Reinders, Joerg and Altenbuchinger, Michael and Limm, Katharina and Schwarzfischer, Philipp and Scheidt, Tamara and Strasser, Lisa and Richter, Julia and Szczepanowski, Monika and Huber, Christian G. and Klapper, Wolfram and Spang, Rainer and Oefner, Peter J. (2020) Platform independent protein-based cell-of-origin subtyping of diffuse large B-cell lymphoma in formalin-fixed paraffin-embedded tissue. SCIENTIFIC REPORTS, 10 (1): 7876. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Diffuse large B-cell lymphoma (DLBCL) is commonly classified by gene expression profiling according to its cell of origin (COO) into activated B-cell (ABC)-like and germinal center B-cell (GCB)-like subgroups. Here we report the application of label-free nano-liquid chromatography - Sequential Window Acquisition of all THeoretical fragment-ion spectra - mass spectrometry (nanoLC-SWATH-MS) to the COO classification of DLBCL in formalin-fixed paraffin-embedded (FFPE) tissue. To generate a protein signature capable of predicting Affymetrix-based GCB scores, the summed log(2)-transformed fragment ion intensities of 780 proteins quantified in a training set of 42 DLBCL cases were used as independent variables in a penalized zero-sum elastic net regression model with variable selection. The eight-protein signature obtained showed an excellent correlation (r=0.873) between predicted and true GCB scores and yielded only 9 (21.4%) minor discrepancies between the three classifications: ABC, GCB, and unclassified. The robustness of the model was validated successfully in two independent cohorts of 42 and 31 DLBCL cases, the latter cohort comprising only patients aged >75 years, with Pearson correlation coefficients of 0.846 and 0.815, respectively, between predicted and NanoString nCounter based GCB scores. We further show that the 8-protein signature is directly transferable to both a triple quadrupole and a Q Exactive quadrupole-Orbitrap mass spectrometer, thus obviating the need for proprietary instrumentation and reagents. This method may therefore be used for robust and competitive classification of DLBCLs on the protein level.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE; MOLECULAR CLASSIFICATION; KAPPA-B; SIGNATURES; SURVIVAL; MYC; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2021 08:38 |
| Last Modified: | 24 Mar 2021 08:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44576 |
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