DNA Methylation Biomarkers and Metastasis of Gastric Carcinoma
A Cohort Study on Prediction of Metastasis of Gastric Carcinoma by DNA Methylation Biomarkers
調査の概要
状態
条件
詳細な説明
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.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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Beijing
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Beijing、Beijing、中国、100000
- Beijing Cancer Hospital & Institute
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
- 高齢者
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：コホート
- 時間の展望：見込みのある
コホートと介入
グループ/コホート |
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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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Metastasis and/ or recurrence of gastric carcinoma
時間枠：3 years
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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.
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3 years
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Disease-free (Recurrence/metastasis-free) survival (DFS) and overall survival (OS) of patients with gastric carcinoma after surgical resection
時間枠：from 4 months to 144 months
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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
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from 4 months to 144 months
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協力者と研究者
捜査官
- スタディディレクター：Dajun Deng, Master、Peking University Cancer Hospital & Institute
出版物と役立つリンク
一般刊行物
- 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.
- 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.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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