MSACL 2019 EU Abstract

The Predictive Potential of Salivary Proteomics for Characterization of the Phases of Allogeneic Hematopoietic Stem Cell Transplants

Milena Monteiro de Souza (1,4), Fabiana Martins de Paula (2), Marcelo Andreetta Corral (2), Claudia Malheiros Coutinho-Camillo (1), Silvia Vanessa Lourenço (3).
(1) International Research Center, A.C.Camargo Cancer, Sao Paulo, Brazil (2) Department of Infectious and Parasitic Diseases, School of Medicine, Hospital das Clínicas, University of São Paulo, Brazil (3) Department of General Pathology, Dental School, University of São Paulo, Brazil (4) Department of Dermatology, School of Medicine, University of São Paulo, Sao Paulo, Brazil

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Milena Souza (Presenter) International Research Center, A.C.Camargo Cancer

Presenter Bio: Bachelor's degree in Chemistry, PhD in Sciences by the Dermatology program of the Faculty of Medicine of the University of São Paulo in 2017. Currently postdoctoral fellow at the A.C. Camargo Cancer Center, Department of Investigative Pathology, working in the area of biomarkers in salivary gland tumors. Experience in Chemistry, with emphasis in Biochemistry working mainly in the following areas: Mass Spectrometry, electrophoresis, proteomics, salivary gland and neoplasias.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

Introduction: For the past 60 years, the hematopoietic stem cell transplant (HSCT) has been successfully used as standard therapy for hematological disorders. After conditioning therapy, patients undergoing allogeneic HSCT present three phases of engraftment that occurs in different time points. The Pre-engraftment phase is defined by severe neutropenia, the next phase called engraftment occurs in the first 100 days after HSCT characterized by cellular immunodeficiencies and in the Post-engraftment phase the patients undergo an immune reconstitution of T cells, which normally occurs around 100 days or can take up to 2 years after allogeneic HSCT. Severe complications are associated with morbidity, mortality and malignances after allogeneic HSCT, which include effects in the oral cavity.
Objectives: The changes in the salivary composition after HSCT may contribute to identify additional specific tools that could indicate early prognostic factors. Here, we focused on the relationship between the differential protein expression and the progression of allogeneic HSCT.
Methods: Unstimulated whole saliva collected from patients undergoing allogeneic HSCT (n=20) in three time points, were analyzed by a LC/MS-MS. All proteomic data were correlated with the phases after HSCT and were subjected to bioinformatics analysis. Furthermore, we also analyzed the gene ontology terms, PANTHER and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment.
Results: To investigate the differences in the salivary proteins samples of the three groups, we clustered via Heatmap and profile plot (based on their proteins expression). The analysis revealed that the proteins involved in regulation of body fluids are the proteins with major variation among each phase and were classified in different molecular functions. The heatmap showed that in the pre-engraftment phase Alpha-2-macroglobulin, 78kDa glucose-regulated protein, Peptidyl-prolyl cis-trans isomerase, Fibrinogen gamma chain, Kininogen 1, Glucose-6-phosphate isomerase, Hemoglobin subunit beta and alpha-1-antrypsin proteins were differently expressed. A group of six proteins, including Apolipoprotein A-1, Profilin-1, A2M, HSPA5, HBB and SERPINA 1, showed different abundance in engraftment phase. In post-engraftment phase, higher abundance of FGG, Alpha-actinin-4, Clusterin, Fructose-biphosphate aldolase and Myeloblastin was observed.
Conclusion: In the current study, we found that the global nature of saliva proteomics also allows us to quickly assess the quality of group samples and entire studies based on disease progression focusing on innate immune response in mucosa, mucosal immune response and regulation of body fluids levels. Furthermore, we successfully measured proteins and possible biomarkers with potential application for targeted therapeutics, a promising future approach to risk stratification and better disease treatment modalities.