Mass-spectrometry-based proteomic correlates of grade and stage reveal pathways and kinases associated with aggressive human cancers
| Autor: | Michael E. Scheurer, Sooryanarayana Varambally, Martin M. Matzuk, Fengju Chen, Yasmin M. Vasquez, Yiqun Zhang, Chad J. Creighton, Ramya P. Masand, Diana Monsivais, John C. Faver, Darshan S. Chandrashekar |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Proteomics 0301 basic medicine Cancer Research Cell Cycle Proteins Disease MAP Kinase Kinase Kinase 2 Protein Serine-Threonine Kinases MAP3K2 Biology Article Transcriptome 03 medical and health sciences 0302 clinical medicine Neoplasms Genetics medicine Humans Molecular Biology Neoplasm Staging Kinase Phosphotransferases Cancer Protein-Tyrosine Kinases Phosphoproteins medicine.disease Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis Cancer research Adenocarcinoma Female Neoplasm Grading Microtubule-Associated Proteins Clear cell |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-021-01681-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink