DNA Methylation Biomarkers and Metastasis of Gastric Carcinoma

June 17, 2015 updated by: Zhaojun Liu, Peking University Cancer Hospital & Institute

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
198

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100000
        • Beijing Cancer Hospital & Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Metastasis and/ or recurrence of gastric carcinoma
Time Frame: 3 years
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Disease-free (Recurrence/metastasis-free) survival (DFS) and overall survival (OS) of patients with gastric carcinoma after surgical resection
Time Frame: from 4 months to 144 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Peking University Cancer Hospital & Institute

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Peking University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Dajun Deng, Master, Peking University Cancer Hospital & Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 6, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 9, 2014

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 19, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Methylation-14414

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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