3.4 Comparative proteomics for primary and secondary brain
tumors
Gliomas
and BrMs are the most predominant primary and secondary brain tumors in
the human brain with a common trait of various malignancies. We next
investigated the proteomic heterogeneity of these two types of brain
tumors. These two typical brain tumors are composed of unique cell
types, anatomical structures, metabolic constraints, and immune
environment [17] , which may explain the tendency of some
extracranial cancers to migrate toward the brain and provide new
insights into the blood-brain
barrier (BBB) changes during tumor metastasis. For comparative proteomic
analysis, malignant brain tumors from primary (gliomas, n = 13)
and secondary (BrMs, n = 14) brain tumors were utilized.
In total, 352 proteins were
statistically different between the cohorts (P < 0.01),
of which 93 proteins were upregulated and 259 proteins were
downregulated in BrMs versus gliomas (Figure 5A, Figure S4A and Table
S3). The 352 DEPs effectively
distinguished two types of tumors in unsupervised clustering and PCA
based on component 1 (96.1%) and component 2 (1.8%) (Figure 5B and
Figure S4B).
We next performed functional enrichment analysis for the upregulated and
downregulated proteins, respectively (Figure 5C, Figure S4C and D). To
some extent, the general cellular and molecular pathways were similar in
both types of malignant brain tumors. However, proteins in some distinct
pathways were upregulated in BrMs, such as Golgi vesicle transport,
formation of the cornified envelope, and secretion (Figure 5C and Figure
S4C). Specific processes involved in gliomas were correlated with cell
migration, including regulation of actin cytoskeleton, modulation of
chemical synaptic transmission, neuron projection development and so on.
Taken together, the proteome-based results clearly illustrated that BrM
colonization in the brain depends on tumorigenesis and multiple
interactions of metastatic cancer cells with the brain microenvironment,
whereas gliomas, as one of the representative primary tumors in the
brain, maintain a high tendency to invade. These findings prompted
further exploration of candidate biomarkers for distinguishing primary
and secondary brain tumors.