IRAK2, an Immune and Radiation-Response Gene, Correlates with Advanced Disease Features but Predicts Higher Post-Irradiation Local Control in Non-Metastatic and Resected Oral Cancer Patients

Author:

Yu Chih-Chia12,Lin Hon-Yi23,Hsieh Chen-Hsi456ORCID,Chan Michael W. Y.78910ORCID,Chiou Wen-Yen23ORCID,Lee Moon-Sing23,Chi Chen-Lin11,Lin Ru-Inn2,Hsu Feng-Chun2ORCID,Chen Liang-Cheng23,Chew Chia-Hui23,Yang Hsuan-Ju2,Hung Shih-Kai23ORCID

Affiliation:

1. Department of Medical Research, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan

2. Department of Radiation Oncology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi 62247, Taiwan

3. School of Medicine, Tzu Chi University, Hualien 97004, Taiwan

4. Division of Radiation Oncology, Far Eastern Memorial Hospital, New Taipei City 220216, Taiwan

5. Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan

6. School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan

7. Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan

8. Epigenomics and Human Disease Research Center, National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan

9. Center for Innovative Research on Aging Society (CIRAS), National Chung Cheng University, Min-Hsiung, Chia-Yi 62102, Taiwan

10. Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

11. Department of Pathology, Chiayi Chang Gung Memorial Hospital, Chia-Yi 61363, Taiwan

Abstract

Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with 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 radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.

Funder

Dalin Tzu Chi Hospital

Buddhist Tzu Chi Medical Foundation

Ministry of Science and Technology, Taiwan

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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