Proteomes
Proteomic Profiling of Immune Cell Infiltration Reveals Prognostic Immune Subtypes in Lung Adenocarcinoma
By Ruoxian Zhang, Haipeng Guo, Xianju Li and 2 others.
Abstract
Background
Lung adenocarcinoma (LUAD) shows marked heterogeneity in its immune microenvironment, which may contribute to differences in disease-free survival (DFS) and clinical outcome. Although current LUAD classifications are largely based on genomic or transcriptomic features, immune subtypes defined directly from bulk proteomic data remain poorly characterized. Here, we used an immune-cell proteomic reference matrix to investigate proteome-defined immune states in LUAD and to identify prognostically relevant immune subtypes.
Methods
A quantitative human immune-cell proteomic reference matrix was integrated with LUAD tumor proteomic profiles. The reference matrix covered seven major immune lineages and 26 immune-cell states. The discovery cohort included 101 LUAD tumor proteomes with matched clinical information. After gene symbol matching and normalization, proteome-defined immune-cell state signals were estimated for each sample using non-negative constrained regression. These signals were then used for unsupervised subtype identification and DFS analysis. An independent Clinical Proteomic Tumor Analysis Consortium (CPTAC)-LUAD cohort was used for validation, with subtype analysis performed at the immune-cell marker protein module level.