Background: Glioblastoma (GB) is a highly aggressive form of brain cancer with less than 5% of patients surviving for five years after diagnosis. Its etiology remains unclear and hence there is an unmet need to further investigate the underlying potential mechanisms of GB to identify novel treatment targets. More than 16% of cancer incidence worldwide has been attributed to infectious pathogens. Recent research has suggested that pathogens may play a role in the development of GB. Pathogens are known to cause cancer and are involved in several brain disorders. Studies have shown that patients with GB have higher levels of virus-specific antibodies, indicating past exposure to pathogens such as cytomegalovirus and Epstein-Barr virus, compared to healthy individuals. Furthermore, multiple studies have shown the presence of various pathogens in GB tissues, but however are limited to only one technology (DNA/RNA sequencing or immunohistochemistry).
Aim: To investigate the mechanisms underlying potential association between pathogens and glioblastoma by utilizing a multi-omics approach: bioinformatics, metagenomics, and proteomics.
Methods: Bioinformatic pathogen screening was performed using publicly available raw mass spectrometry data from 3 independent publications using our established data identification protocol. Additionally, whole genome metagenomics sequencing and tandem mass spectrometry proteomics analysis were performed on a cohort of 19 GB formalin-fixed paraffin embedded and fresh frozen core autopsy biopsies that were obtained from Hunter Cancer Biobank, Newcastle. The sample cohort includes 15 males, and 4 females with a median age of 60 years.
Results: Our pathogen screening of publicly available data suggest the presence of certain pathogens in GB samples. We hypothesize therefore that certain pathogen-derived gene products (proteins) may be implicated in the etiology of glioblastoma.
Conclusion: The information generated from this research may advance the current understanding of GB etiology. If further substantiated, the presence of viruses in GB could lead to the identification of new blood-based biomarkers, drive a new stratification of patient tumor types, and ultimately lead to the development of new treatments that improve the outcomes of patients with GB.