Prognostic factors of atypical meningiomas treated with gross total resection and early radiotherapy: microRNA-221/222 co-modulated radiosensitivity regulatory mechanism and malignent progression

Background. The impact of adjuvant radiation therapy (XRT) after gross-total resection (GTR) of atypical meningiomas (AMs) has always been controversial. Considering that intrinsic differences among these AMs may exist, our study aim to seek which kind of these patients is more likely to recur and to explore its underlying causes. Methods. The case database and the pathological records of our hospital between Jan 2008 and Jul 2016 were reviewed, 46 AMs received early XRT after GTR (confirmed by the 2016 revision of WHO diagnostic criteria). Microarray analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect aberrant expression of microRNAs (miRs). Immunohistochemical staining for the biomarker was performed, and its expression was semi-quantitative analyzed by using Image Pro Plus (IPP) 6.0. Univariate and multivariate Cox proportional hazards regression analysis were used to assess the correlation between various factors and recurrence. Results. Microarray analysis and qRT-PCR demonstrated that miR-221/222 were upregulated in radiotherapy resistance (RTR) AM tissues compared with radiotherapy sensitive (RTS) AM tissues. Multivariable analysis showed that malignant progression (MP) (P=0.011), low expression level of PTEN (P=0.026) and skull-base AMs (P=0.028) were associated with higher recurrence. Conclusion. We first demonstrated that upregulated miR-221/222 could decrease the radiosensitivity of the combination-therapy-treated AMs. Meanwhile, AMs with low expression level of PTEN, skull-base located were more likely to recur. MP-AMs were associated with increased possibility of recurrence by comparing to primary AMs. Treatment and consideration of MP-meningiomas were advocated to refer to the therapeutic strategy for higher grade meningiomas rather than restricted to its present grade. Among these 46 AMs, 6 patients (13.0%) presented with recurrent tumours at the last follow-up. The median time of recurrence was 33.5 months. Patients with recurrence time shorter than 33.5 months were classified into Radiotherapy resistance group (RTR), while those with PFS longer than 33.5 months, regardless of recurrence, were classified into Radiotherapy sensitive group (RTS). 3 AMs from each group were selected. Their FFPE samples (from the surgery right before XRT) were applied. Microarray analysis and qRT-PCR were performed to detect aberrant expression of microRNAs.