Advanced molecular characterization using Digital Spatial Profiling Technology on immuno-oncology targets in methylated compared with unmethylated IDH-wildtype glioblastoma

Autor: Jing Jing Gong, Yan Liang, Aled R. Daniels, Kathreena M Kurian, Yuqi Ren, Beatrice Lander, Antonis Tofias, Paul D. White, Xing Ren, Hannah Barber
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Neuro Oncol
Journal of Oncology
Journal of Oncology, Vol 2021 (2021)
Barber, H, Tofias, A, Lander, B, Daniels, A, Gong, J, Ren, Y, Ren, X, Liang, Y, White, P & Kurian, K M 2021, ' Advanced molecular characterization using Digital Spatial Profiling Technology on immuno-oncology targets in methylated compared with unmethylated IDH-wildtype glioblastoma ', Journal of Oncology, vol. 2021, 8819702 . https://doi.org/10.1155/2021/8819702
ISSN: 1687-8450
1687-8469
DOI: 10.1155/2021/8819702
Popis: Introduction. Glioblastoma (GBM) is the most common primary adult brain tumour with a median overall survival (OS) of 12–15 months. Molecular characterization of multiple immunooncology targets in GBM may help target novel immunotherapeutic strategies. We used NanoString GeoMx® Digital Spatial Profiling (DSP) to assess multiple immunooncology protein targets in methylated versus unmethylated IDH-wild-type glioblastoma. Methods. NanoString GeoMx® DSP technology uses multiple primary antibodies conjugated to indexing DNA oligos with a UV photocleavable linker. Tissue regions of interest (ROIs) are selected with bound fluorescent antibodies; oligos are released via a UV-mediated linker and quantitated. We used DSP multiplex analysis of 31 immunooncology proteins and controls (CD4, CD14, CD68, CD8A, B7-H3, PD-L1, CD19, FOXP3, CD44, STAT3 (phospho Y705), CD45, Pan Cytokeratin, MS4A1/CD20, CD45RO, PD1, CD3, beta-2 microglobulin, VISTA, Bcl2, GZMB, PTEN, beta-catenin, CD56, Ki-67, STAT3, AKT, p-Akt, S6, Histone H3, IgG Rabbit control, and Mouse IgG control) from ROIs in a cohort of 10 IDH-wild-type glioblastomas (5 methylated and 5 unmethylated). An nCounter platform allowed quantitative comparisons of antibodies between ROIs in MGMT methylated and unmethylated tumours. Mean protein expression counts between methylated and unmethylated GBM were compared using technical and biological replicates. Results. The analysis showed 10/27 immunooncology target proteins were significantly increased in methylated versus unmethylated IDH-wild-type glioblastoma tumour core (false discovery rate (FDR) Conclusions. NanoString GeoMx® DSP was used to analyse multiple immunooncology protein target expression in methylated versus unmethylated IDH-wild-type glioblastoma. In this small study, there was a statistical increase in CD4, CD14, CD68, CD8A, B7-H3, PDL-1, CD19, FOXP3, CD44, and STAT3 protein expression in methylated versus unmethylated GBM tumour core; however, this requires larger cohort validation. Advanced multiplex immunooncological biomarker analysis may be useful in identifying biomarkers for novel immunotherapeutic agents in GBMs.
Databáze: OpenAIRE
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