Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer.
We have used a gene expression array-based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)-marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA-based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future.
Departments of Surgery, Oncology, and Pathology, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Sabine C
SC
Glöckner
Mashaal
M
Dhir
Joo Mi
JM
Yi
Kelly E
KE
McGarvey
Leander
L
Van Neste
Joost
J
Louwagie
Timothy A
TA
Chan
Wolfram
W
Kleeberger
Adriaan P
AP
de Bruïne
Kim M
KM
Smits
Carolina A J
CA
Khalid-de Bakker
Daisy M A E
DM
Jonkers
Reinhold W
RW
Stockbrügger
Gerrit A
GA
Meijer
Frank A
FA
Oort
Christine
C
Iacobuzio-Donahue
Katja
K
Bierau
James G
JG
Herman
Stephen B
SB
Baylin
Manon
M
Van Engeland
Kornel E
KE
Schuebel
Nita
N
Ahuja
D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D018938:Caco-2 Cells; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D019175:DNA Methylation / Q000502:physiology; D004252:DNA Mutational Analysis / Q000379:methods; D055088:Early Detection of Cancer; D005243:Feces / Q000737:chemistry*; D005260:Female; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D006023:Glycoproteins; C021240:tissue-factor-pathway inhibitor 2