Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers.

TitleMass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers.
Publication TypeJournal Article
Year of Publication2021
AuthorsMonsivais, D, Vasquez, YM, Chen, F, Zhang, Y, Chandrashekar, DS, Faver, JC, Masand, RP, Scheurer, ME, Varambally, S, Matzuk, MM, Creighton, CJ
JournalOncogene
Volume40
Issue11
Pagination2081-2095
Date Published2021 Mar
ISSN1476-5594
Abstract

Proteomic signatures associated with clinical measures of more aggressive cancers could yield molecular clues as to disease drivers. Here, utilizing the Clinical Proteomic Tumor Analysis Consortium (CPTAC) mass-spectrometry-based proteomics datasets, we defined differentially expressed proteins and mRNAs associated with higher grade or higher stage, for each of seven cancer types (breast, colon, lung adenocarcinoma, clear cell renal, ovarian, uterine, and pediatric glioma), representing 794 patients. Widespread differential patterns of total proteins and phosphoproteins involved some common patterns shared between different cancer types. More proteins were associated with higher grade than higher stage. Most proteomic signatures predicted patient survival in independent transcriptomic datasets. The proteomic grade signatures, in particular, involved DNA copy number alterations. Pathways of interest were enriched within the grade-associated proteins across multiple cancer types, including pathways of altered metabolism, Warburg-like effects, and translation factors. Proteomic grade correlations identified protein kinases having functional impact in vitro in uterine endometrial cancer cells, including MAP3K2, MASTL, and TTK. The protein-level grade and stage associations for all proteins profiled-along with corresponding information on phosphorylation, pathways, mRNA expression, and copy alterations-represent a resource for identifying new potential targets. Proteomic analyses are often concordant with corresponding transcriptomic analyses, but with notable exceptions.

DOI10.1038/s41388-021-01681-0
Alternate JournalOncogene
PubMed ID33627787
PubMed Central IDPMC7981264
Grant ListCA125123 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
P20CA221729 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
P30 CA125123 / CA / NCI NIH HHS / United States
R00HD096057 / / Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) /
P20 CA221729 / CA / NCI NIH HHS / United States
RP160805 / / Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) /
R00 HD096057 / HD / NICHD NIH HHS / United States