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

Suet K. Loo, Ewe S. Ch'ng, Md Salzihan Md Salleh, Alison H Banham, Lars M. Pedersen, Michael B. Møller, Tina M. Green, Kah Keng Wong

Research output: Contribution to journalJournal articleResearchpeer-review


Aims: Transient receptor potential channel melastatin 4 (TRPM4) is an ion channel that regulates influx of calcium cations (Ca2+). Recent studies suggest that TRPM4 is an oncoprotein, and its up-regulated transcript level has been reported in diffuse large B cell lymphoma (DLBCL). We aimed to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL. Methods and results: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05). Conclusions: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.

Original languageEnglish
Issue number1
Pages (from-to)98–111
Publication statusPublished - Jul 2017


  • Diffuse large B cell lymphoma
  • Immunohistochemistry
  • Prognosis
  • TRPM4
  • TRPM Cation Channels/analysis
  • Up-Regulation
  • Humans
  • Middle Aged
  • Kaplan-Meier Estimate
  • Male
  • Disease-Free Survival
  • B-Lymphocytes/immunology
  • Biomarkers, Tumor/analysis
  • Lymphocyte Activation/immunology
  • Lymphoma, Large B-Cell, Diffuse/mortality
  • Adult
  • Female
  • Aged


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