Over-expression of cofilin-1 and phosphoglycerate kinase 1 in astrocytomas involved in pathogenesis of radioresistance.

Introduction: Astrocytoma is among the most common intracranial tumors and radiotherapy is typically used after its resection. One of the outstanding problems encountered in the treatment is radioresistance. The lack of efficient biomarkers for evaluating the radiosensitivity of glioma precludes advances in treatment of astrocytoma and remains the most fatal cancer.

Methods: To identify potential biomarkers for assessing the radioresistance of astrocytomas, the following study investigated the proteome of astrocytoma in surgical samples from 15 typical patients. The patients were divided into 2 groups: radioresistant vs. radiosensitive (controls). Proteome was assessed using two-dimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS). Western blot was adopted to confirm the differential expression of proteins.

Results: A total of 36 proteins were expressed differently between the 2 groups, represented by cofilin-1 and phosphoglycerate kinase 1 (PGK1), which up-regulated significantly in radioresistant astrocytomas though there was no obvious morphological change of tumors. Western blot analysis revealed elevated levels of protein extracts in radioresistant astrocytomas compared with the radiosensitive group.

Conclusions: The results indicated cofilin-1 enhances the motility of tumor cells which is important invasive potential of malignancy. PGK1 is metabolic enzyme and seems to be correlated with the negative prognosis following radiotherapy. Thus, cofilin-1 and PGK1 might be involved in the radioresistant phenotype and are potential biomarkers for developing better therapeutic methods.