Journal Article

Detection of Methylated SEPT9 in Plasma Is a Reliable Screening Method for Both Left- and Right-Sided Colon Cancers

Molnár, Béla, Kalmár, Alexandra, Sipos, Ferenc, Schellerer, Vera, Wichmann, Barnabás, Patai, Árpád V., Golcher, Henriette, Tulassay, Zsolt, Stoehr, Robert, Tóth, Kinga

2012

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aged / Antigens / Binding proteins / Biomarkers / Bisulfite / Blood / Blood tests / Cancer / Carcinoembryonic antigen / Carcinoembryonic Antigen - metabolism / Case-Control Studies / Colon / Colon cancer / Colonic Neoplasms - blood / Colonic Neoplasms - diagnosis / Colonic Neoplasms - genetics / Colonoscopy / Colorectal cancer / Colorectal carcinoma / Deoxyribonucleic acid / Diagnosis / DNA / DNA Methylation / Endoscopy / Ethics / Family medical history / Feces / Female / Gene expression / Gene Expression Regulation, Neoplastic / Genetic aspects / Guaiac / Health aspects / Humans / Innovations / Internal medicine / Localization / Male / Medical screening / Medicine / Methods / Middle Aged / Molecular diagnostic techniques / Mortality / Occult Blood / Peripheral blood / Polymerase chain reaction / Reproducibility of Results / Sensitivity / Sensitivity and Specificity / Septin / Septins - blood / Septins - genetics / Septins - metabolism / Studies / Surgery