Platform independent protein-based cell-of-origin subtyping of diffuse large B-cell lymphoma in formalin-fixed paraffin-embedded tissue

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Scientific reports - 10(2020), 1 vom: 12. Mai, Seite 7876

Sprache:

Englisch

Beteiligte Personen:

Reinders, Jörg [VerfasserIn]
Altenbuchinger, Michael [VerfasserIn]
Limm, Katharina [VerfasserIn]
Schwarzfischer, Philipp [VerfasserIn]
Scheidt, Tamara [VerfasserIn]
Strasser, Lisa [VerfasserIn]
Richter, Julia [VerfasserIn]
Szczepanowski, Monika [VerfasserIn]
Huber, Christian G [VerfasserIn]
Klapper, Wolfram [VerfasserIn]
Spang, Rainer [VerfasserIn]
Oefner, Peter J [VerfasserIn]

Links:

Volltext

Themen:

1HG84L3525
Formaldehyde
Journal Article
Proteins
Proteome
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 30.11.2020

Date Revised 12.05.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-020-64212-z

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM309818176