Biomarkers of Inflammatory Bowel Disease: From Classical Laboratory Tools to Personalized Medicine

Abstract:Diagnostics of inflammatory bowel diseases (IBDs) currently relies on a combination of biological and morphological tests. The current method of diagnostic remains a critical challenge for physicians in part due to their invasiveness and also for their limitations in term of diagnosis, prognosis, disease activity and severity assessment, and therapeutic outcomes. Laboratory biomarkers can be used in the diagnosis and management of IBD, but none of them has been proven to be ideal. Increasing efforts are being made to discover new biomarkers that can discriminate between the types of IBD, predict future responses to treatment, and aid in differential diagnosis, treatment planning, and prognosis prediction. This review addresses the potential for current biomarkers and the emergence of the concept of biomarker signatures in IBD diagnostic and personalized medicine.

[1]  A. Kapsoritakis,et al.  Neutrophil gelatinase-associated lipocalin (NGAL) in inflammatory bowel disease: association with pathophysiology of inflammation, established markers, and disease activity , 2012, Journal of Gastroenterology.

[2]  P. Rutgeerts,et al.  Laboratory markers in IBD: useful, magic, or unnecessary toys? , 2006, Gut.

[3]  I. Dale,et al.  A radioimmunoassay for a granulocyte protein as a marker in studies on the turnover of such cells. , 1980, Bulletin europeen de physiopathologie respiratoire.

[4]  P. Rutgeerts,et al.  The value of serologic markers in indeterminate colitis: a prospective follow-up study. , 2003, Gastroenterology.

[5]  A. Vaiopoulou,et al.  Serum protein profile of Crohn's disease treated with infliximab. , 2013, Journal of Crohn's & colitis.

[6]  A. Røseth,et al.  Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. , 1992, Scandinavian journal of gastroenterology.

[7]  A. Darzi,et al.  Diagnostic Precision of Anti-Saccharomyces cerevisiae Antibodies and Perinuclear Antineutrophil Cytoplasmic Antibodies in Inflammatory Bowel Disease , 2006, The American Journal of Gastroenterology.

[8]  P. Hoff,et al.  Serum protein profiling reveals baseline and pharmacodynamic biomarker signatures associated with clinical outcome in mCRC patients treated with chemotherapy ± cediranib , 2014, British Journal of Cancer.

[9]  Igor M. Dozmorov,et al.  Identification of Unique MicroRNA Signature Associated with Lupus Nephritis , 2010, PloS one.

[10]  S. Kugathasan,et al.  Fecal calprotectin is useful in predicting disease relapse in pediatric inflammatory bowel disease , 2008, Inflammatory bowel diseases.

[11]  Mei Zhao,et al.  Identification of a Circulating MicroRNA Signature for Colorectal Cancer Detection , 2014, PloS one.

[12]  J. Mate,et al.  Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse , 2009, Inflammatory bowel diseases.

[13]  Keith W. Jones,et al.  Genome-Wide Maps of Circulating miRNA Biomarkers for Ulcerative Colitis , 2012, PloS one.

[14]  A. Røseth,et al.  Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease , 2004, Scandinavian journal of gastroenterology.

[15]  A. Day,et al.  S100A12: A noninvasive marker of inflammation in inflammatory bowel disease , 2013, Journal of digestive diseases.

[16]  Philippe Seksik,et al.  Epidemiology and natural history of inflammatory bowel diseases. , 2011, Gastroenterology.

[17]  P. Malfertheiner,et al.  Feasibility of Fecal MicroRNAs as Novel Biomarkers for Pancreatic Cancer , 2012, PloS one.

[18]  S. Brant,et al.  MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. , 2008, Gastroenterology.

[19]  S. Brant,et al.  Peripheral blood MicroRNAs distinguish active ulcerative colitis and Crohn's disease , 2011, Inflammatory bowel diseases.

[20]  I. Leodolter [Crohn's disease]. , 1967, Wiener Zeitschrift fur innere Medizin und ihre Grenzgebiete.

[21]  P. Geurts,et al.  Proteomics for prediction and characterization of response to infliximab in Crohn's disease: a pilot study. , 2008, Clinical biochemistry.

[22]  A. Chinnaiyan,et al.  MicroRNA expression patterns in indeterminate inflammatory bowel disease , 2013, Modern Pathology.

[23]  M. Leonard,et al.  Circulating MicroRNA Is a Biomarker of Pediatric Crohn Disease , 2011, Journal of pediatric gastroenterology and nutrition.

[24]  W. Sjursen,et al.  Identification of serum microRNA profiles in colon cancer , 2013, British Journal of Cancer.

[25]  M. Camilleri,et al.  Fecal Lactoferrin Is a Sensitive and Specific Marker in Identifying Intestinal Inflammation , 2003, American Journal of Gastroenterology.

[26]  F. Marabita,et al.  Identification of serum and tissue micro‐RNA expression profiles in different stages of inflammatory bowel disease , 2013, Clinical and experimental immunology.

[27]  E. Chan,et al.  Global fecal microRNA profiling in the identification of biomarkers for colorectal cancer screening among Asians. , 2014, Oncology reports.

[28]  J. Jahnsen,et al.  Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein. , 1997, Digestion.

[29]  M. Neurath,et al.  Mouse models of inflammatory bowel disease. , 2007, Advanced drug delivery reviews.

[30]  C. Boland,et al.  Fecal MicroRNAs as Novel Biomarkers for Colon Cancer Screening , 2010, Cancer Epidemiology, Biomarkers & Prevention.

[31]  D. Foell,et al.  Neutrophil-derived S100A12 is profoundly upregulated in the early stage of acute Kawasaki disease. , 2004, The American journal of cardiology.

[32]  S. Ng,et al.  Geographical variability and environmental risk factors in inflammatory bowel disease , 2013, Gut.

[33]  A. Zinsmeister,et al.  Correlation of C‐Reactive Protein With Clinical, Endoscopic, Histologic, and Radiographic Activity in Inflammatory Bowel Disease , 2005, Inflammatory bowel diseases.

[34]  O. Nielsen,et al.  miR-20b, miR-98, miR-125b-1*, and let-7e* as new potential diagnostic biomarkers in ulcerative colitis. , 2013, World journal of gastroenterology.

[35]  Zhongmin Liu,et al.  C-Reactive Protein in Human Atherogenesis: Facts and Fiction , 2014, Mediators of inflammation.

[36]  Carsten Peterson,et al.  Detection of pancreatic cancer using antibody microarray‐based serum protein profiling , 2008, Proteomics.

[37]  Y. Naito,et al.  Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis , 2010, Journal of gastroenterology and hepatology.

[38]  David Westhead,et al.  Prediction of clinical outcome in glioblastoma using a biologically relevant nine‐microRNA signature , 2015, Molecular oncology.

[39]  M. Lentze,et al.  Fecal Lactoferrin: A New Parameter to Monitor Infliximab Therapy , 2004, Digestive Diseases and Sciences.

[40]  P. Bakke,et al.  Neutrophil gelatinase-associated lipocalin: a biomarker in COPD. , 2010, Chest.

[41]  M. Färkkilä,et al.  Fecal calprotectin, lactoferrin, and endoscopic disease activity in monitoring anti‐TNF‐alpha therapy for Crohn's disease , 2008, Inflammatory bowel diseases.

[42]  M. Färkkilä,et al.  Faecal calprotectin and lactoferrin are reliable surrogate markers of endoscopic response during Crohn's disease treatment , 2010, Scandinavian journal of gastroenterology.

[43]  R. Stock,et al.  C‐reactive protein is significantly associated with prostate‐specific antigen and metastatic disease in prostate cancer , 2005, BJU international.

[44]  Heng-jun Gao,et al.  Aberrant expression of microRNAs in serum may identify individuals with pancreatic cancer. , 2014, International journal of clinical and experimental medicine.

[45]  M. Bottai,et al.  Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease , 2005, Gut.

[46]  C. Geczy,et al.  S100 Calgranulins in inflammatory arthritis , 2010, Immunology and cell biology.

[47]  L. Du,et al.  Serum microRNA expression signatures identified from genome‐wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer , 2015, International journal of cancer.

[48]  G. Heinze,et al.  Serum C-reactive protein in the differential diagnosis of ovarian masses. , 2009, European journal of obstetrics, gynecology, and reproductive biology.

[49]  Thomas Francis,et al.  SEROLOGICAL REACTIONS IN PNEUMONIA WITH A NON-PROTEIN SOMATIC FRACTION OF PNEUMOCOCCUS , 1930, The Journal of experimental medicine.

[50]  A. Schetter,et al.  Identification of a metastasis-specific MicroRNA signature in human colorectal cancer. , 2015, Journal of the National Cancer Institute.

[51]  R. Donato,et al.  Intracellular and extracellular roles of S100 proteins , 2003, Microscopy research and technique.

[52]  Linda S. Lee,et al.  A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer. , 2014, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[53]  A. Young,et al.  Fecal Lipocalin 2, a Sensitive and Broadly Dynamic Non-Invasive Biomarker for Intestinal Inflammation , 2012, PloS one.

[54]  K. Pienta,et al.  Circulating microRNA Profiling Identifies a Subset of Metastatic Prostate Cancer Patients with Evidence of Cancer-Associated Hypoxia , 2013, PloS one.

[55]  Bo Xiao,et al.  Longitudinal study of circulating protein biomarkers in inflammatory bowel disease. , 2015, Journal of proteomics.

[56]  D E McMillan,et al.  Increased levels of acute-phase serum proteins in diabetes. , 1989, Metabolism: clinical and experimental.

[57]  S. Targan,et al.  Diagnostic accuracy of serological assays in pediatric inflammatory bowel disease. , 1998, Gastroenterology.

[58]  I. Bjarnason,et al.  Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. , 2000, Gastroenterology.

[59]  M. Bertagnolli,et al.  Prognostic and Predictive Blood-Based Biomarkers in Patients with Advanced Pancreatic Cancer: Results from CALGB80303 (Alliance) , 2013, Clinical Cancer Research.

[60]  P. Geurts,et al.  Biomarker discovery for inflammatory bowel disease, using proteomic serum profiling. , 2007, Biochemical pharmacology.

[61]  M. Lewandowska,et al.  Prognostic and Predictive Biomarkers: Tools in Personalized Oncology , 2014, Molecular Diagnosis & Therapy.

[62]  M. Casale,et al.  Serum protein profiling in patients with inflammatory bowel diseases using selective solid-phase bulk extraction, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemometric data analysis. , 2007, Rapid communications in mass spectrometry : RCM.

[63]  A. Petrie,et al.  Immunological studies in inflammatory bowel disease. , 1977, Ciba Foundation symposium.

[64]  A. Day,et al.  Fecal S100A12: A novel noninvasive marker in children with Crohn's disease , 2006, Inflammatory bowel diseases.

[65]  Stephen A. Williams,et al.  Validation of a blood protein signature for non-small cell lung cancer , 2014, Clinical Proteomics.

[66]  M. Gazouli,et al.  Circulating MicroRNA in inflammatory bowel disease. , 2012, Journal of Crohn's & colitis.

[67]  A. Griffiths,et al.  Faecal calprotectin, lactoferrin, M2-pyruvate kinase and S100A12 in severe ulcerative colitis: a prospective multicentre comparison of predicting outcomes and monitoring response , 2010, Gut.

[68]  J. Schölmerich,et al.  A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. , 1990, Immunobiology.

[69]  M. Bissonnette,et al.  miR‐143 and miR‐145 are downregulated in ulcerative colitis: Putative regulators of inflammation and protooncogenes , 2012, Inflammatory bowel diseases.

[70]  C. Borrebaeck,et al.  Identification of serum biomarker signatures associated with pancreatic cancer. , 2012, Cancer research.

[71]  S. Fais,et al.  The clinical significance of serum C reactive protein levels in Crohn's disease. Results of a prospective longitudinal study. , 1988, Journal of clinical gastroenterology.

[72]  I. Hirata,et al.  Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. , 1996, The American journal of gastroenterology.

[73]  P. Tan,et al.  Identification of Circulating MicroRNA Signatures for Breast Cancer Detection , 2013, Clinical Cancer Research.

[74]  Mark B Pepys,et al.  C-reactive protein: a critical update. , 2003, The Journal of clinical investigation.

[75]  S. Dahan,et al.  MicroRNA-7 Modulates CD98 Expression during Intestinal Epithelial Cell Differentiation* , 2009, The Journal of Biological Chemistry.

[76]  B. Flourié,et al.  Accuracies of Serum and Fecal S100 Proteins (Calprotectin and Calgranulin C) to Predict the Response to TNF Antagonists in Patients with Crohn's Disease , 2015, Inflammatory bowel diseases.

[77]  P. Lakatos,et al.  The burden of inflammatory bowel disease in Europe. , 2013, Journal of Crohn's & colitis.

[78]  M. Färkkilä,et al.  Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn’s disease and histological findings , 2008, Alimentary pharmacology & therapeutics.

[79]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[80]  Y Raab,et al.  Human neutrophil lipocalin is a unique marker of neutrophil inflammation in ulcerative colitis and proctitis , 2002, Gut.

[81]  J. Małyszko,et al.  Serum Neutrophil Gelatinase-Associated Lipocalin as a Marker of Renal Function in Non-Diabetic Patients with Stage 2–4 Chronic Kidney Disease , 2008, Renal failure.

[82]  Stefano Volinia,et al.  MicroRNA Profiles Discriminate among Colon Cancer Metastasis , 2014, PloS one.

[83]  G. Shurin,et al.  C-reactive protein and lung diseases. , 2014, The international journal of biochemistry & cell biology.

[84]  D. Lawlor,et al.  A systematic review of the association between circulating concentrations of C reactive protein and cancer , 2007, Journal of Epidemiology and Community Health.

[85]  Kazutaka Saito,et al.  C-reactive protein as a biomarker for urological cancers , 2011, Nature Reviews Urology.

[86]  L. Kjeldsen,et al.  Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse. , 2000, Biochimica et biophysica acta.

[87]  P. Renzulli,et al.  Ulcerative colitis: Correlation of the Rachmilewitz endoscopic activity index with fecal calprotectin, clinical activity, C‐reactive protein, and blood leukocytes , 2009, Inflammatory bowel diseases.

[88]  Subrata Ghosh,et al.  Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. , 2012, Gastroenterology.

[89]  M. Färkkilä,et al.  Crohn's disease activity assessed by fecal calprotectin and lactoferrin: Correlation with Crohn's disease activity index and endoscopic findings , 2008, Inflammatory bowel diseases.

[90]  M. Neurath,et al.  RAGE Mediates a Novel Proinflammatory Axis A Central Cell Surface Receptor for S100/Calgranulin Polypeptides , 1999, Cell.

[91]  R. Søkilde,et al.  Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). , 2011, Blood.

[92]  E. Ogier-Denis,et al.  Identification of Restricted Subsets of Mature microRNA Abnormally Expressed in Inactive Colonic Mucosa of Patients with Inflammatory Bowel Disease , 2010, PloS one.

[93]  G. Porro,et al.  Serum protein profiling of early and advanced stage Crohn's disease , 2014 .

[94]  P. Rutgeerts,et al.  Diagnostic approach to IBD. , 2000, Hepato-gastroenterology.

[95]  Z. Yamagata,et al.  Neutrophil gelatinase-associated lipocalin levels associated with cardiovascular disease in chronic kidney disease patients , 2014, Clinical and Experimental Nephrology.

[96]  S. Brant,et al.  Identification of microRNAs associated with ileal and colonic Crohn's disease† , 2010, Inflammatory bowel diseases.