Detection of Colorectal Disease by Stool Defensin Assay: An Exploratory Study

Hongzhi Zou, Jonathan J. Harrington, Aravind Sugumar, Kristie K. Klatt, Thomas Christopher Smyrk, David A. Ahlquist

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)865-868
Number of pages4
JournalClinical Gastroenterology and Hepatology
Volume5
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Defensins
Colorectal Neoplasms
alpha-Defensins
Gastrointestinal Neoplasms
Leukocytes
Adenoma
Lactoferrin
Cell Line
Epithelium
Neoplasms
Messenger RNA
Proteins
Colonic Neoplasms
Neutrophils

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Zou, H., Harrington, J. J., Sugumar, A., Klatt, K. K., Smyrk, T. C., & Ahlquist, D. A. (2007). Detection of Colorectal Disease by Stool Defensin Assay: An Exploratory Study. Clinical Gastroenterology and Hepatology, 5(7), 865-868. https://doi.org/10.1016/j.cgh.2007.03.013

Detection of Colorectal Disease by Stool Defensin Assay : An Exploratory Study. / Zou, Hongzhi; Harrington, Jonathan J.; Sugumar, Aravind; Klatt, Kristie K.; Smyrk, Thomas Christopher; Ahlquist, David A.

In: Clinical Gastroenterology and Hepatology, Vol. 5, No. 7, 07.2007, p. 865-868.

Research output: Contribution to journalArticle

Zou, H, Harrington, JJ, Sugumar, A, Klatt, KK, Smyrk, TC & Ahlquist, DA 2007, 'Detection of Colorectal Disease by Stool Defensin Assay: An Exploratory Study', Clinical Gastroenterology and Hepatology, vol. 5, no. 7, pp. 865-868. https://doi.org/10.1016/j.cgh.2007.03.013
Zou, Hongzhi ; Harrington, Jonathan J. ; Sugumar, Aravind ; Klatt, Kristie K. ; Smyrk, Thomas Christopher ; Ahlquist, David A. / Detection of Colorectal Disease by Stool Defensin Assay : An Exploratory Study. In: Clinical Gastroenterology and Hepatology. 2007 ; Vol. 5, No. 7. pp. 865-868.
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abstract = "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.",
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AU - Zou, Hongzhi

AU - Harrington, Jonathan J.

AU - Sugumar, Aravind

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AU - Smyrk, Thomas Christopher

AU - Ahlquist, David A.

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N2 - 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.

AB - 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.

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