Reproducibility of Gene Expression Signatures in Diffuse Large B-Cell Lymphoma.
Simple Summary: Multiple gene expression signatures with biological or prognostic subgroups have been published in diffuse large B-cell lymphoma (DLBCL). With exception of the cell of origin (COO) classifier, these were not validated in independent cohorts. The aim of the study was to reproduce four...
| Publicado en: | Cancers Vol. 14; no. 5; pp. 1346 - 1347 |
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| Autores principales: | , , , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
MDPI
Mar2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=155707544&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 155707544 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Mar2022 vid: 14 iid: 5 pid: 97109 pub: MDPI artinfo: ui: 155707544 155707544 155707544 10.3390/cancers14051346 155707544 ppf: 1346 ppct: 1 formats: tig: atl: Reproducibility of Gene Expression Signatures in Diffuse Large B-Cell Lymphoma. aug: au: Plaça, Jessica Rodrigues Diepstra, Arjan Los, Tjitske Mendeville, Matías Seitz, Annika Lugtenburg, Pieternella J. Zijlstra, Josée Lam, King da Silva Jr., Wilson Araújo Ylstra, Bauke de Jong, Daphne van den Berg, Anke Nijland, Marcel affil: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9712 Groningen, The Netherlands sug: subj: Gene Expression Profiling Lymphoma, B-Cell Familial and Genetic Lymphoma, B-Cell Molecular Biology Human Prospective Studies Cancer Patients Comparative Studies Descriptive Statistics Algorithms Phosphorylation Lymphoid Tissue Signal Transduction ab: Simple Summary: Multiple gene expression signatures with biological or prognostic subgroups have been published in diffuse large B-cell lymphoma (DLBCL). With exception of the cell of origin (COO) classifier, these were not validated in independent cohorts. The aim of the study was to reproduce four gene expression signatures capturing multiple biological subgroups using the NanoString platform. In addition, we aimed to identify potential associations between the signatures and portray the heterogeneity of DLBCL. We show that, in an independent cohort of clinically well-defined patients, these signatures can co-occur in the same patient and that each classifier captures a different aspect of the biological heterogenous panorama of DLBCL. Beside COO, there is clear evidence of different immune and MYC signatures. A direct comparison in our cohort showed that these signatures reflect independent biological features. More comparative studies with gene expression profiles need to be conducted to enable a further integration and to help develop new taxonomy systems for clinical utility. Multiple gene expression profiles have been identified in diffuse large B-cell lymphoma (DLBCL). Besides the cell of origin (COO) classifier, no signatures have been reproduced in independent studies or evaluated for capturing distinct aspects of DLBCL biology. We reproduced 4 signatures in 175 samples of the HOVON-84 trial on a panel of 117 genes using the NanoString platform. The four gene signatures capture the COO, MYC activity, B-cell receptor signaling, oxidative phosphorylation, and immune response. Performance of our classification algorithms were confirmed in the original datasets. We were able to validate three of the four GEP signatures. The COO algorithm resulted in 94 (54%) germinal center B-cell (GCB) type, 58 (33%) activated B-cell (ABC) type, and 23 (13%) unclassified cases. The MYC-classifier revealed 77 cases with a high MYC-activity score (44%) and this MYC-high signature was observed more frequently in ABC as compared to GCB DLBCL (68% vs. 32%, p < 0.00001). The host response (HR) signature of the consensus clustering was present in 55 (31%) patients, while the B-cell receptor signaling, and oxidative phosphorylation clusters could not be reproduced. The overlap of COO, consensus cluster and MYC activity score differentiated six gene expression clusters: GCB/MYC-high (12%), GCB/HR (16%), GCB/non-HR (27%), COO-Unclassified (13%), ABC/MYC-high (25%), and ABC/MYC-low (7%). In conclusion, the three validated signatures identify distinct subgroups based on different aspects of DLBCL biology, emphasizing that each classifier captures distinct molecular profiles. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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