title: Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer.
abstract: Colorectal cancer (CRC) is a major public health issue worldwide, and novel tumor markers may contribute to its efficient management by helping in early detection, prognosis or surveillance of disease. The aim of our study was to identify new serum biomarkers for CRC, and we followed a phased biomarker discovery and validation process to obtain an accurate preliminary assessment of potential clinical utility. We compared colonic tumors and matched normal tissue from 15 CRC patients, using two-dimensional difference gel electrophoresis (2D-DIGE), and identified 17 proteins that had significant differential expression. These results were further confirmed by western blotting for heat shock protein (HSP) 60, glutathione-S-transferase Pi, α-enolase, T-complex protein 1 subunit β, and leukocyte elastase inhibitor, and by immunohistochemistry for HSP60. Using mAbs raised against HSP60, we developed a reliable (precision of 5-15%) and sensitive (0.3 ng·mL(-1)) immunoassay for the detection of HSP60 in serum. Elevated levels of HSP60 were found in serum from CRC patients in two independent cohorts; the receiver-operating characteristic curve obtained in 112 patients with CRC and 90 healthy controls had an area under the curve (AUC) of 0.70, which was identical to the AUC of carcinoembryonic antigen. Combination of serum markers improved clinical performance: the AUC of a three-marker logistic regression model combining HSP60, carcinoembryonic antigen and carbohydrate antigen 19-9 reached 0.77. Serum HSP60 appeared to be more specific for late-stage CRC; therefore, future studies should evaluate its utility for determining prognosis or monitoring therapy rather than early detection.
authors.affiliation: Immunoproteomics Laboratory, Department of Biomarkers, bioMérieux, Marcy l'étoile, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Hamelin
authors.forename: Emilie
authors.initials: E
authors.lastname: Cornut
authors.forename: Florence
authors.initials: F
authors.lastname: Poirier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Pons
authors.forename: Corinne
authors.initials: C
authors.lastname: Beaulieu
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Charrier
authors.forename: Hader
authors.initials: H
authors.lastname: Haïdous
authors.forename: Eddy
authors.initials: E
authors.lastname: Cotte
authors.forename: Claude
authors.initials: C
authors.lastname: Lambert
authors.forename: Françoise
authors.initials: F
authors.lastname: Piard
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Ataman-Önal
authors.forename: Geneviève
authors.initials: G
authors.lastname: Choquet-Kastylevsky
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood; D015153:Blotting, Western; D018395:CA-19-9 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D018834:Chaperonin 60 / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D014408:Biomarkers, Tumor; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D018834:Chaperonin 60