Molecular classification of Crohn's disease and ulcerative colitis patients using transcriptional profiles in peripheral blood mononuclear cells.
Ulcerative colitis (UC) and Crohn's disease (CD) are common inflammatory bowel diseases producing intestinal inflammation and tissue damage. Although emerging evidence suggests these diseases are distinct, approximately 10% of patients remain classified as indeterminate inflammatory bowel disease even after invasive colonoscopy intended for diagnosis. A molecular diagnostic assay using a clinically accessible tissue would greatly assist in the classification of these diseases. In the present study we assessed transcriptional profiles in peripheral blood mononuclear cells from 42 healthy individuals, 59 CD patients, and 26 UC patients by hybridization to microarrays interrogating more than 22,000 sequences. Supervised analysis identified a set of 12 genes that distinguished UC and CD patient samples with high accuracy. The alterations in transcript levels observed by microarray were verified by real-time polymerase chain reaction. The results suggest that a peripheral blood mononuclear cell-based gene expression signature can provide a molecular biomarker that can complement the standard diagnosis of UC and CD.
Burczynski
Michael E
ME
Molecular Profiling and Biomarker Discovery/Biomarker Laboratory, Wyeth Research, 500 Arcola Rd., Collegeville PA 19426, USA. mburczynski@wyeth.com
Peterson
Ron L
RL
Twine
Natalie C
NC
Zuberek
Krystyna A
KA
Brodeur
Brendan J
BJ
Casciotti
Lori
L
Maganti
Vasu
V
Reddy
Padma S
PS
Strahs
Andrew
A
Immermann
Fred
F
Spinelli
Walter
W
Schwertschlag
Ulrich
U
Slager
Anna M
AM
Cotreau
Monette M
MM
Dorner
Andrew J
AJ
D000328:Adult; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000175:diagnosis*; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis*; D020869:Gene Expression Profiling; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D025202:Molecular Diagnostic Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods