Specifically, protein groups in cluster 1 were relevant to cell development, such as regulation of cytoskeleton organization, regulation of protein-containing complex assembly, and supramolecular fiber organization. Cluster 2 was characterized by ribosome biogenesis for cell proliferation and immune response to the microenvironment. Ribosomal proteins (RPs) of the 60S (e.g., RPL3, RPL5, and RPL14) and 40S (e.g., RPS6, RPS8, and RPS16) were enriched in clusters 2 and 3 (Figure 3C and D). Cell proliferation-related proteins for pre-mRNA processing (e.g., HNRNPA1, HNRNPK, and HNRNPL), core spliceosome (e.g., SRSF1, SF3B3, and SFPQ), and proteasome complex (e.g., PSMC3, PSMA4, and PSMB1) were present in cluster 2. Moreover, a unit of proteins (ILF2, ILF3, ISG15, and XRCC6) involved in the modulation of the tumor microenvironment by the inflammatory was identified. Further, cluster 3 encompassed energy metabolism and RNA translation for tumorigenesis.
FIGURE 3 Distinct features of BrM proteome profile. A Unsupervised clustering of the top 1000 protein features out of 3843 label free quantification (LFQ) proteins based on their interquartile range (IQR) in 14 samples of BrMs. Pearson correlation was used for distance measurement. BGene set enrichment analysis (GSEA) of proteins in the three clusters. The top 20 annotations of GO-BP, Reactome, WikiPathways, and KEGG pathways are shown (Benjamini−Hochberg FDR method, adjusted P < 0.01).C Protein enrichment networks in cluster 2 based on the top three functional enriched terms (R-HSA-8953854, R-HSA-2262752, and R-HSA-8953897) (Benjamini−Hochberg FDR method, adjusted P < 0.01). D Protein enrichment networks in cluster 3 based on the top three functional enriched terms (R-HSA-72766, GO:0006412, and GO:0043043) (Benjamini−Hochberg FDR method, adjusted P < 0.01).