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
51P - Enhancing the anti-breast tumour activity of STING through a novel sting transcriptional regulator
Presenter: Hanchu Xiong
Session: Poster display session
Resources:
Abstract
52P - Reverse Warburg effect-related mitochondrial activity and 18F-FDG uptake in invasive ductal carcinoma
Presenter: Byung Wook Choi
Session: Poster display session
Resources:
Abstract
53P - Phase II study of atorvastatin in combination with radiotherapy and temozolomide in patients with glioblastoma (ART): Final analysis report
Presenter: Abdullah Altwairgi
Session: Poster display session
Resources:
Abstract
54P - Association between Parkinson’s disease and brain tumours: A nationwide population-based cohort study
Presenter: Joo-hyun Park
Session: Poster display session
Resources:
Abstract
55P - Toxicity profiles of treatment with modern fractionated radiotherapy, contemporary stereotactic radiosurgery, or transsphenoidal surgery in non-functioning pituitary macroadenoma
Presenter: Kevin Sheng-Po Yuan
Session: Poster display session
Resources:
Abstract
56P - Hippocampal avoidance in WBRT for metastases: Comparative neurocognitive and dosimetric assessment
Presenter: Vibhay Pareek
Session: Poster display session
Resources:
Abstract
57P - Multidisciplinary brain metastasis clinic: Is it effective and worthwhile?
Presenter: Annu Rajpurohit
Session: Poster display session
Resources:
Abstract
58P - Functional status as a determinant prognostic factor for overall survival in adult patients with medulloblastoma treated with chemotherapy and radiotherapy
Presenter: Juan Ayala Alvarez
Session: Poster display session
Resources:
Abstract
59P - Pattern of care in high-grade gliomas after recurrence
Presenter: Nandini Menon
Session: Poster display session
Resources:
Abstract
60P - Five fractions plus “SRS” boost combined with temozolamide for newly diagnosed and recurrent glioblastoma multiforme (GBM)
Presenter: Azhar Rashid
Session: Poster display session
Resources:
Abstract