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The endoplasmic reticulum stress marker CHOP predicts survival in malignant mesothelioma

Lookup NU author(s): Professor James WasonORCiD

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Abstract

Background: Mesothelioma is an incurable cancer originating from the mesothelial cells that line the pleural, peritoneal and pericardial cavities. These cells synthesise large quantities of surface glycoproteins, rendering them dependent upon efficient endoplasmic reticulum (ER) function. When faced with elevated levels of secretory protein load, cells are said to experience ER stress, which has been implicated in the pathogenesis of many human diseases including cancer.Method:We set out to measure markers of ER stress in malignant mesothelioma and to determine whether ER stress signalling correlates with clinical parameters.Results:We observed that expression of the ER stress-responsive transcription factor C/EBP homologous protein (CHOP) correlated with patient survival and remained an independent prognostic variable in pairwise comparisons with all clinical variables tested. The most parsimonious multivariate model in our study comprised only performance status and CHOP staining. In contrast, expression of the ER stress-responsive phosphatase growth arrest and DNA damage 34 (GADD34) correlated with the degree of mesothelial differentiation, being lost progressively in biphasic and sarcomatoid mesotheliomas.Conclusion:Our findings suggest that staining for CHOP provides prognostic information that may be useful in the stratification of patients with mesothelioma. Staining for GADD34 may prove useful in classification of mesothelioma histopathology. © 2013 Cancer Research UK. All rights reserved.

Publication metadata

Author(s): Dalton LE, Clarke HJ, Knight J, Lawson MH, Wason J, Lomas DA, Howat WJ, Rintoul RC, Rassl DM, Marciniak SJ

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2013

Volume: 108

Issue: 6

Pages: 1340-1347

Online publication date: 14/02/2013

Date deposited: 31/01/2018

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/bjc.2013.66

DOI: 10.1038/bjc.2013.66

PubMed id: 23412101

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