Su Il Kim1, Seon Rang Woo1, Joo Kyung Noh2, Min Kyeong Lee2, Young Chan Lee1, Jung Woo Lee3, Moonkyoo Kong4, Seong-Gyu Ko5, Young-Gyu Eun6,7. 1. Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 02447, Korea. 2. Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea. 3. Department of Oral and Maxillofacial Surgery, School of Dentistry, Kyung Hee University, Seoul, Korea. 4. Department of Radiation Oncology, Division of Lung & Head and Neck Oncology, Kyung Hee University Medical Center, Seoul, Korea. 5. Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea. 6. Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, #1 Hoegi-dong, Dongdaemun-gu, Seoul, 02447, Korea. ygeun@khu.ac.kr. 7. Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Korea. ygeun@khu.ac.kr.
Abstract
BACKGROUND: Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. METHODS: To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). RESULTS: Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (-) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. CONCLUSION: The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (-) status who were classified in more detail.
BACKGROUND: Various cancer stem cell (CSC) biomarkers and the genes encoding them in head and neck squamous cell carcinoma (HNSCC) have been identified and evaluated. However, the validity of these factors in the prognosis of HNSCC has been questioned and remains unclear. In this study, we examined the clinical significance of CSC biomarker genes in HNSCC, using five publicly available HNSCC cohorts. METHODS: To predict the prognosis of patients with HNSCC, we developed and validated the expression signatures of CSC biomarker genes whose mRNA expression levels correlated with at least one of the four CSC genes (CD44, MET, ALDH1A1, and BMI1). RESULTS: Patients in The Cancer Genome Atlas (TCGA) HNSCC cohort were classified into CSC gene expression-associated high-risk (CSC-HR; n = 285) and CSC gene expression-associated low-risk (CSC-LR; n = 281) subgroups. The 5-year overall survival and recurrence-free survival rates were significantly lower in the CSC-HR subgroup than in the CSC-LR subgroup (p = 0.04 and 0.02, respectively). The clinical significance of the CSC gene expression signature was validated using four independent cohorts. Analysis using Cox proportional hazards models showed that the CSC gene expression signature was an independent prognostic factor of non-oropharyngeal HNSCC which mostly indicates HPV (-) status. Furthermore, the CSC gene expression signature was associated with the prognosis of HNSCC patients who received radiotherapy. CONCLUSION: The CSC gene expression signature is associated with the prognosis of HNSCC and may help in personalized treatments for patients with HNSCC, especially in cases with HPV (-) status who were classified in more detail.
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