Author(s): Tth K, Sipos F, Kalmr A, Patai AV, Wichmann B,
Abstract Share this page
Abstract 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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.
This article was published in PLoS One
and referenced in Journal of Molecular Biomarkers & Diagnosis