This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Varghese, S. Articles by Alexander, H. R. Search for Related Content PubMed Articles by Varghese, S. Articles by Alexander, H. R.

Site-Specific Gene Expression Profiles and Novel Molecular Prognostic Factors in Patients with Lower Gastrointestinal Adenocarcinoma Diffusely Metastatic to Liver or Peritoneum

¹ Division of Surgical Oncology, Department of Surgery, University of Maryland School of Medicine and the Marlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, 21201, USA
² Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA

Correspondence: Address correspondence and reprint requests to: H. Richard Alexander; E-mail: HRAlexander{at}smail.umaryland.edu

Background: Generally, colorectal and high-grade appendiceal cancers are treated similarly; treatment approach is primarily based on tumor histology and stage of disease. Patients with adenocarcinoma of the lower gastrointestinal tract frequently experience diffuse metastases isolated to liver or peritoneum and have a poor survival. Identification of novel molecular pathways in metastases from these patients may identify novel targets and prognostic factors.

Methods: Microarray analyses of 20 metastatic tumors from patients with colorectal adenocarcinoma isolated to liver or peritoneum and eight high-grade appendiceal adenocarcinoma metastatic to peritoneum were performed using oligonucleotide microarray.

Results: In an unsupervised hierarchical cluster analysis of 2-fold upregulated or down-regulated genes, there was a clear site-specific segregation of liver versus peritoneal metastases. Genes primarily involved in metastasis, angiogenesis, cell cycle regulation, cell proliferation, and cell adhesion were distinctly altered between these two metastatic sites. Among the metastasis genes, the average expression levels of LI-cadherin, ALCAM, CD2, and CD14 were significantly higher in both metastatic sites. TIMP1 was overexpressed in both sites where as TIMP-2, IGF-1, and HIF-1 were upregulated only in peritoneal metastases demonstrating the potential benefit of metastasis site-specific treatments. Subsets of genes significantly associated with poor survival were defined, a RET proto-oncogene interacting gene, GOL-GA5, was highly predictive for survival in patients with colorectal adenocarcinoma.

Conclusions: These results demonstrate that liver and peritoneal metastases of lower GI adenocarcinoma have distinct gene expression patterns; these distinctions may help in the development of therapies based on site of metastases.

Key Words: Colorectal cancer • GI adenocarcinoma • Metastases • Microarray