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. 2021 Jan 7;40:20. doi: 10.1186/s13046-020-01807-4

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Screen BACE2 as a candidate of csGRP78 downstream molecule. a Heat map shows the differential proteins acquired by mass spectrometry. Anti-GRP78 versus Isotype, blue indicates downregulation while red indicates upregulation. b mRNA profile distinguishes PN GBMs from MES GBMs in TCGA database. c Compared downregulated proteins in anti-GRP78 versus isotype with upregulated genes in MES-subtype GBMs, overlapping total 6 genes. d Statistical analysis for differential expression of these 6 candidates in mRNA profiling of MES and PN GSCs (GSE67089). e BACE2 mRNA expression in normal tissues, low-grade glioma (LGG) and GBM from TGCA database. f BACE2 mRNA expression in TCGA database grouped by subtype. g Survival curve and log-rank test for GBM patients stratified by the BACE2 expression from TCGA database. h GSEA indicates expression of BACE2 positively correlated with MES subtype, while negatively with PN subtype. i GSEA shows BACE2 has the strong correlation with NF-κB pathway. j Correlation between expression of BACE2 with selected MES and PN signatures in TCGA database. k Correlation analysis for expression of BACE2 and GRP78 in TCGA database. l western blot analysis for BACE2 in GSC11, 8–11,20 and 267. *p < 0.05, **p < 0.01, ***p < 0.001