High resolution proteome profiling of multiple neighboring regions with each tumor tissue of patients with melanoma brain metastasis using bulk tumor sequencing.

ABSTRACT: Our study provides a comprehensive multiomics overview of each patient’s tumor, revealing tumor cell types, proteomics, and transcriptomic changes related to melanoma brain metastasis (MBM). Here, we have applied the HiRIEF pre-fractionation and tandem mass tags (TMT)-16plex based peptide quantification to generate proteomes of multiple neighboring regions within each MBM tumor tissue. PCA and Hierarchical clustering analysis illustrated higher inter-tumoral heterogeneity than intra-tumoral heterogeneity of MBM at the protein levels, as lesions from the same patients are grouped into a single cluster. The treatment-naive patient (P3) exhibited high intra-tumoral heterogeneity (ITH) compared to treated ones, with ITH levels varying across neighboring regions in patient tumors. Differential expression analysis highlighted enriched protein and gene clusters for all patient comparisons, including innate immune proteins, macrophage activation, T- and B-cell signaling, and key cancer pathways (e.g., epithelial-mesenchymal transition, cell adhesion, notch signaling, oxidative phosphorylation and cell cycle checkpoints). Genes involved in functional processes characteristic of MBM cell types, tumor-immune interactions, and signaling mechanisms were more highly correlated with their protein levels. Overall, our results provide a comprehensive spatial and molecular view of intra-tumoral and inter-tumoral heterogeneity in MBM.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Nidhi Sharma  

LAB HEAD: Janne Lehtiö

PROVIDER: PXD055170 | Pride | 2025-07-21

REPOSITORIES: Pride