Investigators from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) who comprehensively analyzed 95 human colorectal tumor samples, have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, provides a more comprehensive view of the biological features that drive cancer than genomic analysis alone and may help identify the most important targets for cancer detection and intervention. The results of this study appeared online July 20, 2014, in Nature.
The colorectal study produced several key findings:
- Measurements of messenger RNA abundance did not reliably predict protein abundance. The investigators were not surprised by this discordance, because many regulatory controls lie between RNA and protein expression. However, it did demonstrate that RNA analyses do not necessarily give a correct indication of protein levels.
- Most of the focal amplifications (increased amounts of certain chromosome segments) observed in the earlier genomic analyses of the same tumors did not result in corresponding elevations in protein level. Proteomic analyses identified a few amplifications that had dramatic effects on protein levels and may represent potentially important targets for diagnosis or therapeutic intervention.
- Proteomics identified five colon cancer subtypes, including classifications that could not be derived from genomic data. Protein expression signatures for one of the subtypes indicated molecular characteristics associated with highly aggressive tumors with poor clinical outcome.
“This study provides the first clear demonstration that proteomics can help explain how genomic abnormalities drive cancer,” said senior author of the study, Daniel C. Liebler, Ph.D, Director, Jim Ayers Institute for Precancer Detection and Diagnosis, Vanderbilt University School of Medicine.
This study, by CPTAC investigators, was made possible because it utilized the same set of tumors that were genomically analyzed in 2012 by The Cancer Genome Atlas (TCGA).
“These findings show that by combining proteomic and genomic analyses, one is able to gain additional biological information for a disease,” said Henry Rodriguez, Ph.D., M.B.A., Director of the Office of Cancer Clinical Proteomics Research, National Cancer Institute.