Biomarker Commons

Metagenomic biomarker discovery and explanation.

Genome Biol. 2011;12(6):R60

Authors: Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C

Abstract
This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

PMID: 21702898 [PubMed - indexed for MEDLINE]

Serum levels of soluble receptor for advanced glycation endproducts (sRAGE) are higher in ulcerative colitis and correlate with disease activity.

J Crohns Colitis. 2011 Oct;5(5):402-6

Authors: Yilmaz Y, Yonal O, Eren F, Atug O, Hamzaoglu HO

Abstract
UNLABELLED: Interaction of the receptor for advanced glycation endproducts (RAGE) with its ligands results in expression of inflammatory mediators, activation of NF-κB, and induction of oxidative stress, all of which have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Soluble receptor for advanced glycation endproducts (sRAGE) has recently emerged as a reliable biomarker of inflammation in numerous RAGE-mediated disorders.
OBJECTIVE: To assess sRAGE levels in adult patients with IBD.
METHOD: Serum was collected from adult patients with Crohn's disease (CD, 56 patients), ulcerative colitis (UC, 60 patients), and healthy controls (HC, 113 subjects). Levels of sRAGE were determined by enzyme-linked immunosorbent assay.
RESULTS: Serum sRAGE levels were elevated in IBD compared to HC and were higher in UC patients compared to CD and HC. Levels of sRAGE were significantly higher in the serum of UC patients with active disease compared to patients with inactive disease, but no association with the Montreal Classification was evident. Serum sRAGE was lower in CD patients with biological therapies.
CONCLUSIONS: These findings suggest that serum levels of sRAGE are altered in patients with intestinal inflammation and may reflect distinct immunoinflammatory pathogenesis of UC and CD.

PMID: 21939913 [PubMed - indexed for MEDLINE]

Candidate mucosal and surrogate biomarkers of inflammatory bowel disease in the era of new technology.

Scand J Gastroenterol. 2011 Dec;46(12):1407-17

Authors: Florholmen J, Fries W

Abstract
OBJECTIVE: There is increasing knowledge of the pathophysiology behind inflammatory bowel disease (IBD) although the exact mechanism is far from fully understood. In the era of new technology, over the last years molecular approaches have shed light on the inflammatory mechanisms and their metabolic end products. This opens for a molecular fingerprinting that can be used in the biomarker field of IBD. There is a great need of biomarkers for prediction of clinical outcome and prognostic biomarker for prediction of therapeutic effects in IBD. Although the biomarker concept is old, so far very few really useful biomarkers exist in IBD.
MATERIAL AND METHODS: Here, we review the predictive and prognostic biomarkers in IBD in the era of new technologies with emphasis on the potential of molecular fingerprinting.
RESULTS: Very few candidate biomarkers have been documented. The most promising candidate predictor is tumor necrosis factor-α, but there is a lack of validation.
CONCLUSION: So far, there are few biomarkers documented in IBD, but we are at the start of a new scientific field that will be of great value for the handling of the disease.

PMID: 22040230 [PubMed - indexed for MEDLINE]

Chitinase 3-like-1 expression in colonic epithelial cells as a potentially novel marker for colitis-associated neoplasia.

Am J Pathol. 2011 Sep;179(3):1494-503

Authors: Chen CC, Pekow J, Llado V, Kanneganti M, Lau CW, Mizoguchi A, Mino-Kenudson M, Bissonnette M, Mizoguchi E

Abstract
Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by IHC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-κB signaling pathway and enhanced the secretion of IL-8 and TNF-α in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD.

PMID: 21763261 [PubMed - indexed for MEDLINE]