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. 2022 Mar 28;23(7):3714.
doi: 10.3390/ijms23073714.

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren's Syndrome Patients

Håvard Hynne  1 , Lara A Aqrawi  1   2 , Janicke Liaaen Jensen  1 , Bernd Thiede  3 , Øyvind Palm  4 , Cecilie Delphin Amdal  5 , Kristine Løken Westgaard  1   6 , Bente Brokstad Herlofson  1   6 , Tor P Utheim  7   8 , Hilde Kanli Galtung  8
Affiliations

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren's Syndrome Patients

Håvard Hynne et al. Int J Mol Sci. .

Abstract

Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers.

Keywords: Sjögren’s syndrome; biomarkers; head-and-neck cancer; immune response; inflammation; lacrimal glands; meibomian glands; proteomics; radiotherapy; saliva; salivary glands; tear fluid; tissue healing.

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Conflict of interest statement

T.P.U. is co-founder and co-owner of The Norwegian dry eye clinic and The clinic of eye health, Oslo, Norway. He has served on the global scientific advisory board for Novartis and Alcon as well as the European advisory board for Shire Pharmaceuticals.

Figures

Figure 1
Figure 1
Heatmap of the over- (red) and under-expressed (green) proteins detected in whole saliva of radiated head and neck cancer patients vs. controls.
Figure 2
Figure 2
Heatmap of the over- (red) and under-expressed (green) proteins detected in whole saliva of primary Sjögren’s syndrome (pSS) patients vs. controls.
Figure 3
Figure 3
Heatmap of the over- (red) and under-expressed (green) proteins detected in whole saliva of radiated head and neck cancer patients vs. primary Sjögren’s syndrome patients (pSS).
Figure 4
Figure 4
Protein–protein interactions of the significantly up- and downregulated proteins in saliva from HNC patients. The interaction map of the upregulated proteins is shown in panel (a) and the map of the downregulated proteins in panel (b). The Search Tool for the Retrieval of Interacting Genes/Proteins (http://string-db.org/ (accessed on 10 January 2022) was used to generate the networks, where potential interactions of proteins with medium confidence are shown. The colour of the connecting lines indicates the type of evidence used in predicting the associations (light blue: known interactions from curated databases; pink: known interactions experimentally determined red gene fusion; green: predicted interactions from gene neighbourhood; red: predicted interactions from gene fusions; dark blue: predicted interactions from gene co-occurrence; yellow/green: protein–protein associations through text-mining extracted from the literature; black: protein–protein associations through co-expression; light purple: protein–protein associations through protein homology).
Figure 5
Figure 5
Heat map of the over- (red) and under-expressed (green) proteins detected in tear fluid of radiated head and neck cancer patients compared to the controls.
Figure 6
Figure 6
Protein-protein interactions of significantly up- and downregulated proteins in tear fluid from HNC patients. The interaction map of upregulated proteins is shown in panel (a), and the map of downregulated proteins in panel (b). The Search Tool for the Retrieval of Interacting Genes/Proteins (http://string-db.org (accessed on 10 January 2022)) was used to generate the networks, where potential interactions of proteins with medium confidence are shown. The colour of the connecting lines indicates the type of evidence used in predicting the associations (light blue: known interactions from curated databases, pink: known interactions experimentally determined red gene fusion, green: predicted interactions from gene neighbourhood, red: predicted interactions from gene fusions, dark blue: predicted interactions from gene co-occurrence, yellow/green: protein-protein associations through text-mining extracted from literature, black: protein-protein associations through co-expression, light purple: protein-protein associations through protein homology).
Figure 7
Figure 7
FunRich analysis delineating the up- and downregulated biological processes identified in patients radiated for head and neck cancer (HNC) when compared to the controls, and patients with primary Sjögren’s syndrome (pSS) when compared to controls. Biological processes were identified using FunRich database and FunRich version 3.1.3 (2017).
Figure 8
Figure 8
Graphical description of the study design. pSS: primary Sjögren’s syndrome patients; HNC: head and neck cancer patients; LC-MS: liquid chromatography–mass spectrometry. Copyright Emily Moschowits.
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