| Project Title: | Discovery of biomarkers for gastric cancer | |
| Cancer Site: | Stomach | |
| Principal Investigator(s): |
|
|
| Participating Institutions: |
Agency For Science, Technology and Research (A*STAR – Co-Lead Institution)
National University of Singapore (NUS – Co-Lead Institution) Genome Institute of Singapore (GIS) Institute of Molecular and Cell Biology (IMCB) Bioinformatics Institute |
|
| Mouse Model(s): | TBA | |
| Technical Approaches: |
Proteomics Platform:
2D-difference gel electrophoresis (2D-DIGE) Isobaric tags for absolute and relative quantification (iTRAQ) Isotope-coded affinity tagging (ICAT) Mass spectrometry Sample pre-fractionation including glycoprotein and DNA binding protein enrichment Serological screening of tumor antigens using autoantibodies from autologous patient sera Subcellular proteomics including plasma membrane and mitochondria enrichment Genomics Platform: Chromatin immunoprecipitation pair-end tag sequencing (ChIP-PET) Gene identification signature (GIS) analysis |
|
Gastric adenocarcinoma is the second leading cause of cancer death worldwide. It is particularly common in Asia and especially in China and Japan. In Singapore it is the fourth most common cancer in males who have a 1:50 lifetime risk of developing gastric cancer. Gastric cancer traditionally carries a poor prognosis with 79% of tumors diagnosed at stage IV and five year survival less than 5%. Advanced gastric cancer is generally refractory to chemotherapy, which leads to poor prognosis. It has been shown that if it is diagnosed at an early stage, it is a curable disease. Therefore it is most important to be able to identify clinically useful early markers that can detect gastric cancer at an early stage.
The Gastric Cancer Epidemiology and Genetics Programme (GCEP), a research program which aims to identify clinical and genetic biomarkers for gastric cancer, initiated the GCEP Cohort Study for subjects at high risk of gastric cancer in January 2004. People aged >50 years who are at high risk for gastric cancer will be offered screening by endoscopy with careful and systematic follow-up over a minimum of 5 years. An enrollment of 4000 subjects over 5 years is planned with 202 subjects already prospectively recruited since 2004. Specimens collected for this Cohort Study to be used for biomarker discovery will include gastric mucosal biopsies, sera, gastric juice, leucocyte DNA and RNA, and a culture of Helicobacter pylori, a gastric pathogen bacterium strongly associated with gastric cancer.
The proteomics platform for biomarker discovery will include the following strategies:
The cancer genomics platform for biomarker discovery will employ two main technologies to identify genetic changes associated with gastric cancer. Gene Identification Signature (GIS) analysis will be used to annotate all key translocations and abnormal transcripts in primary gastric cancers. In addition, a novel and powerful technology called chromatin immunoprecipitation pair-end tag sequencing (ChIP-PET) will be used to identify all binding sites of the RUNX3 nuclear oncogene which has been found to be directly involved in gastric cancer development, and of p53 which has been implicated in the progression of gastric cancers.
Max CHUNG, Ph.D. (NUS) [bchcm@nus.edu.sg] (bio)
Yoshiaki ITO, M.D., Ph.D. (NUS; IMCB) [itoy@imcb.a-star.edu.sg] (bio)
David LANE, Ph.D. (IMCB) (Biomarker Team PI) [d.p.lane@imcb.a-star.edu.sg] (bio)
Hew Choy LEONG, Ph.D. (NUS) [dbshead@nus.edu.sg] (bio)
Qinsong LIN, Ph.D. (NUS) [dbslinqs@nus.edu.sg] (bio)
Edison LIU, M.D. (GIS; NUS) [liue@gis.a-star.edu.sg] (bio)
JJ LIU, Ph.D. (GIS; NUS) [liuj3@gis.a-star.edu.sg] (bio)
Lance MILLER, Ph.D. (GIS) [millerl@gis.a-star.edu.sg] (bio)
Nallasivam PALANISAMY, Ph.D. (GIS) [palanisamyn@gis.a-star.edu.sg] (bio)
Gunaretnam RAJAGOPAL, Ph.D. (Bioinformatics Institute, Singapore) [guna@bii.a-star.edu.sg] (bio)
Yijun RUAN, Ph.D. (GIS) [ruanyj@gis.a-star.edu.sg] (bio)
Mark SEIELSTAD, Ph.D. (GIS; NUS) [seielstadm@gis.a-star.edu.sg] (bio)
Chialin WEI, Ph.D. (GIS) [weicl@gis.a-star.edu.sg] (bio)
K.G. YEOH, MBBS, M.Med. (NUS) (Biomarker Team Co-PI) [mdcykg@nus.edu.sg] (bio)
 | |
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |
