Clinical trial NCT02159339: DNA Methylation Biomarkers and Metastasis of Gastric Carcinoma
Official title: A Cohort Study on Prediction of Metastasis of Gastric Carcinoma by DNA Methylation Biomarkers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Gastric Carcinoma
Keywords: DNA methylation
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
Collaborators: name: Peking University
First posted: 2014-06-09
Enrollment: 198
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Metastasis and/ or recurrence of gastric carcinoma
timeFrame: 3 years
Secondary outcomes:
measure: Disease-free (Recurrence/metastasis-free) survival (DFS) and overall survival (OS) of patients with gastric carcinoma after surgical resection
timeFrame: from 4 months to 144 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital & Institute
state: Beijing
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Dajun Deng, Master
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.