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Explorative study of stimulated saliva proteome in head and neck cancer patients pre-and post-treatment

ABSTRACT: Abstract Objectives: to compare saliva proteome of head and neck cancer patients prior to treatment and six months post-treatment with that of controls and relate the level of mucins with patient’s problems with dry mouth, sticky saliva and swallowing. Design: Five dentate patients and five age and gender matched controls were included. The stimulated salivary secretion rate was determined and saliva stored at -80°C. After thawing, 30 mg of each sample and a reference was trypsin digested. The digested peptides were analyzed by mass spectrometry. The relative abundances were transformed to log2 and significant differences determined. Relative abundances of mucins were compared with patient’s problems with dry mouth, sticky saliva and swallowing. Results: 966 proteins with ≥ 2 unique peptides were found. Compared with controls, 21 proteins were found in lower relative abundances and 30 in higher at pre-treatment and 28 proteins in lower relative abundances and 24 proteins in higher post-treatment. Regarding saliva proteins, a lower relative abundance of Cystatins was detected pre-treatment and lower relative abundances of Cystatin, Cysteine-rich secretory protein 3, Lactoperoxidase, Prolactin-inducible protein and Proline-rich protein 4 post-treatment. No clear relation between mucins and dry mouth, sticky saliva and problems with swallowing was detected. Conclusion: Decreases in several saliva proteins post cancer treatment might lead to a reduced defense against oral disorders. Knowledge about changes in saliva proteins in connection with oral cancer treatment is important for planning dental care for these patients.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

DISEASE(S): Brain Cancer

SUBMITTER: Johannes Fuchs

LAB HEAD: Annica Almståhl

PROVIDER: PXD047500 | Pride | 2024-10-14

REPOSITORIES: Pride

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			Action	DRS
	4349_1FRDPeptide5Protein_Lumos220124_8to23_220202.xlsx	Xlsx
	4349_TMTpro16pl_0MC_65SPS_Norm_Human_Lumos220124_8to23_.msf	Msf
	4349_TMTpro16pl_0MC_65SPS_Norm_Human_Lumos220124_8to23_.pdResult	Other
	Lumos_220124_08.raw	Raw
	Lumos_220124_09.raw	Raw

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Project description:Sjogren’s syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tears and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Altered pathways in SS patients’ tears included leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation. In healthy controls’ tears, enriched proteins for glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients’ saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls’ saliva, enriched proteins for JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein previously shown to be present in tears and never studied in saliva, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients’ tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings improve our mechanistic understanding of the disease and changes in SS patients’ protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.

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Explorative study of stimulated saliva proteome in head and neck cancer patients pre-and post-treatment

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