Platform independent protein-based cell-of-origin subtyping of diffuse large B-cell lymphoma in formalin-fixed paraffin-embedded tissue
2020 | journal article; research paper
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Reinders, Jörg, Michael Altenbuchinger, Katharina Limm, Philipp Schwarzfischer, Tamara Scheidt, Lisa Strasser, Julia Richter et al. "Platform independent protein-based cell-of-origin subtyping of diffuse large B-cell lymphoma in formalin-fixed paraffin-embedded tissue." Scientific Reports 10, no. 1 (2020): 7876. https://doi.org/10.1038/s41598-020-64212-z.
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Details
- Authors
- Reinders, Jörg; Altenbuchinger, Michael ; Limm, Katharina; Schwarzfischer, Philipp; Scheidt, Tamara; Strasser, Lisa; Richter, Julia; Szczepanowski, Monika; Huber, Christian G.; Klapper, Wolfram; Spang, Rainer; Oefner, Peter J.
- 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 log2-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.
- Issue Date
- 2020
- Journal
- Scientific Reports
- ISSN
- 2045-2322
- Language
- English