title: The endoplasmic reticulum stress marker CHOP predicts survival in malignant mesothelioma.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Division of Respiratory Medicine, Department of Medicine, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors: L E
authors: LE
authors: Dalton
authors: H J
authors: HJ
authors: Clarke
authors: J
authors: J
authors: Knight
authors: M H
authors: MH
authors: Lawson
authors: J
authors: J
authors: Wason
authors: D A
authors: DA
authors: Lomas
authors: W J
authors: WJ
authors: Howat
authors: R C
authors: RC
authors: Rintoul
authors: D M
authors: DM
authors: Rassl
authors: S J
authors: SJ
authors: Marciniak
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005260:Female; D005500:Follow-Up Studies; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008654:Mesothelioma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D015398:Signal Transduction; D015996:Survival Rate; D046888:Tissue Array Analysis; D051742:Transcription Factor CHOP / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C497249:DDIT3 protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1