Salivary inflammatory mediators as biomarkers for oral mucositis and oral mucosal dryness in cancer patients: A pilot study

Abstract

Oral mucositis (OM) is a common side effect in patients with cancer receiving chemotherapy and radiotherapy; however, no salivary mediator is known to be associated with OM. We aimed to determine candidate salivary inflammatory mediators potentially associated with OM in patients with cancer. To this end, we compared the relationships between OM grade, oral mucosal dryness, and inflammatory mediators (Interleukin (IL)-1β, IL-6, IL-10, IL-12p70, tumor necrosis factor (TNF), prostaglandin E2, and vascular endothelial growth factor) in patients with cancer and in healthy volunteers (HV). We collected saliva samples from 18 patients with cancer according to the following schedule: 1) within 14 days of treatment initiation, 2) within 3 days of OM occurrence, 3) when OM was improved or got worsened, and 4) within 7 days after chemotherapy completion. The oral care support team determined the OM grade at each sample collection point based on CTCAE version 5.0. Salivary inflammatory mediator concentrations were detected using cytometric bead array or enzyme-linked immunoassay. We compared oral mucosal dryness in pre- and post-index patients with cancer to that in HV (n = 33) using an oral moisture-checking device. Fourteen of eighteen patients experienced OM (four, grade 3 OM; four, grade 2 OM; six, grade 1 OM). IL-6, IL-10, and TNF salivary concentrations were significantly increased in the post-index group compared to those in the pre-index group (p = 0.0002, p = 0.0364, and p = 0.0160, respectively). Additionally, salivary IL-6, IL-10, and TNF levels were significantly higher in the post-index group than in the HV group (p < 0.0001, p < 0.05, and p < 0.05, respectively). Significant positive correlations were observed between OM grade and salivary IL-6, IL-10, and TNF levels (p = 0.0004, r = 0.4939; p = 0.0171, r = 0.3394; and p = 0007, r = 0.4662, respectively). Oral mucosal dryness was significantly higher in the HV than in the pre- and post-index groups (p < 0.001). Our findings suggest that salivary IL-6, IL-10, and TNF levels may be used as biomarkers for OM occurrence and grade in patients with cancer. Furthermore, monitoring oral mucosal dryness and managing oral hygiene before cancer treatment is essential.

Attempts to Understand Oral Mucositis in Head and Neck Cancer Patients through Omics Studies: A Narrative Review

“…The proteomic approach for OM research has focused on biomarker development, particularly on inflammatory proteins observed after treatment-induced OM. Kiyomi et al [36] utilized a bead array and an enzyme-linked immunosorbent assay (ELISA) to identify potential biomarkers of OM from saliva or oral swab samples were taken from 20 leukemia or head and neck cancer patients undergoing treatment. Their study suggests that salivary IL-6, IL-10, and TNF-α may serve as predictors of OM occurrence and grade.…”

Avaliação da relação entre mucosite oral e a expressão de citocinas inflamatórias séricas e salivares em pacientes submetidos ao transplante alogênico de células tronco hematopoiéticas

“…Foram avaliadas também, as citocinas em sangue e saliva para correlacionar com a gravidade da mucosite oral, o sangue apresentou correlação forte da expressão de TNF-α (ρ=0.403; p=0,009) em T0; e correlação moderada de TNF-α (ρ=0. 38 .…”