Joo Kyung Noh1, Seon Rang Woo2, Miyong Yun3, Min Kyeong Lee1, Moonkyoo Kong4, Soonki Min4, Su Il Kim2, Young Chan Lee2, Young-Gyu Eun5,2, Seong-Gyu Ko6. 1. Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Republic of Korea. 2. Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, Seoul, Republic of Korea. 3. Department of Bioindustry and Bioresource Engineering, College of Life Sciences, Sejong University, Seoul, Republic of Korea. 4. Department of Radiation Oncology, Kyung Hee University Medical Center, Seoul, Republic of Korea. 5. Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Republic of Korea; ygeun@khu.ac.kr. 6. Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
Abstract
BACKGROUND: We propose a novel prognostic biomarker-based strategy for increasing the efficacy of radiotherapy (RT) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We identified genes associated with superoxide dismutase 2 (SOD2) and nuclear factor erythroid-2-related factor 2 (NRF2) from gene-expression data of The Cancer Genome Atlas (TCGA) by calculating Pearson correlation. Patients were divided into two groups using hierarchical clustering. Colony-formation assay was performed to determine radioresistance in HNSCC cell line CAL27. Pathway analysis was conducted using The Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: We developed a 49-gene signature with SOD2- and NRF2-associated genes. Using mRNA expression data for the 49-gene signature, we performed hierarchical clustering to stratify patients into two subtypes, subtype A and B. In the TCGA cohort, subgroup A demonstrated a better prognosis than subgroup B in patients who received RT. The signature robustness was evaluated in other independent cohorts. We showed through colony-formation assay that depletion of SOD2 or NRF2 leads to increased radiosensitivity. CONCLUSION: We identified and validated a robust gene signature of SOD2- and NRF2-associated genes in HNSCC and confirmed their link to radioresistance using in vitro assay, providing a novel biomarker for the evaluation of HNSCC prognosis. Copyright
BACKGROUND: We propose a novel prognostic biomarker-based strategy for increasing the efficacy of radiotherapy (RT) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We identified genes associated with superoxide dismutase 2 (SOD2) and nuclear factor erythroid-2-related factor 2 (NRF2) from gene-expression data of The Cancer Genome Atlas (TCGA) by calculating Pearson correlation. Patients were divided into two groups using hierarchical clustering. Colony-formation assay was performed to determine radioresistance in HNSCC cell line CAL27. Pathway analysis was conducted using The Database for Annotation, Visualization and Integrated Discovery (DAVID). RESULTS: We developed a 49-gene signature with SOD2- and NRF2-associated genes. Using mRNA expression data for the 49-gene signature, we performed hierarchical clustering to stratify patients into two subtypes, subtype A and B. In the TCGA cohort, subgroup A demonstrated a better prognosis than subgroup B in patients who received RT. The signature robustness was evaluated in other independent cohorts. We showed through colony-formation assay that depletion of SOD2 or NRF2 leads to increased radiosensitivity. CONCLUSION: We identified and validated a robust gene signature of SOD2- and NRF2-associated genes in HNSCC and confirmed their link to radioresistance using in vitro assay, providing a novel biomarker for the evaluation of HNSCC prognosis. Copyright
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