BACKGROUND & AIMS: Alpha-defensins 1-3 (human neutrophil peptides [HNP]1-3), reported to be elevated in tumor tissue and serum of patients with colorectal cancer (CRC), have not been studied in stool. We evaluated the neoplasm specificity of HPN1-3 and their discriminant value as stool markers for CRC. METHODS: Protein and mRNA expression of HPN1-3 were assayed in CRC cell lines, microdissected CRC and normal epithelium, and white blood cells. HNP1-3 proteins in stools were quantified in blinded fashion from 30 normal subjects, 20 patients with CRC, 10 with a large colorectal adenoma, 10 with upper gastrointestinal cancer, and 10 with IBD. Stool lactoferrin was also quantified. RESULTS: HPN1-3 proteins were not detected in CRC cell lines but were high (>4000 ng/mL) in white blood cells. mRNA levels of HPN1-3 were comparably low in CRC cell lines, microdissected CRC, and normal colon epithelium, but they were >1000-fold and >30,000-fold higher in white blood cells and neutrophils, respectively. Mean stool HPN1-3 levels were 17 ng/mL with normals, 125 ng/mL with CRC, 62 ng/mL with adenoma, 63 ng/mL with upper gastrointestinal cancer, and 231 ng/mL with IBD (P < .01 for each patient group vs normals). HPN1-3 levels in IBD were higher than in CRC (P = .04). At 90% specificity, sensitivity of stool defensins was 35% for CRC, 40% for adenoma, 40% for upper gastrointestinal cancers, and 80% for IBD. Stool defensins and lactoferrin levels correlated (R2 = 0.70, P < .001). CONCLUSIONS: Alpha-defensins 1-3 levels are nonspecifically elevated in stools from patients with colorectal neoplasia and likely originate from white blood cells. Alpha-defensins 1-3 in stool might serve as markers of inflammatory bowel conditions.
BACKGROUND & AIMS: Alpha-defensins 1-3 (human neutrophil peptides [HNP]1-3), reported to be elevated in tumor tissue and serum of patients with colorectal cancer (CRC), have not been studied in stool. We evaluated the neoplasm specificity of HPN1-3 and their discriminant value as stool markers for CRC. METHODS: Protein and mRNA expression of HPN1-3 were assayed in CRC cell lines, microdissected CRC and normal epithelium, and white blood cells. HNP1-3 proteins in stools were quantified in blinded fashion from 30 normal subjects, 20 patients with CRC, 10 with a large colorectal adenoma, 10 with upper gastrointestinal cancer, and 10 with IBD. Stool lactoferrin was also quantified. RESULTS:HPN1-3 proteins were not detected in CRC cell lines but were high (>4000 ng/mL) in white blood cells. mRNA levels of HPN1-3 were comparably low in CRC cell lines, microdissected CRC, and normal colon epithelium, but they were >1000-fold and >30,000-fold higher in white blood cells and neutrophils, respectively. Mean stool HPN1-3 levels were 17 ng/mL with normals, 125 ng/mL with CRC, 62 ng/mL with adenoma, 63 ng/mL with upper gastrointestinal cancer, and 231 ng/mL with IBD (P < .01 for each patient group vs normals). HPN1-3 levels in IBD were higher than in CRC (P = .04). At 90% specificity, sensitivity of stool defensins was 35% for CRC, 40% for adenoma, 40% for upper gastrointestinal cancers, and 80% for IBD. Stool defensins and lactoferrin levels correlated (R2 = 0.70, P < .001). CONCLUSIONS: Alpha-defensins 1-3 levels are nonspecifically elevated in stools from patients with colorectal neoplasia and likely originate from white blood cells. Alpha-defensins 1-3 in stool might serve as markers of inflammatory bowel conditions.
Authors: John B Kisiel; Megan M Garrity-Park; William R Taylor; Thomas C Smyrk; David A Ahlquist Journal: Inflamm Bowel Dis Date: 2013-09 Impact factor: 5.325
Authors: Vojtech Adam; Ondrej Zitka; Petr Dolezal; Ladislav Zeman; Ales Horna; Jaromir Hubalek; Jan Sileny; Sona Krizkova; Libuse Trnkova; Rene Kizek Journal: Sensors (Basel) Date: 2008-01-24 Impact factor: 3.576
Authors: Mariya Y Radeva; Franziska Jahns; Anne Wilhelm; Michael Glei; Utz Settmacher; Karl Otto Greulich; Henning Mothes Journal: BMC Cancer Date: 2010-10-27 Impact factor: 4.430