Detection of methylated SEPT9 in plasma is a reliable screening method for both left- and right-sided colon cancers.
BACKGROUND
Methylated Septin 9 (SEPT9) is a sensitive biomarker for colorectal cancer (CRC) from peripheral blood. However, its relationship to cancer localization, guaiac-based fecal occult blood test (gFOBT) and carcinoembryonic antigen (CEA) have not been described.


RESULTS
Plasma samples were collected for SEPT9 analysis from patients with no evidence of disease (NED) (n=92) before colonoscopy and CRC (n=92) before surgical treatment. DNA was isolated and bisulfite-converted using Epi proColon kit 2.0. Qualitative determination was performed using Epi proColon 2.0 RT-PCR assay. Samples for gFOBT and CEA analysis were collected from NED (n=17 and 27, respectively) and CRC (n=22 and 27, respectively). SEPT9 test was positive in 15.2% (14/92) of NED and 95.6% (88/92) of CRC, including 100% (67/67) from stage II to stage IV CRC and 84% (21/25) of stage I CRC when a sample was called positive if 1 out of 3 PCR replicates was positive. In a second analysis (2 out of 3 PCR replicates) specificity improved to 99% (91/92) of NEDs, at a sensitivity of 79.3% (73/92) of SEPT9 positives in CRC. gFOBT was positive in 29.4% (5/17) of NED and 68.2% (15/22) of CRC and elevated CEA levels were detected in 14.8% (4/27) of NED and 51.8% (14/27) of CRC. Both SEPT9 (84.8%) and CEA (85.2%) showed higher specificity than gFOBT (70.6%). SEPT9 was positive in 96.4% (54/56) of left-sided colon cancer (LSCC) cases and 94.4% (34/36) of right-sided colon cancer (RSCC) cases. gFOBT was positive in 83.3% (10/12) of cases with LSCC and 50% (5/10) of cases with RSCC, elevated CEA was detected 60% (9/15) of LSCC and 41.7% (5/12) of RSCC.


CONCLUSIONS
The high degree of sensitivity and specificity of SEPT9 in plasma makes it a better method to detect CRC than gFOBT and CEA, even for the more difficult to detect RSCC.
2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary. drtothkinga@yahoo.com
Kinga
K
Tóth
Ferenc
F
Sipos
Alexandra
A
Kalmár
Arpád V
AV
Patai
Barnabás
B
Wichmann
Robert
R
Stoehr
Henriette
H
Golcher
Vera
V
Schellerer
Zsolt
Z
Tulassay
Béla
B
Molnár
D000368:Aged; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006138:Guaiac; D006801:Humans; D008297:Male; D008875:Middle Aged; D009780:Occult Blood; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D058112:Septins / Q000097:blood* / Q000235:genetics* / Q000378:metabolism*
D002272:Carcinoembryonic Antigen; D006138:Guaiac; C474315:SEPTIN9 protein, human; D058112:Septins