Abstract
Background Radiotherapy is an important modality in treating head and neck cancers. Clinically, predicting radiation response is essential. Stem-like cancer cells have been reported as having a high degree of radiation resistance. However, whether stem cell markers, such as OCT4 and NANOG, can predict clinical outcomes in patients with resected-then-irradiated oral cancer is still unknown. Methods We established a radioresistant cell subline, OML1_R, from OML-1 oral cancer cells by using sequent 5-Gy irradiations, with a total dose of 50 Gy. Between each irradiation, cancer cells were allowed to regrow for 5–7 days, then PCR was used to detect mRNA expression of stem cell markers. Paraffin-embedded human tissue sections were used for validation of the role of stem cell markers in predicting post-resection, post-irradiation clinical outcomes. Findings A 10-Gy radiation stress test confirmed the radioresistance of OML1_R. PCR showed upregulation of OCT4 (4-fold) and NANOG (6-fold) in OML1_R cells compared with their parent OML-1 cells. In 44 patients with resected-but-close-margined oral cancer, higher locoregional control was observed in the low OCT4/NANOG expression group compared with the high OCT4/NANOG expression group (92% versus 62%, p = 0.03). Multivariate analysis confirmed that this stem cell marker is an independent factor in predicting locoregional control (adjusted hazard ratio 6.76; 95% confidence interval 1.87–24.43; p = 0.04). Interpretation Our data showed that stem cell markers OCT4 and NANOG are potential bio-predictors in patients with resected-then-irradiated oral cancer.
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