Use of oesophageal stress response proteins as potential biomarkers in the screening for Barrett's oesophagus.
BACKGROUND
Oesophageal adenocarcinoma is an increasingly common diagnosis and cause of death; risk factors include 'Barrett's epithelium' (BE). Endoscopic surveillance is most commonly used but is expensive. Other methods of surveillance have been suggested including nonendoscopic balloon cytology, but are handicapped by relying on cytological techniques; hence the need for a partner technology such as a biomarker. From earlier work we know the most commonly expressed oesophageal stress response proteins are SEP 53, SEP70 and anterior gradient-2 (AG-2). We set out to map the expression of these stress response proteins and explore their potential as prototype biomarkers of BE.


METHODS
Patients (n=192) presenting to the endoscopy unit of a large teaching hospital with symptoms of gastro-oesophageal reflux disease or a known BE were recruited, endoscopically examined and the biopsies obtained were examined for heat shock protein expression.


CONCLUSIONS
Normal controls and those with oesophagitis predominantly expressed SEP 53 (76.9/91.95%) and SEP 70 (79.48/89.65%). Although those with BE expressed AG-2; using this expression as a marker for BE, gives a sensitivity of 65.15% and specificity of 89.68% (positive predictive value of 76.78% and negative predictive value of 84.9%) and in gastro-oesophageal reflux disease a sensitivity of 65.15% and specificity of 90.80% (positive predictive value of 84.31% and negative predictive value of 77.45%). We confirmed that AG-2 is preferentially expressed in BE; suggesting its use would allow a screening tool with specificity of around 90%.
Groome
Maximillian
M
Gut Group, Ninewells Hospital and Medical School, University of Dundee, Scotland, UK. m.groome@nhs.net
Lindsay
Jamie
J
Ross
Peter E
PE
Cotton
James P
JP
Hupp
Ted R
TR
Dillon
John F
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005764:Gastroesophageal Reflux / Q000097:blood; D018840:HSP70 Heat-Shock Proteins / Q000097:blood; D006360:Heat-Shock Proteins / Q000097:blood*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009088:Mucoproteins; D009363:Neoplasm Proteins / Q000097:blood; D015513:Oncogene Proteins; D011230:Precancerous Conditions / Q000097:blood / Q000175:diagnosis*; D011506:Proteins / Q000032:analysis; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
C502296:AGR2 protein, human; D015415:Biomarkers; C418764:CRNN protein, human; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D009088:Mucoproteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011506:Proteins; C533662:SEP70 protein, human