Proteogenomic features define subtypes of mantle cell lymphoma

Area of Science:

• Oncology
• Proteomics
• Genomics

Background:

• Mantle cell lymphoma (MCL) is a heterogeneous B-cell malignancy with incompletely understood molecular underpinnings.
• Previous studies focused on genomics and transcriptomics, leaving the proteomic landscape of MCL largely unexplored.

Purpose of the Study:

• To conduct a comprehensive proteogenomic analysis of MCL.
• To investigate the translational and post-translational alterations in MCL.
• To identify novel molecular subtypes and prognostic markers for MCL.

Main Methods:

• Integrated analysis of genomics, transcriptomics, and proteomics on peripheral blood from MCL patients and healthy donors.
• Quantification of protein expression changes and correlation with genetic aberrations.
• Development of a multi-omics molecular stratification model for survival prediction.

Main Results:

• Identified 1,296 downregulated and 468 upregulated proteins in MCL cells.
• Observed significant upregulation of splicing pathways at both mRNA and protein levels.
• Found associations between IGHV mutational status, CCND1 mutation, and distinct molecular profiles with clinical outcomes.
• Demonstrated superior predictive power of a multi-omics model incorporating proteomics for patient survival (concordance index 0.83).

Conclusions:

• This study provides the first comprehensive proteogenomic profile of MCL.
• Aberrant RNA splicing plays a critical role in MCL pathogenesis.
• Proteomic signatures can refine molecular stratification and predict survival in MCL, supporting precision medicine approaches.