To develop a novel glioblastoma liquid biopsy through plasma lipidomics.

Despite aggressive treatment, glioblastoma always recurs because surviving tumor cells acquire new mutations, which can alter cellular metabolism, including that of lipids. Analysis of the lipidomic profile of the plasma of patients with glioblastoma can uncover a deeper understanding of tumor metabolism, while also facilitating the development of a novel liquid biopsy for the diagnosis and monitoring of the disease.

Thirty six patients with isocitrate dehydrogenase (IDH) wild type glioblastoma were prospectively enrolled and untargeted lipidomics was performed of patient plasma before and after surgery, as well as before and after concurrent chemoradiation. We examined changes in the levels of 472 metabolites at each stage of treatment. Principal component analysis was performed to examine relationships between the lipidomic profiles at different treatment stages, while multiple comparison testing was used to identify metabolites with diagnostic potential. 

Thirty lipids were identified as significantly increased following surgery, with linoleic acid, TG 54:6, and oleic acid were those with the highest variable of importance (VIP) scores, while CE 22:6 and TG 42:2 were the only two lipids that were significantly decreased following surgery. Three lipids were significantly increased after chemoradiation, including TG 42:1, TG 40:0, and TG 40:1, while TG 49:1 was the only lipid that was decreased. Principal component analysis demonstrates that the lipidomic profile prior to surgery is distinct from those after surgery, prior to chemoradiation, and after chemoradiation. 

Plasma lipidomics of patients with glioblastoma reveals multiple lipids as diagnostic biomarkers of tumor presence and treatment stages. The lipidome prior to tumor resection appears to be distinct from that during other treatment stages. These results may lead to the development of a novel liquid biopsy for glioblastoma.