(WHS-P3.06) TRANSCRIPTOMIC PREDICTORS OF ORAL MUCOSITIS SEVERITY IN HEAD AND NECK CANCER PATIENTS
Friday, May 17, 2024
10:30 AM – 11:30 AM East Coast USA Time
Background: A common side effect of radiation therapy for head and neck cancer (HNC) is oral mucositis (OM), characterized by erythema, edema, and ulcers. Severe OM affects more than two-thirds of HNC patients, which can lead to malnutrition, dehydration, and risk of infection. Preliminary evidence suggests the role of transcriptome changes in pain heterogeneity associated with OM, but the literature lacks evidence if transcriptomic factors play a role in the development and worsening of OM. The present study aimed to identify differentially expressed genes (DEGs) before cancer treatment (baseline) that may be associated with the worsening of OM during radiation therapy (RT), and 2) to determine the gene sets associated with the identified DEGs.
Methods: This is a sub-analysis of a clinical trial (ARMOR-Trial NCT03843554), where HNC patients who were expected to receive at least 5000 cGy of RT to the oral or oropharyngeal mucosa were recruited. This study used data from 26 participants in a control group that received regular oral care. Total RNA extracted from whole blood at baseline (before RT) was subjected to RNA-seq analysis. Based on changes in OM severity from baseline to RT completion assessed by the World Health Organization’s Oral Toxicity Scale, the participants were classified into mucositis (change ≧ 1, n = 20) or no mucositis groups (change < 1, n = 6). DEGs were identified between the two groups with a p-value < 0.05 and |log2 fold change| > 1. Gene Set Enrichment Analysis (GSEA) determined gene sets associated with the identified DEGs.
Results: A total of 161 (132 upregulated and 29 downregulated) DEGs were identified. GSEA showed 13 activated biological processes, including “peptide metabolic process (normalized enrichment score (NES) = 1.73, p = .006),” “regulation of hormone levels (NES = 1.76, p = .008),” and “homeostatic process (NES = 1.58, p = .045).” GSEA also showed four activated and one suppressed molecular function, including activated “cytokine activity (NES = 1.78, p = .007)” and suppressed “enzyme binding (NES = -1.94, p = .003),” and four activated and one suppressed cellular components, including activated “bounding membrane of organelle (NES = 1.74, p = .015)” and suppressed “somatodendritic compartment (NES = -1.71, p = .023).”
Conclusions: We profiled the transcriptomic signatures before RT that are related to worsening OM severity in HNC patients. The GSEA suggested that some homeostasis-related biological activities, including metabolism, hormone regulation, and cytokine activities were associated with the worsening of OM in this population, which is informative for further investigations.