Proteogenomic analysis of human colon cancer reveals new therapeutic opportunities
By S. Vasaikar, Chen Huang, Xiaojing Wang, V. Petyuk, Sara R. Savage, Bo Wen, Yongchao Dou, Yun Zhang, Zhiao Shi, O. A. Arshad and 22 more. Cell, 2019
663 citations recorded by the source corpus.
Summary 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 catalogue 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.
Subfields: Biotechnology, Cancer Research, Oncology
View Paper: https://www.semanticscholar.org/paper/3ce770e03f974f2f21daa1bd77ab0f7394396652
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Oncology
Citations in the corpus
- Quantitative Proteomics of the Cancer Cell Line Encyclopedia (2020, positive): “Recently, proteomic studies of several cancers have rediscovered many of the same subtypes found by gene expression, as well as new disease categorizations, highlighting the gains from studying the proteome (Mertins et al., 2016; Pozniak et al., 2016; Zhang et al., 2014, 2016; Vasaikar et al., 2019)”