Colorectal cancer cell lines lack the molecular heterogeneity of clinical colorectal tumors

Abstract

Background: Histologically similar colorectal cancers (CRCs) exhibit a wide range of outcomes, suggesting that knowledge of the molecular differences might provide insight into this heterogeneity. Cancer cell lines have been used in preclinical studies to identify gene expression alterations that influence response to chemotherapeutic agents. However, it is not clear to what extent available CRC cell lines reflect the molecular heterogeneity observed in clinical colorectal tumors.

Materials and methods: We compared genome-wide gene expression data from 22 CRC cell lines and 276 clinical colorectal tumors to determine whether the cell lines were able to represent the variability in expression profiles seen in the clinical tissues. Following mean centered data normalization, hierarchical clustering was performed on the samples using literature-derived biologic and pharmacogenomic gene sets.

Results: In general, the majority of cell lines tended to cluster together in a single group, as a subcluster within the clinical tissues, although a few cell lines showed distinct expression profiles from the majority of cell lines.

Conclusion: The gene expression data comparison suggests that CRC cell lines do not adequately reflect the molecular heterogeneity of clinical colorectal tumors.