# Surface Proteomic Analysis Reveals the Presence of Noncanonical Cell Membrane Endoplasmic Reticulum Chaperones in High-Grade Gliomas

## TL;DR

This study finds that certain ER chaperones, typically found inside cells, are present on the surface of aggressive brain tumors, suggesting new potential treatment targets.

## Contribution

The study is the first to analyze surface expression of ER chaperones in both adult and pediatric high-grade gliomas.

## Key findings

- Surface expression of ER chaperones in high-grade gliomas differs from non-neoplastic samples.
- There is poor correlation between mRNA, total protein, and surface protein levels of ER chaperones.
- Ectopically expressed ER chaperones are often missed by conventional bioinformatic methods.

## Abstract

High-grade gliomas
(HGG) are highly aggressive tumors,
which are
predominately fatal for adults and pediatric patients. Identifying
cancer-selective therapeutic targets remains a critical unmet need.
The overexpression of endoplasmic reticulum (ER) chaperones in various
cancers is well documented. Moreover, tumor cells exhibit an atypical
surface expression of ER chaperones, suggesting the potential for
selective targeting. Our study examined the differences in the mRNA,
total protein, and surface expression levels of seven key ER chaperones,
compared with those in non-neoplastic samples. Notably, a poor correlation
was found between mRNA, protein, and surface protein levels, underscoring
the limitations of transcriptomics alone in target discovery. We also
highlight the limitations of surfaceome studies which exclude noncanonical
membrane proteins, such as ectopically expressed ER chaperones, which
often escape detection by conventional bioinformatic pipelines. For
the first time, this study advances our understanding of the surface
expression of ER chaperones in both adult and pediatric HGG. Our findings
highlight the importance of surfaceome analysis in the discovery of
cancer selective targets against this devastating disease.