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Aims: Evaluate the abundance of the selected targets, alpha-1-antitrypsin (A1AT) and macrophage migration inhibitory factor (MIF), and correlate these findings with the risk of developing severe oral mucositis (OM).

Materials and Methods: Head and Neck squamous cell carcinoma (HNSCC) patients submitted to RT or chemo-radiotherapy (CRT) were assessed. OM grade and pain were evaluated daily during the treatments. Two protein targets, A1AT and MIF, were evaluated, using selected reaction monitoring mass spectrometry (SRM-MS), in whole saliva, collected prior to oncologic treatment. The results obtained from the targeted proteomic analysis were correlated with OM clinical outcomes.

Results: A total of 27 patients were included, of whom 21 (77.8%) had locally advanced disease (clinical stage III or IV). Most patients (70.4%) received CRT. OM grade 2 (40.8%) and 3 (33.3%) were the most prevalent during RT with a mean highest reported OM-related pain of 3.22 through the visual analogue scale (VAS). The abundance of A1AT and MIF correlated significantly with severe (grade 3 or 4, p< 0.02) compared to moderate-low (grade 1 or 2, p< 0.04) OM grade.

Conclusions: There is a correlation between the abundance of salivary A1AT and MIF and oncologic treatment induced OM. The correlation of MIF expression with severe OM appears to be compatible with its physiological pro-inflammatory role. These results open up great possibilities for the use of changes in salivary MIF and A1AT levels as prognostic markers for effective therapeutic interventions, such as photobiomodulation therapy.