Systematic Evaluation of Paired Primary and Recurrent Gliomas Identifies Key Genetic Markers for Survival and Therapeutic Targets

Background: The differences in genetic characteristics between primary and recurrent gliomas have been poorly characterized. We investigated whether genetic characteristics in recurrent gliomas would differ from those of primary gliomas, as a means of identifying unique markers in recurrent glioma to permit a better understanding of disease progression and therapeutic considerations.   Methods: Multiple genes involved in eight important pathways in primary and their corresponding paired recurrent glioma samples from 42 patients were analyzed by immunohistochemical staining.   Findings: In recurrent glioma, we saw a significantly increased expression of PD-1, PD-L1, VEGF, VEGFR2, CD133, MGMT, and Rad51 when compared with their corresponding primary tumors. VEGF expression was correlated with VEGFR2 expression in both primary and recurrent gliomas, and their co-expression was associated with shorter progression-free survival (PFS) and overall survival (OS). PD-1 expression was correlated with PD-L1 expression in recurrent gliomas. As compared to primary gliomas, the overall expression of MGMT was increased in the adjuvant therapy group but was not statistically different from the no-adjuvant therapy group. The group in which MGMT increased had a shorter PFS and OS than did the group in which MGMT was not increased. Co-expression of P53 and Ki-67 in recurrent gliomas was associated with poor median OS after second resection. Interpretation: The gene expression characteristics of recurrent gliomas were significantly different from those of their corresponding primary gliomas, a result that has important implications for patient survival. Treatment based on these newly identified changes may offer better therapeutic options for recurrent glioma. Funding Statement: This work was surported by the National Natural Science Foundation of China (81572952). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement:  This study was approved by the Ethics Committee of SAHZU, and was carried out in accordance with the Declaration of Helsinki.