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

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

Induction of Collagenolytic MMP-8 and -9 Tissue Destruction Cascade in Mouth by Head and Neck Cancer Radiotherapy: A Cohort Study

“…Our findings support and further extend the earlier observations showing an increase in aMMP-8 levels and clinical attachment loss due to the RT in HNC patients [28]. In accordance with the present results, MMP-8 have been demonstrated to be upregulated in whole-saliva samples in radiated HNC patients compared to healthy controls [29]. Active MMP-8 levels and the neutrophil/lymphocyte ratio have been shown to increase in the first three weeks of HNC RT, suggesting inflammation both locally and systemically [26].…”

“…MPO and TIMP-1 have been previously demonstrated to be downregulated proteins in tear fluid from radiated HNC patients compared to controls [29]. Our results showed the down-trending curve of TIMP-1 levels but an opposite trend for MPO.…”

Tear film proteome changes following Tobradex® therapy in anterior blepharitis

“…When released from cells, histones can trigger inflammatory responses as key components of neutrophil extracellular traps or by activating the nucleotide‐binding domain, leucine‐rich repeat containing protein 3 (NLRP3) inflammasome (Hoeksema et al., 2016; Huang et al., 2013). Increased levels of histone proteins have previously been identified in tear fluid samples from patients with head and neck cancer who received radiotherapy where histone proteins are thought to trigger inflammatory responses (Hynne et al., 2022). Thus, an anti‐inflammatory role through downregulation of histone proteins may be considered for Tobradex ® intervention.…”

Tear Proteomics Approach to Distinguishing Primary from Secondary Sjögren’s Syndrome for Dry Eye Patients with Long-Term Instillation of Eyedrops

“…ADAM10 has also been identified in a corneal model of epithelial resurfacing [ 23 ]. Immune responses may lead to tissue damage, followed by wound repair [ 24 ]. According to the Oxford staining score of our patients, which is a scheme used to estimate surface damage in dry eye, results showed a significantly increasing proportion of patients with more severe grading from the non-SS-DED group to the sSS-DED group ( Table 1 ).…”

“…In pSS patients versus controls, protein metabolism was found to be a significantly upregulated biological process, involving MMP8, SERPINB5, RPLP2, CSTB, and CST3, etc. [ 24 ]. Our results also showed protein synthesis as the top associated functional pathway according to IPA analysis.…”