Human Endogenous Retroviruses in Glioblastoma Multiforme

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor. It is primarily diagnosed in the elderly and has a 5-year survival rate of less than 6% even with the most aggressive therapies. The lack of biomarkers has made the development of immunotherapy for GBM challenging. Human endogenous retroviruses (HERVs) are a group of viruses with long terminal repeat (LTR) elements, which are believed to be relics from ancient viral infections. Recent studies have found that those repetitive elements play important roles in regulating various biological processes. The differentially expressed LTR elements from HERVs are potential biomarkers for immunotherapy to treat GBM. However, the understanding of the LTR element expression in GBM is greatly lacking. Methods: We obtained 1077.4 GB of sequencing data from public databases. These data were generated from 111 GBM tissue studies, 30 GBM cell lines studies, and 45 normal brain tissues studies. We analyzed repetitive elements that were differentially expressed in GBM and normal brain samples. Results: We found that 48 LTR elements were differentially expressed (p-value < 0.05) between GBM and normal brain tissues, of which 46 were HERV elements. Among these 46 elements, 34 significantly changed HERVs belong to the ERV1 superfamily. Furthermore, 43 out of the 46 differentially expressed HERV elements were upregulated. Conclusion: Our results indicate significant differential expression of many HERV LTR elements in GBM and normal brain tissues. Expression levels of these elements could be developed as biomarkers for GBM treatments.