Introduction
Human tumor-derived cell lines are widely used to study cancer biology and therapy, but controversy remains whether cell lines provide appropriate representation of primary tumors. Here, we report an integrative proteogenomic analysis of human colorectal cancer (CRC) cell lines, primary tumors and corresponding normal tissues.
We found a significant, systematic difference between cell line and tumor proteomes, with major differences arising from tumor stroma. Nevertheless, cell lines mirrored the proteomic differences between tumors and normal tissues, in particular for intrinsic molecular programs, indicating that cell lines provide informative models for cancer cells in vivo. The intersection of cell line and tumor data identified tumor cell-specific proteome alterations driven by genomic aberrations. Our integration of cell line proteogenomic data with drug sensitivity measurements highlights the potential of proteomic data for predicting therapeutic responses. We identified representative cell lines for all proteomic subtypes of primary tumors with evidence for subtype-specific drug responses.
(Note: Manuscript is under review. For more information mail to Dr. Bing Zhang (bing.zhang@bcm.edu) or Oliver M. Sieber (sieber.o@wehi.edu.au))
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