CCL18: a potential immunosuppressive biomarker for prognosis in ABC diffuse large B-cell lymphoma

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL) exhibits worse patient outcomes compared to the germinal center B-cell (GCB) subtype.
• The underlying molecular mechanisms contributing to the differential outcomes of ABC and GCB DLBCL remain incompletely understood.

Purpose of the Study:

• To elucidate the molecular differences between ABC and GCB DLBCL subtypes.
• To identify novel prognostic biomarkers and therapeutic targets for ABC DLBCL.

Main Methods:

• Transcriptomic analysis of DLBCL samples using the NanoString PanCancer Immune Profiling Panel.
• Tumor microenvironment characterization via CIBERSORTx and gene set enrichment analysis (GSEA).
• Analysis of MAPK10 promoter methylation, Cox regression, LASSO regularization, and connectivity mapping for biomarker and therapeutic candidate identification.

Main Results:

• ABC lymphomas displayed distinct gene expression profiles, including overexpression of VTCN1, CDK4, CXCR5 and downregulation of MMP9, MAPK10.
• MAPK10 downregulation in ABC tumors correlated with promoter hypermethylation and poorer overall survival.
• CCL18 was identified as an independent adverse prognostic factor, while high CD8+ T-cell abundance correlated with improved survival, especially in ABC patients.

Conclusions:

• MAPK10 promoter hypermethylation and CCL18 overexpression are validated prognostic biomarkers in ABC DLBCL.
• Integrative transcriptomic and immunogenomic profiling offers insights into DLBCL biology.
• Findings support biomarker-guided strategies for precision treatment in aggressive B-cell lymphomas.