The poor outcome of second primary oral squamous cell carcinoma is attributed to Bmi1 upregulation

Abstract

Radiotherapy for nasopharyngeal carcinoma has been reported to cause second primary oral squamous cell carcinoma (s-OSCC). The prognosis and pathologic characteristic of s-OSCC are largely unknown. Bmi1 was associated with the repair of radiation-induced DNA damage, suggesting its possible involvement in the pathologic process of s-OSCC. Herein, we compared the prognosis between s-OSCC and primary OSCC (p-OSCC) and explored the involvement of Bmi1 in s-OSCC development. In this retrospective study, s-OSCC and p-OSCC patients were matched by propensity scores. Their outcomes were compared by univariate and multivariate analyses. The expression of Bmi1 in s-OSCC and p-OSCC was detected by immunohistochemistry (IHC). Radiation-induced Bmi1 alteration in early-stage was explored in a rat model and HaCaT cells. After matching, 116 pairs of patients with highly balanced characteristics were included. In univariate analysis, the overall survival (OS), disease-specific survival (DSS), and local recurrence-free survival (LRFS) were poorer in s-OSCC than in p-OSCC (P < 0.05), while their regional metastasis-free survival (RMFS) was parallel (P = 0.112). Multivariate analysis further revealed that radiotherapy history was an independent risk factor for OS, DSS, and LRFS (P < 0.05). IHC results showed that the positive rate of Bmi1 was higher in s-OSCC (P = 0.0027). In a rat model of radiotherapy-induced mucositis, Bmi1 upregulation was observed 8 days after irradiation. Consistently, Bmi1 was upregulated in HaCaT cells 1 h after irradiation, and its upregulation was in accord with X-ray exposure duration. In conclusion, the prognosis of s-OSCC is poorer as compared to p-OSCC, which may be attributed to Bmi1 upregulation.

s-OSCC exhibits poorer OS, DSS, and LRFS as compared to p-OSCC. Bmi1 is upregulated in s-OSCC, as well as in early-stage alteration in a rat model and HaCaT cells, suggesting its possible involvement in s-OSCC initiation and progression.

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