Clinicopathological Significance of Autophagy-related Proteins and its Association With Genetic Alterations in Gliomas

Abstract

Aim: To investigate clinicopathological significance of autophagy and its association with genetic alterations in gliomas.

Materials and methods: The expression of three autophagy-related proteins, light chain-3 (LC3), beclin 1, and p62 was immunohistochemically analyzed in 32 low-grade gliomas and 65 high-grade gliomas.

Results: LC3, beclin 1, and p62 expression was positive in 70/94 (74%), 51/94 (54%) and 55/96 (57%) gliomas, respectively. High expression of LC3, beclin 1 and p62 was significantly more frequent in high-grade gliomas than in low-grade. Positive expression of LC3, beclin 1 and p62 were significantly positively correlated with overall survival, methylation of O⁶-methylyguanine-DNA methyltransferase (MGMT) promoter, mutations of isocitrate dehydrogenase 1 (IDH1) and telomerase reverse transcriptase (TERT) promoter, and 1p/19q co-deletion. Kaplan-Meier analyses revealed that LC3, p62 and autophagy status (positivity for at least two of the three proteins) were significantly associated with poorer survival.

Conclusion: Autophagy might be associated with the progression of glioma, particularly high-grade, and thus might be a useful prognostic factor in patients with glioma.

Keywords: Glioma; LC3; autophagy; beclin 1; genetic alterations; p62.