180 DNA promoter had much better survival
(p= 0.008), which was similar to our previous research results by using the
BGS with clones. With the multivariate survival analysis, we found that T
stage, N stage and hypermethylated CpG site count of RNF180 DNA promoter
were the independent predictors of prognosis for gastric cancer patients. CONCLUSIONS: hypermethylated CpG site count of RNF180 DNA promoter
for evaluating the prognosis of gastric cancer was reasonable by using the
direct bisulfite sequencing.
Keywords: Ring finger protein 180, methylation, direct bisulfite genomic sequencing, prognosis, gastric cancer
