Abstract 175P
Background
Helicobacter pylori-induced aberrant JAK/STAT3 signaling contributed to the development of gastric cancer. We hypothesize that activated STAT3 may epigenetically repress it’s targets by DNA methylation. The object of this study is to identified the diagnostic and prognostic value of novel STAT3 targets that are hypermethylated in gastric cancer.
Methods
Fifty patients’ clinical data and genomic DNA were collected from the Changhua Christian Hospital, Taiwan. DNA methylation microarray was used to analyze the methylation status in AGS gastric cancer cells and patient samples with different STAT3 status. Bioinformatic analyses was carried out to identify STAT3 targets with differential methylation status. Bisulphite pyrosequencing was designed and performed in cancer and normal tissue to examine the methylation level of the target genes. Receiver operating character (ROC) curve and the survival analysis were examined.
Results
We found that promoter hypomethylation of PCDHB15, a potential STAT3 target, was observed in AGS cells depleted with STAT3, while promoter hypermethylation was observed in patient samples with activated STAT3. Cell line studies found that treatment with the DNMT inhibitor, 5azaDC, restored PCDHB15 expression in AGS. Pyrosequencing in various cell lines, including AGS, MKN28, MKN45, SNU1 and SNU16, demonstrated hypermethylation of the PCDHB15 promoter. Compared to the cancer tissue, a lower PCDHB15 methylation was observed in matched adjacent tissue (P = 0.001) and gastritis tissue (P < 0.001). Interestingly, Kaplain-Meier analysis found that patients with higher PCDHB15 methylation had longer survival as compared to patients with lower methylation (p = 0.03).
Conclusions
Our study indicate that methylated PCDHB15 promoter may be associated with development of gastric cancer. Patients with higher PCDHB15 methylation are prone to have better prognosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This study was supported by a grant from Taichung Veterans General Hospital (RVHYCY-107008).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
97P - The role of adjuvant chemotherapy according to the status of surgical margin in rectal cancer
Presenter: Jong Hoon Lee
Session: Poster display session
Resources:
Abstract
98P - Influence of DPYD*9, DPYD*6 and GSTP1 ile105val genetic polymorphisms on capecitabine and oxaliplatin (CAPOX) associated toxicities in colorectal cancer patients
Presenter: Ashok Varma
Session: Poster display session
Resources:
Abstract
99P - Patient-derived tumour model by new culture method leading to the precision medicine
Presenter: Norikatsu Miyoshi
Session: Poster display session
Resources:
Abstract
100P - Clinical impact and carcinogenic mechanism of NCAPG overexpression in colon cancer
Presenter: Kai-Yuan Lin
Session: Poster display session
Resources:
Abstract
101P - Combined cellular immunotherapy and chemotherapy improves clinical outcome and displays safety in the treatment of patients with colorectal cancer
Presenter: Chang Wang
Session: Poster display session
Resources:
Abstract
102P - Clinical features of anorectal cancer in patients with Crohn’s disease: Japanese single center study
Presenter: Kazuhiro Watanabe
Session: Poster display session
Resources:
Abstract
103P - Contrast-enhanced CT-based textural parameters as potential prognostic factors of survival for colorectal cancer patients receiving targeted therapy
Presenter: Yanfei Yang
Session: Poster display session
Resources:
Abstract
104P - Prognostic significance of tumour location to the oncologic outcome of colon cancer
Presenter: Sare Hosseini
Session: Poster display session
Resources:
Abstract
105P - Detection and clinical significance of circulating tumour cells in patients with rectal cancer
Presenter: Shuohui Dong
Session: Poster display session
Resources:
Abstract
106P - The risk of malignization incidence in patients with polyps and polyposis of the colon and rectum
Presenter: Yakov Ten
Session: Poster display session
Resources:
Abstract