ISSN: 1449-2288International Journal of Biological Sciences
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Int J Biol Sci 2015; 11(1):88-98. doi:10.7150/ijbs.10583 This issue Cite
Research Paper
Integrative Genomic and Transcriptomic Characterization of Matched Primary and Metastatic Liver and Colorectal Carcinoma
1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, MD, USA;
2. Liver Cancer Institute, Fudan University, Shanghai, China;
3. Laboratory of Cancer Biology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA;
4. Laboratory of Molecular Technology, NCI-Frederick, SAIC-Frederick, Frederick, MD 21701, USA;
5. Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
* These authors contributed equally to this work.
# Current address: SR, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; GL, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Abstract
Metastasis is the main cause of cancer mortality but its process remains poorly understood and thus hampers more effective treatment and improved cancer prognosis. To search for metastasis driver genes responsible for tumor spread, we integrated genomic and transcriptomic profiles of 61 matched primary tumors and distant metastases of liver or colorectal carcinoma isolated by laser-capture microdissection and assayed by array-based technologies. We found that primary tumor lesions and their matched distant metastases were largely similar at the genomic and transcriptomic levels, but substantial differences could be found between primary tumors with or without accompanying metastases. Interestingly, metastasis genes were principally tumor type and organ site-specific. Despite distinct pathway enrichment, different metastasis gene sets shared common prognostic capacity and were predictive of hepatocellular carcinoma survival in an independent cohort. Thus, the metastatic propensity is inherent to the primary tumor and the lack of general metastasis genes necessitates the development of specific treatment modalities.
Keywords: Liver cancer, Colon cancer, Organ site-specific metastasis, Profiling.
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