IRAK2, an immune and radiation-response gene, correlates with advanced disease features but predicts high post-irradiation local control in resected oral cancer patients

Abstract

Abstract Radiotherapy (RT) is an effective treatment modality for managing resected oral squamous cell carcinoma (OSCC) patients. The present study conducted gene ontology to explore the functional biological analysis of IRAK2 and performed case analysis to define its clinical role in disease progression and mediating tumor response to RT. Transcriptome sequencing data from the OML1 oral cancer cell line was analyzed to explore IR-responding genes. For identified significant IR-responsive genes, gene ontology (GO) analysis was conducted for exploring their involved bio-logical processes. From Jan. 2007 to Dec. 2014, 172 OSCC patients who received radical surgery with (n = 93) and without (n = 79) postoperative RT were identified for clinical validation. Their OSCC formalin-fixed paraffin-embedded histological samples were examined retrospectively to define IRAK2 expression. After irradiation treatments, IRAK2 upregulation was identified obviously suggesting its role as a potential radiation biomarker. Moreover, GO enrichment analysis showed IRAK2 involved ten of 14 top enriched post-irradiation biological processes, focusing on stress response and immune modulation in vitro. Clinically, high IRAK2 expression was correlated with several adverse disease features, including pT3-4 status (P = 0.01), advanced overall stage (P = 0.02), and positive bone invasion (P = 0.01). In patients who underwent RT, the IRAK2-high group was associated with fewer post-irradiation local recurrence (multivariate HR, 0.243; 95% CI, 0.071–0.838; P = 0.025) than the IRAK2-low group. However, the local control benefit did not translate into patient survival. On the other hand, for patients with no RT, IRAK2 did not predict local control. IRAK2 plays a crucial role in the radiation-induced response. In summary, patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control than those with low expression. These findings support IRAK2 as a potential predictive biomarker for RT response in OSCC patients. Further prospective clinical studies are encouraged.