DNA Methylation Biomarkers and Metastasis of Gastric Carcinoma

NCT02159339 | Completed DMC

• 1 other identifier: Methylation-14414
• Study Type: observational
• Target: 198
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Carcinoma

Keywords

DNA methylation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Disease-free (Recurrence/metastasis-free) survival (DFS) and overall survival (OS) of patients with gastric carcinoma after surgical resection

  from 4 months to 144 months

Study Arms (1)

gene-methylation

gene-low-level of methylation: patients with early stage gastric carcinoma containing low-level of methylation change of E-cadherin,GFRA1,p16,SRF and ZNF382 CpG island. gene-middle-level of methylation: patients with early stage gastric carcinoma containing middle-level of methylation change of E-cadherin,GFRA1,p16,SRF and ZNF382 CpG island. gene-high-level of methylation: patients with early stage gastric carcinoma containing high-level of methylation change of E-cadherin,GFRA1,p16,SRF and ZNF382 CpG island. gene-without of methylation: patients with early stage gastric carcinoma NOT containing methylated E-cadherin,GFRA1,p16,SRF or ZNF382 CpG island.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

198 early stage gastric carcinoma (GC) inpatients that underwent surgical treatment at Peking University Cancer Hospital \& Institute between 2002 and 2012 were enrolled in the cohort. All of the enrolled patients had been diagnosed pathologically by senior pathologists. The 2010 UICC-TNM (tumor-node-metastasis) system was used for the classification of GCs. All cases involved primary lesions without neoadjuvant chemotherapy. Genes methylation status of GC samples was analyzed with MethyLight combined with denatured high performance liquid chromatography. 191 eligible cases with gene-methylated or gene-methylated GC were enrolled into the cohort study.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead
• Peking University: collaborator

Study Sites (1)

Beijing Cancer Hospital & Institute

Beijing, Beijing Municipality, 100000, China

Location

Related Publications (2)

• 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-09-0580. Epub 2009 Aug 11.

  PMID: 19671846 RESULT

• Liu Z, Cheng X, Zhang L, Zhou J, Deng D, Ji J. A panel of DNA methylated markers predicts metastasis of pN0M0 gastric carcinoma: a prospective cohort study. Br J Cancer. 2019 Oct;121(7):529-536. doi: 10.1038/s41416-019-0552-0. Epub 2019 Aug 21.

  PMID: 31431673 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Tissue specimens are surgically collected from inpatients with pN0M0-stage gastric carcinoma. Genomic DNA sample is extracted from tissues. Unmethylated cytosine residues in DNA are converted into uracil residues with bisulfite modification.

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• Dajun Deng, Master

  Peking University Cancer Hospital & Institute

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Zhaojun Liu

Study Record Dates

• First Submitted: June 6, 2014
• First Posted: June 9, 2014
• Study Start: December 1, 2012
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: June 19, 2015

Record last verified: 2015-06

Locations

CN (1)