Gastric CarcinomaNCT02159339
DNA Methylation Biomarkers and Metastasis of Gastric Carcinoma
An observational study of Gastric Carcinoma, run by Peking University Cancer Hospital & Institute at 1 site in China.
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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Gastric Carcinoma
- How many people
- 198 participants
- Where
- 1 siteChina
- Study dates
- Dec 2012to Jun 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Beijing Cancer Hospital & Institute
Beijing, Beijing Municipality, 100000
About this study
Official title: 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.
Read the 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.
- Conditions
- Gastric Carcinoma
- Keywords
- DNA methylation
- Medical subject headings
- Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (1)
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
Measured: from 4 months to 144 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2014 (estimated)
- Study startDec 2012
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Gastric CarcinomaStudies of the same condition, open and under way.
- More trials run by Peking University Cancer Hospital & InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 198 participants (actual)
Sponsor and investigators
- Lead sponsor
- Peking University Cancer Hospital & Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University
- Responsible party
- Principal investigator, Zhaojun Liu, Peking University Cancer Hospital & Institute
- Investigators
- Dajun Deng, Master, Study director, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02159339
- Sponsor's protocol ID
- Methylation-14414
- Status last verified
- Jun 2015
- First submitted
- 6 Jun 2014
- Last updated
- 19 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19671846Liu 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.
PubMed 31431673
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cohort Study on Prediction of Metastasis of Gastric Carcinoma by DNA Methylation Biomarkers
- ClinicalTrials.gov ID
- NCT02159339
- Acronym / sponsor ID
- Methylation-14414
- Conditions
- Gastric Carcinoma
- Keywords
- DNA methylation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 198 participants (actual)
- Lead sponsor
- Peking University Cancer Hospital & InstituteUniversity, hospital or other
- Collaborators
- Peking University
- Study start
- Dec 2012
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 9 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2015.
- Results publication: PubMed 19671846Cao 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.
- Derived from this study: PubMed 31431673Liu 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dajun Deng, Master study director
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Gastric Carcinoma, run by Peking University Cancer Hospital & Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metastasis and/ or recurrence of gastric carcinoma (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02159339, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2015.