How Does the Proteome Compare to the Genome?
The biggest conceptual challenge inherent in proteomics lies in the proteome's
increased degree of complexity compared to the genome. For example:
- One gene can encode more than one protein. The human
genome contains about 21,000 protein-encoding genes, but the total number
of proteins in human cells is estimated to be between 250,000 to one million.
- Proteins are continually moving and undergoing changes such as binding to a
cell membrane, partnering with other proteins, or breaking into two or more
pieces. The genome, on the other hand, is relatively static.
- Cells are continually modifying proteins once they are produced. As a result,
the types of proteins measured can vary considerably from one person to
another, under different environmental conditions, or even within the same
person at different ages or states of health.
- Proteins exist in a wide range of concentrations in the body. For example, the
concentration of the protein albumin in blood is more than a billion times
greater than that of interleukin-6, making it extremely difficult to find the
low- abundance proteins in a mixture.
Implications of Proteomics for Medical Practice
"The world of personalized medicine today is very gene-centric. This is not surprising
given that genomic studies are among the most promising strategies to help advance
personalized medicine efforts. However, while genomics will always remain a
cornerstone of personalized medicine, these studies alone cannot capture the complete
view of disease processes.
 |
|
While genes are the 'recipes' of the cell, containing
all of the instructions for assembly, proteins are the
products of these recipes, functioning as the cellular
"engines" that drive both normal and disease
physiology. So while genomics may provide the
likelihood of developing a certain disease, proteins
may diagnose what is happening in a patient in real
time.
Together, these complementary fields (genomics
and proteomics) are absolutely necessary for
understanding the molecular underpinnings of
disease and for enabling personalized medicine." - Quote from National Cancer Institute |
|
|
|
What Proteomics Means for People
A breakthrough in future cancer treatment was the discovery that tumors "leak"
proteins and other molecules into blood, urine, and other accessible bodily fluids.
This insight has led to the possibility of diagnosing cancer at an early stage simply by
collecting such fluids from patients and testing them for the presence of cancer-related
molecules, also called "cancer biomarkers/tumor markers". The greatest promise for
the early detection and treatment of cancer lies in the ability to find valid molecular
indicators, or biomarkers, of the disease.
Progress in cancer genetics has been rapid, but this provides us with only a glimpse of
what may occur. We need to measure what is happening inside a patient in real time,
and that means finding tell-tale protein biomarkers. This is because genes are only the "recipes" for the cell. The proteins encoded by the genes are ultimately the critical
molecular players that drive both normal and disease physiology.
The earlier a patient's cancer is diagnosed the more treatable it is by surgery, radiation
or chemotherapy. Biomarkers found in blood and other fluids might also be valuable
for monitoring the response of cancer during treatment or detecting the recurrence of
tumors after treatment.
Certain blood proteins are already being used as cancer biomarkers.
Here are two examples:
- Prostate specific antigen (PSA): Elevated levels may suggest the presence of
prostate cancer.
- Cancer antigen 125 (CA-125): Elevated levels suggest recurrent ovarian cancer.
|
|
|
 |
|
Unfortunately, both tests may result in:
False negatives - failure to detect cancer in
those who have it (poor sensitivity), or
False positives - a positive test result for the
presence of cancer in people who are actually
cancer-free (poor specificity). |