Assessment of the validity of a multigene analysis in the diagnostics of inflammatory bowel disease

J T Bjerrum; Caroline Nyberg; J Olsen; O H Nielsen

doi:10.1111/joim.12160

Assessment of the validity of a multigene analysis in the diagnostics of inflammatory bowel disease

J T Bjerrum, Caroline Nyberg, J Olsen, O H Nielsen

13 Citations (Scopus)

Abstract

OBJECTIVES: The findings of a previous multigene study indicated that the expression of a panel of seven specific genes had strong differential power regarding inflammatory bowel disease (IBD) versus non-IBD, as well as ulcerative colitis (UC) versus Crohn's disease (CD). This prospective confirmatory study based on an independent patient cohort from a national Danish IBD centre was conducted in an attempt to verify these earlier observations.

DESIGN, SETTING AND PARTICIPANTS: A total of 119 patients were included in the study (CD, UC and controls). Three mucosal biopsies were retrieved from the left side of the colon of each patient. RNA was extracted, and RT-PCR was performed to retain expression profiles from the seven selected genes. Expression data from the training set (18 CD, 20 UC and 20 controls) were used to build a classification model, using quadratic discriminant analysis, and data from the test set (20 CD, 21 UC and 20 controls) were used to test the validity of the model.

RESULTS: The present investigation did not confirm the previous observation that a panel of seven specific genes is able to distinguish between patients with CD and UC, whereas the discriminative power for IBD versus control subjects was substantiated.

CONCLUSION: Our results fail to demonstrate that the previously identified seven-gene classification model is able to discriminate between CD and UC but suggest that the gene panel merely discriminates between inflamed and noninflamed colonic tissue. Thus, a reliable and simple diagnostic tool is still warranted for optimal diagnosis and treatment of patients with IBD, especially the subgroup with unclassified disease.

Original language	English
Journal	Journal of Internal Medicine
Volume	275
Issue number	5
Pages (from-to)	484-93
Number of pages	10
ISSN	0954-6820
DOIs	https://doi.org/10.1111/joim.12160
Publication status	Published - May 2014

Keywords

Adult
Amidohydrolases
Amino Acid Transport Systems, Neutral
Anion Transport Proteins
Area Under Curve
Chemokine CXCL1
Colitis, Ulcerative
Crohn Disease
Female
GPI-Linked Proteins
Gene Expression
Genetic Markers
Humans
Lectins, C-Type
Male
Matrix Metalloproteinase 7
Membrane Proteins
Prospective Studies
Real-Time Polymerase Chain Reaction

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title = "Assessment of the validity of a multigene analysis in the diagnostics of inflammatory bowel disease",

abstract = "OBJECTIVES: The findings of a previous multigene study indicated that the expression of a panel of seven specific genes had strong differential power regarding inflammatory bowel disease (IBD) versus non-IBD, as well as ulcerative colitis (UC) versus Crohn's disease (CD). This prospective confirmatory study based on an independent patient cohort from a national Danish IBD centre was conducted in an attempt to verify these earlier observations.DESIGN, SETTING AND PARTICIPANTS: A total of 119 patients were included in the study (CD, UC and controls). Three mucosal biopsies were retrieved from the left side of the colon of each patient. RNA was extracted, and RT-PCR was performed to retain expression profiles from the seven selected genes. Expression data from the training set (18 CD, 20 UC and 20 controls) were used to build a classification model, using quadratic discriminant analysis, and data from the test set (20 CD, 21 UC and 20 controls) were used to test the validity of the model.RESULTS: The present investigation did not confirm the previous observation that a panel of seven specific genes is able to distinguish between patients with CD and UC, whereas the discriminative power for IBD versus control subjects was substantiated.CONCLUSION: Our results fail to demonstrate that the previously identified seven-gene classification model is able to discriminate between CD and UC but suggest that the gene panel merely discriminates between inflamed and noninflamed colonic tissue. Thus, a reliable and simple diagnostic tool is still warranted for optimal diagnosis and treatment of patients with IBD, especially the subgroup with unclassified disease.",

keywords = "Adult, Amidohydrolases, Amino Acid Transport Systems, Neutral, Anion Transport Proteins, Area Under Curve, Chemokine CXCL1, Colitis, Ulcerative, Crohn Disease, Female, GPI-Linked Proteins, Gene Expression, Genetic Markers, Humans, Lectins, C-Type, Male, Matrix Metalloproteinase 7, Membrane Proteins, Prospective Studies, Real-Time Polymerase Chain Reaction",

author = "Bjerrum, {J T} and Caroline Nyberg and J Olsen and Nielsen, {O H}",

note = "{\textcopyright} 2013 The Association for the Publication of the Journal of Internal Medicine.",

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month = may,

doi = "10.1111/joim.12160",

language = "English",

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T1 - Assessment of the validity of a multigene analysis in the diagnostics of inflammatory bowel disease

AU - Bjerrum, J T

AU - Nyberg, Caroline

AU - Olsen, J

AU - Nielsen, O H

PY - 2014/5

Y1 - 2014/5

N2 - OBJECTIVES: The findings of a previous multigene study indicated that the expression of a panel of seven specific genes had strong differential power regarding inflammatory bowel disease (IBD) versus non-IBD, as well as ulcerative colitis (UC) versus Crohn's disease (CD). This prospective confirmatory study based on an independent patient cohort from a national Danish IBD centre was conducted in an attempt to verify these earlier observations.DESIGN, SETTING AND PARTICIPANTS: A total of 119 patients were included in the study (CD, UC and controls). Three mucosal biopsies were retrieved from the left side of the colon of each patient. RNA was extracted, and RT-PCR was performed to retain expression profiles from the seven selected genes. Expression data from the training set (18 CD, 20 UC and 20 controls) were used to build a classification model, using quadratic discriminant analysis, and data from the test set (20 CD, 21 UC and 20 controls) were used to test the validity of the model.RESULTS: The present investigation did not confirm the previous observation that a panel of seven specific genes is able to distinguish between patients with CD and UC, whereas the discriminative power for IBD versus control subjects was substantiated.CONCLUSION: Our results fail to demonstrate that the previously identified seven-gene classification model is able to discriminate between CD and UC but suggest that the gene panel merely discriminates between inflamed and noninflamed colonic tissue. Thus, a reliable and simple diagnostic tool is still warranted for optimal diagnosis and treatment of patients with IBD, especially the subgroup with unclassified disease.

AB - OBJECTIVES: The findings of a previous multigene study indicated that the expression of a panel of seven specific genes had strong differential power regarding inflammatory bowel disease (IBD) versus non-IBD, as well as ulcerative colitis (UC) versus Crohn's disease (CD). This prospective confirmatory study based on an independent patient cohort from a national Danish IBD centre was conducted in an attempt to verify these earlier observations.DESIGN, SETTING AND PARTICIPANTS: A total of 119 patients were included in the study (CD, UC and controls). Three mucosal biopsies were retrieved from the left side of the colon of each patient. RNA was extracted, and RT-PCR was performed to retain expression profiles from the seven selected genes. Expression data from the training set (18 CD, 20 UC and 20 controls) were used to build a classification model, using quadratic discriminant analysis, and data from the test set (20 CD, 21 UC and 20 controls) were used to test the validity of the model.RESULTS: The present investigation did not confirm the previous observation that a panel of seven specific genes is able to distinguish between patients with CD and UC, whereas the discriminative power for IBD versus control subjects was substantiated.CONCLUSION: Our results fail to demonstrate that the previously identified seven-gene classification model is able to discriminate between CD and UC but suggest that the gene panel merely discriminates between inflamed and noninflamed colonic tissue. Thus, a reliable and simple diagnostic tool is still warranted for optimal diagnosis and treatment of patients with IBD, especially the subgroup with unclassified disease.

KW - Adult

KW - Amidohydrolases

KW - Amino Acid Transport Systems, Neutral

KW - Anion Transport Proteins

KW - Area Under Curve

KW - Chemokine CXCL1

KW - Colitis, Ulcerative

KW - Crohn Disease

KW - Female

KW - GPI-Linked Proteins

KW - Gene Expression

KW - Genetic Markers

KW - Humans

KW - Lectins, C-Type

KW - Male

KW - Matrix Metalloproteinase 7

KW - Membrane Proteins

KW - Prospective Studies

KW - Real-Time Polymerase Chain Reaction

U2 - 10.1111/joim.12160

DO - 10.1111/joim.12160

M3 - Journal article

C2 - 24206446

SN - 0954-6820

VL - 275

SP - 484

EP - 493

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

IS - 5

ER -

Assessment of the validity of a multigene analysis in the diagnostics of inflammatory bowel disease

Abstract

Keywords

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