TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma
<h4>Aims</h4> <p>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 upregulated transcript level has been reported in diffuse large B-cell lymphoma...
| Hoofdauteurs: | , , , , , , , |
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| Formaat: | Journal article |
| Gepubliceerd in: |
Wiley
2017
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| _version_ | 1826274906920189952 |
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| author | Loo, S Ch'ng, E Salleh, M Banham, A Pedersen, L Møller, M Green, T Wong, K |
| author_facet | Loo, S Ch'ng, E Salleh, M Banham, A Pedersen, L Møller, M Green, T Wong, K |
| author_sort | Loo, S |
| collection | OXFORD |
| description | <h4>Aims</h4> <p>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 upregulated transcript level has been reported in diffuse large B-cell lymphoma (DLBCL). We aim to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographical parameters and survival in DLBCL. </p> <h4>Methods and results</h4> <p>Analysis of publicly-available DLBCL microarray datasets showed that TRPM4 transcripts were upregulated in DLBCL compared to normal germinal centre B (GCB) cells, were more highly expressed in the activated B-cell-like DLBCL (ABC-DLBCL) subtype, and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP-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=49/189) of our cohort of R-CHOP-treated DLBCL cases and this was significantly associated with more aggressive clinical parameters including higher LDH, ECOG scores or stage (P<0.01 for each of the parameter) and the ABC-DLBCL subtype (P=0.016). TRPM4 positivity conferred significantly worse OS (P=0.004) and PFS (P=0.005). Worse OS remained significantly associated with TRPM4 positivity in multivariate analysis including higher international prognostic index (IPI) or the non-GCB DLBCL phenotype (P<0.05).</p> <h4>Conclusions</h4> <p>TRPM4 protein expression is upregulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patients’ outcomes.</p> |
| first_indexed | 2024-03-06T22:50:37Z |
| format | Journal article |
| id | oxford-uuid:5ea94e06-3bbd-4e08-b202-68e0757453f9 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:50:37Z |
| publishDate | 2017 |
| publisher | Wiley |
| record_format | dspace |
| spelling | oxford-uuid:5ea94e06-3bbd-4e08-b202-68e0757453f92022-03-26T17:42:00ZTRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphomaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5ea94e06-3bbd-4e08-b202-68e0757453f9Symplectic Elements at OxfordWiley2017Loo, SCh'ng, ESalleh, MBanham, APedersen, LMøller, MGreen, TWong, K <h4>Aims</h4> <p>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 upregulated transcript level has been reported in diffuse large B-cell lymphoma (DLBCL). We aim to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographical parameters and survival in DLBCL. </p> <h4>Methods and results</h4> <p>Analysis of publicly-available DLBCL microarray datasets showed that TRPM4 transcripts were upregulated in DLBCL compared to normal germinal centre B (GCB) cells, were more highly expressed in the activated B-cell-like DLBCL (ABC-DLBCL) subtype, and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP-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=49/189) of our cohort of R-CHOP-treated DLBCL cases and this was significantly associated with more aggressive clinical parameters including higher LDH, ECOG scores or stage (P<0.01 for each of the parameter) and the ABC-DLBCL subtype (P=0.016). TRPM4 positivity conferred significantly worse OS (P=0.004) and PFS (P=0.005). Worse OS remained significantly associated with TRPM4 positivity in multivariate analysis including higher international prognostic index (IPI) or the non-GCB DLBCL phenotype (P<0.05).</p> <h4>Conclusions</h4> <p>TRPM4 protein expression is upregulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patients’ outcomes.</p> |
| spellingShingle | Loo, S Ch'ng, E Salleh, M Banham, A Pedersen, L Møller, M Green, T Wong, K TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma |
| title | TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma |
| title_full | TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma |
| title_fullStr | TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma |
| title_full_unstemmed | TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma |
| title_short | TRPM4 expression is associated with activated B-cell subtype and poor survival in diffuse large B-cell lymphoma |
| title_sort | trpm4 expression is associated with activated b cell subtype and poor survival in diffuse large b cell lymphoma |
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