Biomarker Discovery: Study Design and Execution - Proteomic and Metabolomic Approaches to Biomarker Discovery - page 2

ABBREVIATIONS

are used to examine the biological behavior of
a disease and predict the clinical outcome. The
biomarker should be disease speci

c and not
due to environmental conditions or biological
perturbations. To be clinically acceptable, a diag-
nostic biomarker should possess a sensitivity
and speci

LC liquid chromatography

HPLC

high performance LC

UPLC ultra-high-pressure LC

CE capillary electrophoresis

city as close to 100% as possible and
be measured within a noninvasive (urine) or
semi-invasive (blood) collected specimen. In
addition, the test should be accurate, econom-
ical, easy to perform, and reproducible by
different technicians across different laborato-
ries. A description of an ideal description of
diagnostic methods is provided in Figure 1 .
Although some biomarkers have been approved
by the Food and Drug Administration (FDA) as
qualitative tests for monitoring speci

GC gas chromatography

MS mass spectrometry

SDS-PAGE

sodium dodecyl sulfate-
polyacryl gel electrophoresis

INTRODUCTION

Diseases result in speci c changes in the

molecular pro fluids and tissue.

These changes can be detected by analyzing the
genetic, proteomic, or metabolomic composition
of samples. Proteomic and metabolomic analysis
provides the opportunity to detect diseases as
they occur; genetic analyses identify individuals
with predispositions to certain diseases and aid
in the determination of long-term risk. Therefore,
direct measurement of genes, proteins, and
metabolites is essential for the understanding
of biological processes in disease and normal
states. 1 Molecules produced by the body

les of biological

c cancers
(e.g., nuclear matrix protein-22 for bladder
cancer), the majority of discovered potential
biomarkers (proteins or metabolites) are not
sensitive and/or speci

c enough to be used for

population screening.

DEFINITIONS

s meta-
bolic processes may distinguish between two
different sample sets obtained from, for example,
cancer and non-cancer-bearing individuals.
These distinguishing compounds are known as
biomarkers . Because the majority of published
studies deal with the discovery of cancer
biomarkers, the discussions in this chapter are
limited to cancer biomarker discovery. Many of
the methods described, however, are also appli-
cable to other diseases.
A biomarker is a substance that is overex-
pressed in biological

'

Biomarker
A biomarker is an objectively measured mole-
cule substance that indicates the presence of
an abnormal condition within a patient. A bio-
marker can be a gene (e.g., SNP), protein (e.g.,
prostate-speci

c antigen), or metabolite (e.g.,
glucose, cholesterol, etc.) that has been shown
to correlate with the characteristics of a speci

c
disease. 2 A biomarker in clinical and medical
settings can be used for many purposes,
including early disease detection, monitoring
response to therapy, and predicting clinical
outcome. Biomarkers can be categorized accord-
ing to their clinical applications. In cancer, diag-
nostic markers are used to initially de

fluids or tissues in patients
with a certain disease. A biomarker can include
patterns of single-nucleotide polymorphisms
(SNPs), DNA methylation, or changes in mRNA,
protein, or metabolite abundances. The impor-
tant point is that these patterns correlate with
the characteristics of the disease. 2 Biomarkers

ne the

histopathological classi cation and stage of the

disease, and prognostic markers can predict
the development of disease and the prospect of