Abstract 5243: Gene expression analysis of CRC liver metastases with different growth patterns

Abstract

Abstract Introduction: Liver metastases of colorectal cancer (CRC) grow according to different growth patterns (GPs) with different angiogenic properties. The aim of this study was to characterize these GPs on a molecular level using genome-wide gene expression analysis. Materials and Methods: On 18 CRC liver metastases of which genome-wide gene expression data were available from a previous study (publicly available at GSE 10961), we assessed the GP using a haematoxylin-eosin and Gordon Sweet's reticulin stain. 7 metastases had a desmoplastic GP, 6 had a pushing GP and 3 had a replacement GP. Of 2 metastases the GP could not be assessed due to lack of sufficient material and these were excluded for further analysis. We used (hierarchical) cluster analysis, principal component analysis, significance/prediction analysis of microarrays and gene set enrichment analysis to study differences in gene expression between the different GPs. Results: Principal component analysis and hierarchical cluster analysis showed significant gene expression differences between metastases with a desmoplastic and pushing GP (p=2.2e−16) and between metastases with a desmoplastic and replacement GP (p=2.2e−16). Gene set enrichment analysis demonstrated increased expression of biological processes, molecular functions, cellular components and KEGG pathways related to immune response, antigen processing, leucocyte activation and cell adhesion molecules in the metastases with a desmoplastic GP. Similar differences were found when metastases with a pushing GP were compared to metastases with a replacement GP and when the 3 groups were compared. Conclusion: These results confirm on a molecular level that liver metastases of patients with CRC have a heterogeneous biology. Metastases with a desmoplastic GP appear to have upregulation of immunological processes, compared to metastases with a pushing or replacement GP. Further elucidation of these differences might lead to better understanding of host-tumour interactions in metastatic biology and new therapeutic strategies for patients with metastatic CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5243. doi:10.1158/1538-7445.AM2011-5243