Page 75 - ebook HCC

72 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 73
FEBRUARY 13 - 16, 2014

INTEGRATIVE GENOMIC AND TRANSCRIPTOMIC
ANALYSIS TO SEARCH FOR METASTASIS
DRIVER GENES

Stephanie Roessler , Guoling Lin , Marshonna Forgues , Anuradha Budhu , Shelley Results: Analysis of the gene expression and SCNA profiles revealed that primary
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Hoover , R. Mark Simpson , Xiaolin Wu , Ping He , Lun-Xiu Qin , Zhao-You Tang , tumor and paired metastatic tissues of liver and colorectal carcinoma are very similar.
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Qing-Hai Ye , Xin Wei Wang 2 However, class comparison of non-metastatic liver cancer to lung metastases, lymph node
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1 Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany, Laboratory metastases and colorectal liver metastases resulted in 280, 730 and 1387 differential
of Human Carcinogenesis, Laboratory of Cancer Biology and Genetics, NCI, Bethesda, genes, respectively (p<0.001). The identified differential gene sets exhibited a small
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MD, USA, Laboratory of Molecular Technology, NCI, Frederick, FDA, Bethesda, MD, overlap of only 14 genes, suggesting that most genes are tumor type and organ site-
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United States, Liver Cancer Institute, Fudan University, Shanghai, China specific. Further analyses of SCNAs showed that the gene expression profiles of primary
tumors and metastasis are more stable than SCNA. Interestingly, the number of genomic
Corresponding author’s e-mail: Stephanie.Roessler@med.uni-heidelberg.de aberrations of primary versus metastatic tissue was significantly higher in liver cancer
than in colorectal cancer. The correlation of gene expression and SCNA showed that
BASIC SPEAKERS ABSTRACTS Introduction: Metastasis is the main cause of cancer mortality but its process remains metastasis genes are involved in the HMG-CoA pathway, whereas, lung metastasis genes BASIC SPEAKERS ABSTRACTS
29% of genes exhibit significant correlation. Pathway analysis showed that lymph node
are enriched in cell-cell signaling and colon metastasis in stearate/fatty acid activation.
poorly understood and thus hampers more effective treatment and improved cancer
prognosis. Thus, it is expected that there is a significant difference in tumor biology
Despite distinct pathway enrichment, different metastasis gene sets shared common
between primary tumor cells and their metastasized progenies.
prognostic capacity and were predictive of patient outcome in an independent HCC cohort
(N=242).
Aims: Identification of metastasis-related and organ site-specific metastasis genes.
implies that metastasis does not necessitate the cancer cells to acquire additional
Methodology: Here, we recruited a comprehensive set of paired primary tumor and Conclusions: The minimum difference between paired primary tumors and metastasis
distant metastatic clinical specimens of liver and colorectal cancer patients with the goal mutations beyond those needed for primary tumor formation.
of identifying metastasis-related genes. We performed gene expression profiling of laser
capture microdissected tumor and paired metastasis samples to ensure that the identified
genes are tumor-specific. In addition, we analyzed genome-wide somatic copy number
alteration (SCNA) profiling of paired primary tumors and distant metastasis of the same
patient. We also globally integrated gene expression and SCNA to identify key metastasis
genes.