{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:27:35Z","timestamp":1790270855911,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,4,27]],"date-time":"2017-04-27T00:00:00Z","timestamp":1493251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004595","name":"Universiti Sains Malaysia","doi-asserted-by":"publisher","award":["1001\/PPSP\/813054"],"award-info":[{"award-number":["1001\/PPSP\/813054"]}],"id":[{"id":"10.13039\/501100004595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004196","name":"Odense Universitetshospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2017,7]]},"abstract":"\n Aims<\/jats:title>\n \n Transient receptor potential channel melastatin 4 (\n TRPM<\/jats:styled-content>\n 4) is an ion channel that regulates influx of calcium cations (Ca\n 2+<\/jats:sup>\n ). Recent studies suggest that\n TRPM<\/jats:styled-content>\n 4 is an oncoprotein, and its up\u2010regulated transcript level has been reported in diffuse large B cell lymphoma (\n DLBCL<\/jats:styled-content>\n ). We aimed to investigate\n TRPM<\/jats:styled-content>\n 4 protein expression pattern in non\u2010malignant tissues and\n DLBCL<\/jats:styled-content>\n cases, and its association with clinico\u2010demographic parameters and survival in\n DLBCL<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and results<\/jats:title>\n \n Analysis of publicly available\n DLBCL<\/jats:styled-content>\n microarray data sets showed that\n TRPM4<\/jats:italic>\n transcripts were up\u2010regulated in\n DLBCL<\/jats:styled-content>\n compared to normal germinal centre B (\n GCB<\/jats:styled-content>\n ) cells, were expressed more highly in the activated B cell\u2010like\n DLBCL<\/jats:styled-content>\n (\n ABC<\/jats:styled-content>\n \u2010\n DLBCL<\/jats:styled-content>\n ) subtype and higher\n TRPM4<\/jats:italic>\n transcripts conferred worse overall survival (\n OS<\/jats:styled-content>\n ) in R\u2010\n CHOP<\/jats:styled-content>\n (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)\u2010treated\n DLBCL<\/jats:styled-content>\n cases (\n P<\/jats:italic>\n < 0.05). Our immunohistochemical analysis showed that\n TRPM<\/jats:styled-content>\n 4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix).\n TRPM<\/jats:styled-content>\n 4 protein was present in 26% (\n n<\/jats:italic>\n = 49 of 189) of our cohort of R\u2010\n CHOP<\/jats:styled-content>\n \u2010treated\n DLBCL<\/jats:styled-content>\n cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (\n LDH<\/jats:styled-content>\n ), Eastern Cooperative Oncology Group (\n ECOG<\/jats:styled-content>\n ) scores or stage (\n P<\/jats:italic>\n < 0.01 for each of the parameters) and the\n ABC<\/jats:styled-content>\n \u2010\n DLBCL<\/jats:styled-content>\n subtype (\n P<\/jats:italic>\n = 0.016).\n TRPM<\/jats:styled-content>\n 4 positivity conferred significantly worse\n OS<\/jats:styled-content>\n (\n P<\/jats:italic>\n = 0.004) and progression\u2010free survival (\n PFS<\/jats:styled-content>\n ) (\n P<\/jats:italic>\n = 0.005). Worse\n OS<\/jats:styled-content>\n remained associated significantly with\n TRPM<\/jats:styled-content>\n 4 positivity in multivariate analysis, including higher International Prognostic Index (\n IPI<\/jats:styled-content>\n ) or the non\u2010\n GCB DLBCL<\/jats:styled-content>\n phenotype (\n P<\/jats:italic>\n < 0.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n TRPM<\/jats:styled-content>\n 4 protein expression is up\u2010regulated in\n DLBCL<\/jats:styled-content>\n cases compared to non\u2010malignant B cells with preferential expression in\n ABC<\/jats:styled-content>\n \u2010\n DLBCL<\/jats:styled-content>\n cases, and it confers significantly poorer\n DLBCL<\/jats:styled-content>\n patient outcomes.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.13204","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T09:22:51Z","timestamp":1488360171000},"page":"98-111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma"],"prefix":"10.1111","volume":"71","author":[{"given":"Suet K","family":"Loo","sequence":"first","affiliation":[{"name":"Department of Immunology School of Medical Sciences Universiti Sains Malaysia Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewe S","family":"Ch'ng","sequence":"additional","affiliation":[{"name":"Advanced Medical and Dental Institute Universiti Sains Malaysia Bertam Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Salzihan","family":"Md Salleh","sequence":"additional","affiliation":[{"name":"Department of Pathology School of Medical Sciences Universiti Sains Malaysia Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison H","family":"Banham","sequence":"additional","affiliation":[{"name":"Nuffield Division of Clinical Laboratory Sciences Radcliffe Department of Medicine University of Oxford John Radcliffe Hospital Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars M","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Haematology Herlev University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Pathology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina M","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pathology Odense University Hospital Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-6202","authenticated-orcid":false,"given":"Kah K","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Immunology School of Medical Sciences Universiti Sains Malaysia Kelantan Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2015.06.002"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-016-9634-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.11.032"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308802200"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708459200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2010.01.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.5582\/bst.8.1"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00719-5"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098845"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2014.02.001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0130540"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1648"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2008.10.005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20418"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0020"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-015-1880-y"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6157"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/35000501"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-12-322362"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2006.00267.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-02-0542"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08638"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055895"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.11.023"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19352"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.38"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080809"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07968"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0802885"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2012.83"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055759"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa055351"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-01-330795"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-12-0095"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.57.7080"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexmp.2015.08.019"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.4342"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.224"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.299"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9507"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27674"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-016-1988-8"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305127200"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1545"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvr135"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-013-1347-4"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0501-x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv213"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2016.01.052"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0432-3"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1441"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207174200"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.39"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.14.146"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-237537"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02720.x"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07193.x"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2011.12.018"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000880"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12381"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102969"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062041"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10351"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09671"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.006"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0599-2"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1245"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109980"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3304"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.13204","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.13204","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T22:22:13Z","timestamp":1696285333000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.13204"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,27]]},"references-count":70,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,7]]}},"alternative-id":["10.1111\/his.13204"],"URL":"https:\/\/doi.org\/10.1111\/his.13204","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,4,27]]},"assertion":[{"value":"2016-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-02-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}