Abstract
Purpose: Brain tumors, whether primary or secondary, have
limited information about proteomic
changes
despite advances in the understanding of the driver gene mutations and
heterogeneity
within tumor
cells.
The purpose of this study is to distinguish primary and secondary brain
tumors based on proteomics.
Experimental Design: We assembled the most common primary
tumors as follows: gliomas from WHO grade II to IV with or withoutIDH1 mutations; and BrMs with a wide range, including
lung cancer (L.C), breast cancer
(B.C), ovarian cancer (O.C), and colorectal cancer (C.C).
A total of 29 tissue samples were
analyzed by label free quantitative mass spectrometry-based proteomics.
Results: In total, 8,370 protein groups were identified, and
approximately 4,000 quantified protein groups were adopted for further
analysis.
Proteomic analysis of metastatic tumors reveals conserved features
across multiple cancers. While proteomic heterogeneities were found for
discriminating low- and high-grade of gliomas, as well as IDH1 mutant
and wild-type gliomas.
And
distinct pathway-level differences among these two types of brain
malignancies were
revealed.
The characteristic pathways of BrMs focused on proliferation and
immunomodulation
after colonizing the brain, whereas invasion processes were notably
activated in
gliomas.
Conclusions and Clinical Relevance:We
elucidated an extensive proteomic landscape of BrMs and gliomas,
providing information for the development of
potential therapeutic and
diagnostic
strategies for type-specific brain tumors.