It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

Purpose: Fecal occult blood testing is recommended as first-line screening to detect colorectal cancer (CRC). We evaluated markers and marker combinations in serum as an alternative to improve the detection of CRC.Experimental Design: Using penalized logistic regression, 6 markers were selected for evaluation in 1,027 samples (301 CRC patients, 143 patients with adenoma, 266 controls, 141 disease controls, and 176 patients with other cancer). The diagnostic performance of each marker and of marker combinations was assessed.Results: To detect CRC from serum samples, we tested 22 biomarkers. Six markers were selected for a marker combination, including the known tumor markers CEA (carcinoembryonic antigen) and CYFRA 21-1 as well as novel markers or markers that are less routinely used for the detection of CRC: ferritin, osteopontin (OPN), anti-p53, and seprase. CEA showed the best sensitivity at 95% specificity with 43.9%, followed by seprase (42.4%), CYFRA 21-1 (35.5%), OPN (30.2%), ferritin (23.9%), and anti-p53 (20.0%). A combination of these markers gave 69.6% sensitivity at 95% specificity and 58.7% at 98% specificity. Focusing on International Union against Cancer (UICC) stages 0-III reduced the sensitivity slightly to 68.0% and 53.3%, respectively. In a subcollective, with matched stool samples (75 CRC cases and 234 controls), the sensitivity of the marker combination was comparable with fecal immunochemical testing (FIT) with 82.4% and 68.9% versus 81.8% and 72.7% at 95% and 98% specificity, respectively.Conclusions: The performance of the serum marker combination is comparable with FIT. This provides a novel tool for CRC screening to trigger a follow-up colonoscopy for a final diagnosis. Clin Cancer Res; 16(24); 6111-21. Ó2010 AACR.The early detection of colorectal cancer (CRC) significantly improves the prognosis of patients and is a key factor to reduce the mortality from CRC (1). Recently, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology have issued joint guidelines for CRC screening to include well-known procedures as guaiac-based fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT), colonoscopy, sigmoidoscopy, and double-contrast barium enema, but also 2 more recent methods, computer tomography colonography and fecal DNA testing (2). The guidelines of the U.S. Preventive Services Task Force have also been updated but do not include the latter 2 methods (3).Serum-based, minimally invasive markers would be highly attractive for CRC screening as they could easily be integrated in any health checkup without the need of additional stool sampling. Although numerous biomarkers are under evaluation for the detection of CRC from serum, none of them has sufficient sensitivity and specificity to be considered in the current guidelines (4). Carcinoembryonic antigen (CEA) and carbohydrate antigens, for example, CA19-9 have been assessed more intensely but with varying results depending on the study design and the s...

The purpose of this study was to identify and validate novel serological protein biomarkers of human colorectal cancer (CRC).The PSME3-containing spot on tumor gels showed no visible difference to the corresponding spot on matched control gels. MS analysis revealed the presence of two proteins, PSME3 and annexin 4 (ANXA4) in one and the same spot on tumor gels, whereas the matched spot contained only one protein, ANXA4, on control gels. Therefore, dysregulation of PSME3 was masked by ANXA4 and could only be recognized by MS-based analysis but not by image analysis. To validate this finding, antibody to PSME3 was developed, and up-regulation in CRC was confirmed by Western blot analysis and immunohistochemistry. Finally by developing a highly sensitive immunoassay, PSME3 could be detected in human sera and was significantly elevated in CRC patients compared with healthy donors and patients with benign bowel disease. We propose that PSME3 be considered a novel serum tumor marker for CRC that may have significance in the detection and in the management of patients with this disease. Further studies are needed to fully assess the potential clinical value of this marker candidate.

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