Proteogenomic Analysis of Human Colon Cancer Reveals New Therapeutic Opportunities


Suhas Vasaikar, Chen Huang, Xiaojing Wang, Vladislav A. Petyuk, Sara R. Savage, Bo Wen, et al., 2019 Cell 177(4) pages 1035-1049, DOI:https://doi.org/10.1016/j.cell.2019.03.030

We performed the first proteogenomic study on a prospectively collected colon cancer cohort. Comparative proteomic and phosphoproteomic analysis of paired tumor and normal adjacent tissues produced a catalog of colon cancer-associated proteins and phosphosites, including known and putative new biomarkers, drug targets, and cancer/testis antigens. Proteogenomic integration not only prioritized genomically inferred targets, such as copy-number drivers and mutation-derived neoantigens, but also yielded novel findings. Phosphoproteomics data associated Rb phosphorylation with increased proliferation and decreased apoptosis in colon cancer, which explains why this classical tumor suppressor is amplified in colon tumors and suggests a rationale for targeting Rb phosphorylation in colon cancer. Proteomics identified an association between decreased CD8 T cell infiltration and increased glycolysis in microsatellite instability-high (MSI-H) tumors, suggesting glycolysis as a potential target to overcome the resistance of MSI-H tumors to immune checkpoint blockade. Proteogenomics presents new avenues for biological discoveries and therapeutic development.

Proteomic data analyses detailed in this paper are available in the table below.
Raw mass spectrometry data for this study along with CPTAC Common Data Analysis Pipeline results may be obtained here.
Final data matrices are available at LinkedOmics (http://linkedomics.org/cptac-colon/), along with computational tools for further exploration of the CPTAC Colon Cancer Study (Vasaikar et al., 2018)
Genomic data from this study are available at the Sequence Read Archive (SRA), BioProject ID: PRJNA514017

Biospecimens


CPTAC Colon Cancer Prospective Collection Biospecimens
CPTAC Colon Cancer Prospective Collection Clinical Data
CPTAC Colon Cancer Prospective Collection 1 Year Follow-up Clinical Data

Data Types Available for Download


(ALL): Selection of this box downloads all data in the row
(raw): The original mass spectrometry(MS) instrument files
(mzML): HUPO-PSI standard raw data files generated from the original MS instrument files
(PSM): Peptide-Spectrum Match data
(prot): Protein assembly data and protein relative abundance
(meta): Clinical data files, mapping of biospecimens to iTRAQ labels or TMT10 labels (where applicable), folder and file naming conventions
Checksum files are included in all downloads for verification.

Data Sets


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BCM Baylor College of Medicine Bing Zhang, Ph.D.
PNNL Pacific Northwest National Laboratory Tao Liu, Ph.D.