TY - JOUR
T1 - The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients
T2 - a labelled and label-free proteomics approach
AU - van Leeuwen, S. J. M.
AU - Proctor, G. B.
AU - Staes, A.
AU - Laheij, A. M. G. A.
AU - Potting, C. M. J.
AU - Brennan, M. T.
AU - von Bültzingslöwen, I.
AU - Rozema, F. R.
AU - Hazenberg, M. D.
AU - Blijlevens, N. M. A.
AU - Raber-Durlacher, J. E.
AU - Huysmans, M. C. D. N. J. M.
N1 - Funding Information: This research was funded by the Dutch Cancer Society (KWF Kankerbestrijding (NL); ACTA 2014–7468). The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. Funding Information: For the execution of the TMT-labelled experiment we want to thank S. Lynham from the proteomics facility, Centre of Excellence for Mass Spectrometry King’s College London. For the help on the LFQ experiment we want to thank F. Impens and D. van Haver from the VIB Proteomics Core. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Background: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). Methods: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. Results: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1–3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. Conclusions: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. Trial registration: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).
AB - Background: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). Methods: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. Results: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1–3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. Conclusions: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. Trial registration: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).
KW - Autologous hematopoietic stem cell transplantation
KW - Label-free quantification
KW - Multiple myeloma
KW - Oral mucositis
KW - Saliva
KW - TMT-labelled proteomics
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U2 - https://doi.org/10.1186/s12903-023-03190-w
DO - https://doi.org/10.1186/s12903-023-03190-w
M3 - Article
C2 - 37420206
SN - 1472-6831
VL - 23
SP - 1
EP - 17
JO - BMC Oral Health
JF - BMC Oral Health
IS - 1
M1 - 460
ER -