Researchers from the Lunenfeld-Tanenbaum Research Institute in Toronto used the Olink® Explore 3072 platform for high-throughput protein biomarker discovery to look for novel diagnostic markers for glioma. Gliomas are among the most malignant tumors, with a very poor prognosis, and early diagnosis is highly desirable to optimize treatment outcomes. Earlier diagnosis would not only improve current clinical management, but could also facilitate access of patients with earlier stages of the disease to clinical trials and help develop more effective therapies. In this study, Olink Explore was used to measure >3,000 proteins in the plasma of patients with multiple forms of glioma, using samples from patients with unrelated meningiomas as controls.
The Olink analysis revealed that 8 plasma proteins were increased in gliomas versus meningiomas (GFAP, NEFL, EDDM3B, PROK1, MMP3, CTRL, GP2, SPINT3), while 4 proteins were decreased (FABP4, ALDH3A1, IL-12B and OXT). The majority of these proteins have previously been shown to have some relationship with brain tumor biology, strengthening their credible relevance to this study. When the proteins were examined in the context of survival prediction, several showed nominal associations, but none reached statistical significance. The authors suggest that this is likely due to the low statistical power resulting from the low number of cases and death events in this relatively small study, and that larger follow-up investigations would be required to evaluate the prognostic value of these proteins.
To explore the diagnostic potential of these proteins, statistical modeling was then applied to assess their predictive value. The strongest performing individual protein was GFAP, with an area under the curve, AUC=0.86 while the combination of GFAP and FABP4 had AUC=0.98, discriminating gliomas from controls with extremely high accuracy. The conclusion was that these findings identified novel, putative diagnostic (and potentially prognostic) glioma markers that may prove valuable, when used alone or in combination, towards improved clinical care of gliomas. The authors also discuss this study in the context of their previous research using other technologies such as mass spectrometry and ELISAs, concluding that Olink’s PEA technology has many advantages and is a powerful proteomic technology for biomarker discovery.