TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

Area of Science:

• Ion channel function in oncology
• Molecular mechanisms of B-cell lymphomas

Background:

• Transient receptor potential channel melastatin 4 (TRPM4) regulates calcium influx and is implicated as an oncoprotein.
• TRPM4 transcript levels are elevated in diffuse large B cell lymphoma (DLBCL).

Purpose of the Study:

• To investigate TRPM4 protein expression in DLBCL and non-malignant tissues.
• To assess the association of TRPM4 expression with DLBCL subtypes, clinical parameters, and patient survival.

Main Methods:

• Analysis of publicly available DLBCL microarray data.
• Immunohistochemical analysis of TRPM4 protein expression in DLBCL patient cohorts.
• Correlation analysis with clinical and demographic parameters and survival data.

Main Results:

• TRPM4 transcripts were upregulated in DLBCL, especially in the activated B cell-like (ABC-DLBCL) subtype, and associated with worse overall survival (OS).
• TRPM4 protein was expressed in 26% of DLBCL cases, correlating with aggressive clinical parameters (higher LDH, ECOG, stage) and ABC-DLBCL subtype.
• TRPM4 positivity significantly predicted worse OS and progression-free survival (PFS), remaining significant in multivariate analysis.

Conclusions:

• TRPM4 protein is upregulated in DLBCL compared to non-malignant B cells.
• Preferential expression in ABC-DLBCL cases suggests a role in disease aggressiveness.
• TRPM4 expression is a significant negative prognostic marker for DLBCL patient outcomes.