DNA Methylation Biomarkers and Metastasis of Gastric Carcinoma

Gastric Carcinoma Clinical Trial

Official title:

A Cohort Study on Prediction of Metastasis of Gastric Carcinoma by DNA Methylation Biomarkers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02159339
• Other study ID #: Methylation-14414
• Status: Completed
• Phase: N/A
• First received: June 6, 2014
• Last updated: June 17, 2015
• Start date: December 2012
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: Beijing Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Gastric carcinoma (GC) is the second leading cause of cancer death throughout the world. In previous multi-center study, we have found that the prevalence of GDNF family receptor alpha 1(GFRA1), serum response factor (SRF), and ZNF382 methylation alterations were inversely and coordinately associated with GC metastasis and the patients' overall survival throughout discovery and testing cohorts in China, Japan and Korea. The present cohort study is to investigate whether methylation of those genes can predict the metastasis and prognosis of GC.

Description:

Background: Metastasis is the leading cause of death for gastric carcinoma (GC). Currently, GC prognosis is primarily determined based on the clinical data and pathological stages of patients at the time of diagnosis and treatment. However, successful management of GC patients is still hampered by lack of highly sensitive and specific biomarkers capable of predicting prognosis and likelihood of metastasis. GFRA1 hypomethylation along with SRF and ZNF382 hypermethylation were found to be potential synergistic biomarkers for the prediction of GC metastasis in our previous multi-center study. In addition, p16 and E-cadherin were also correlated with GC metastasis in Chinese cohort. To investigate the predictive value of those genes' methylation on metastasis potential in GC, we carried out the prospective cohort study.

Methods: 198 early stage GC patients without lymph node or distal metastasis were included in the present study. Baseline information of E-cadherin, GFRA1, p16, SRF and ZNF382 methylation status of the GC from 191 cases was obtained by MethyLight. The follow-up examination was carried out in a double-blind study with a 6-month interval. The association between gene methylation and metastasis of GC was analyzed with SPSS16.0 software. All P-values were two-sided.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 198
• Est. completion date: June 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Histological diagnosis of gastric adenocarcinoma;

• Early stage GC without lymph node and distal metastasis;

• Availability of frozen, fresh GC and corresponding surgical margin samples;

• Available of methylation status of gene CpG island in the extracted DNA sample.

Exclusion Criteria:

• GC with lymph node or distal metastasis;

• Quality of the prepared DNA is not good enough for detection of gene methylation;

• GC cases were subjected to the neoadjuvant chemotherapy.

Related Conditions & MeSH terms

• Carcinoma
• Gastric Carcinoma
• Stomach Neoplasms

Locations

Country	Name	City	State
China	Beijing Cancer Hospital & Institute	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Cancer Hospital	Peking University

Country where clinical trial is conducted

China, 

References & Publications (1)

Cao J, Zhou J, Gao Y, Gu L, Meng H, Liu H, Deng D. Methylation of p16 CpG island associated with malignant progression of oral epithelial dysplasia: a prospective cohort study. Clin Cancer Res. 2009 Aug 15;15(16):5178-83. doi: 10.1158/1078-0432.CCR-09-058 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastasis and/ or recurrence of gastric carcinoma	The hazard ratio, positive prediction value, and negative prediction value of metastasis/recurrence of gastric carcinomas are calculated according to the metastasis/recurrence frequences among patients with the different methylation status of each target gene CpG islands. These patients are classified into four groups for each gene: A) cases without methylation change; B) cases with the low-level of methylation change (33.3% of cases with methylation change); C) cases with the middle-level of methylation change (33.3% of cases with methylation change); D) cases with the high-level of methylation change (33.3% of cases with methylation change). Combination analysis will be carried out using Support Vector Classification model.	3 years
Secondary	Disease-free (Recurrence/metastasis-free) survival (DFS) and overall survival (OS) of patients with gastric carcinoma after surgical resection	The classification of patients is the same as the primary outcome measure. The log-rank test will be used to compare survival time between groups. Cox-proportional hazards models will be used to identify independent predictors of survival (month) with adjustment for relevant clinical covariates	from 4 months to 144 months