Evaluating the clinical feasibility: The direct bisulfite genomic sequencing for examination of methylated status of protocadherin10 (PCDH10) promoter to predict the prognosis of gastric cancer
Affiliations: Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China
Correspondence:
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Corresponding authors: Han Liang and Jing-Yu Deng, Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China. E-mail:tjlianghan@sohu.com/dengery@126.com
Abstract:
OBJECTIVE: To elucidate the clinical significance of the methylated
status of CpG site count of PCDH10 promoter in the survival prediction in
gastric cancer (GC). METHODS: In the previous study, we demonstrated that the methylated
CpG site count was significantly associated with the overall survival (OS)
of GC patients by using the bisulfite genomic sequencing (BGS) with no less
than five clones per sample. It was so complex and expensive for patients to
undergo the BGS clones. In this study, we detected the different CpG site
counts (hypermethylated and hypomethylated) of PCDH10 DNA promoter in GC
samples of 471 patients by directly bisulfite genomic sequencing (D-BGS)
without any clone. Furthermore, we evaluated the relationships between the
methylated status of PCDH10 promoter and OS. RESULTS: Two hundred and fifty-seven of 471 (54.6%) GC patients were identified to
present with PCDH10 promoter methylation by D-BGS. Patients who presented
with 5 or more methylated CpG site counts of PCDH10 promoter had
significantly poorer prognosis than patients who with less than 5 methylated
CpG site counts of PCDH10 promoter (p= 0.039). With the multivariate survival
analysis, we demonstrated that T stage, N stage and the hypermethylated CpG
site counts of PCDH10 DNA promoter were the independent predictors of OS of
GC patients. In addition, the hypermethylated CpG site counts of PCDH10 DNA
promoter had smaller Akaike information criterion (AIC) and Bayesian
information criterion (BIC) values than the other two independent predictors
of the OS, indicating the hypermethylated CpG site counts of PCDH10 DNA
promoter as the best prognostic predictor of GC. CONCLUSIONS: Our present findings suggested that the
hypermethylated CpG site counts of PCDH10 DNA promoter for evaluating the
prognosis of GC was reasonable by using the D-BGS.
Keywords: PCDH10, methylation, direct bisulfite genomic sequencing, prognosis, gastric cancer
