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Detection of Methylated SEPT9 in Plasma Is a Reliable Screening Method for Both Left- and Right-Sided Colon Cancers
Tóth, Kinga ;
Sipos, Ferenc ;
Kalmár, Alexandra ;
Patai, Árpád V. ;
Wichmann, Barnabás ;
Stoehr, Robert ;
Golcher, Henriette ;
Schellerer, Vera ;
Tulassay, Zsolt ;
||(2012) PLoS ONE 7.9 (2012): 30.10.2012 <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0046000>
||Universität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / 2012
|Kurzfassung in Englisch:
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.
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.
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.