Abstract
BackgroundMethylated 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 FindingsPlasma 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/SignificanceThe 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.
Highlights
Colorectal cancer (CRC) is the third most common malignancy worldwide, with more than 1.2 million new cases and 808,700 deaths in the year 2008 [1]
2 no evidence of disease (NED) and 1 colorectal cancer (CRC) samples yielded both Septin 9 positive and negative results; they were excluded from the study
The samples from two NED subjects and one CRC patient yielded both Septin 9 positive and negative results; they were excluded from the study
Summary
Colorectal cancer (CRC) is the third most common malignancy worldwide, with more than 1.2 million new cases and 808,700 deaths in the year 2008 [1]. In a multicenter randomized controlled study, sigmoidoscopy reduced CRC incidence by 23% and mortality by 31% and reduced the incidence of distal colon cancer (rectum and sigmoid colon) by 50% [6] The limitations of this diagnostic method are the need for bowel preparation, the relatively high cost, and the inability to detect proximal colonic lesions. Case-control studies have shown reduction of CRC incidence by 53–72% and reduction of mortality by 31% [7,8] It has the highest specificity, there are several limitations, such as the need for bowel preparation, expertise, cost, invasiveness, availability, low adherence rate, and occasional serious complications. We compared SEPT9 to a routine fecal-based screening method (gFOBT) and a blood-based tumor marker (CEA) since no such study had yet been performed
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