A website to provide support for people who have or have had any type of cancer, for their caregivers and for their family members.
Results 1 to 1 of 1

Thread: Proteomics and Cancer

  1. #1
    Newbie New User
    Join Date
    Apr 2012

    Proteomics and Cancer

    What is proteomics?
    The term proteome refers to the totality of the proteins in a cell, tissue, or organism. Proteomics is the study of these proteins—their identity, their biochemical properties and functional roles, and how their quantities, modifications, and structures change during development and in response to internal and external stimuli. The field of proteomics has been propelled by advances in mass spectrometry and other techniques that have made it possible to analyze proteins in large numbers of biological samples rapidly and at low cost.

    Proteins are products of the genetic code (DNA), and they drive the workings of cells, tissues, and organs. The proteins produced in a specific cell determine that cell’s function in the body.

    The human proteome—like the proteomes of all organisms—is dynamic, changing constantly in response to the needs of the body. It differs widely between people depending on factors such as age, sex, diet, level of exercise, and sleep cycle. The proteome also changes in response to cancer and other diseases, making the proteome of great interest to medical researchers.

    For example, cancer cells often secrete specific proteins or fragments of proteins into the bloodstream and other bodily fluids, such as urine and saliva. Researchers hope to discover groups or patterns of proteins—called protein signatures—in these easily accessible fluids that provide information about the risk, presence, and progression of diseas. This knowledge could ultimately help doctors better detect cancer before symptoms are present and customize treatment to the individual patient.

    How is proteomics different from studying genes (genomics)?
    The proteome of an organism is much larger and more complex than its genome. Many genes have the potential to produce more than one version of the protein they encode. In addition, proteins are frequently modified by cells after they are made.

    Protein modifications include the addition of various chemical groups, such as phosphate, acetate, and methyl groups, or the addition of carbohydrate (sugar) and lipid (fat) molecules. These modifications help regulate the function of proteins, as well as their location inside or outside of cells. Taking protein modifications into account, it has been estimated that the human body may produce more than 1,000,000 different protein species from its 20,000 to 25,000 protein-coding genes.

    This higher level of complexity is compounded by the fact that the protein composition of an organism or a tissue changes constantly as new proteins are made, existing proteins are eliminated, and proteins become modified or demodified in response to internal and external stimuli. In contrast, a person’s genome remains relatively unchanged over the course of his or her lifetime.

    What techniques and technologies are used in the study of proteomics?
    Two main approaches are currently used in cancer proteomics research: Protein identification and pattern recognition.

    For protein identification, researchers can use several different techniques. For example, based on what is known about the biology of a certain type of cancer, researchers can select antibodies that bind to proteins thought to be overexpressed in that cancer type. These antibodies are then placed into wells on a protein microarray (similar to a DNA gene-expression microarray, sometimes called a ‘gene chip’), and a sample of the fluid being tested (such as blood or urine) is washed over the microarray. If present, the proteins will bind to the antibodies and can be detected by a technique known as fluorescence microscopy. The amounts of these proteins found in samples taken from patients with cancer can be compared with those from patients without cancer.

    Gel-based electrophoresis techniques can also be used to isolate proteins of interest. Gel electrophoresis is a technique that separates proteins based on their mass and electrical charge. Once proteins that are more abundant in cancer patients have been isolated using this method, they can be identified by an enzyme-linked immunosorbent assay (ELISA). ELISA uses antibodies to identify proteins in a manner similar to microarrays.

    For pattern recognition, a technique called mass spectrometry (MS) can be used to measure the masses and relative quantity of all proteins in a particular biological sample. MS machines can produce protein profiles (signatures) that can be compared between samples taken from patients with and without cancer, but they cannot identify the individual proteins that produce the signatures.

    Other technologies include chromatography and a different type of MS, called tandem MS, which can be used to identify individual proteins in an MS signature. Identification of the actual proteins that create a protein signature identified by mass spectrometry is important because it reduces the likelihood that differences in protein signatures observed between biological samples taken from patients with and without cancer are actually due to bias. Differences in the way samples from patients with cancer (cases) and from those without (controls) are handled during collection, storage, or processing can all introduce bias—the appearance of a difference in proteins between cases and controls due to cancer when no difference actually exists.

    Both protein identification and pattern recognition research also require high-powered computing and bioinformatics systems to process the enormous amount of data that are produced by these studies.

    Confidence in the results of proteomics studies and identified biomarker signatures will require promising results to be reproduced in different populations and by different laboratories, a process called validation.

    What technical challenges must be overcome to advance proteomics research?
    Proteomics research is currently limited by the technologies that are available for analyzing proteins. For example, mass spectrometers can accurately measure very small amounts of protein—proteins that are 1 in 100 to 1 in 10,000 times less common than other proteins in a sample of tissue or bodily fluid; however, proteins produced by cancer cells are often present in even smaller quantities, making their detection difficult. Researchers are working to improve the sensitivity of mass spectrometry to allow scientists to detect these rare cancer proteins.

    In addition, research programs, including the National Cancer Institute’s (NCI) Antibody Characterization Program , are developing antibodies and other molecules called affinity reagents to accurately identify proteins in blood and tissue samples taken in the clinic; however, the production of these molecules still lags behind the needs of researchers. This lack of antibodies slows both protein identification research (which requires antibodies to indicate the presence of known proteins in biological samples) and pattern recognition research (researchers can use antibodies to identify the proteins that make up a protein signature detected by MS).

    Another challenge is that proteins are more likely to be degraded or otherwise altered during isolation, storage, and handling than molecules such as DNA. Therefore, stringent precautions are needed to maintain the integrity of proteins to ensure proteomics research results are accurate. To address this issue, researchers are developing best practices and standardizing procedures for collecting, processing, storing, and sharing tissue and bodily fluid specimens, which are collectively known as biospecimens.

    Ultimate confirmation of the existence of individual protein biomarkers or protein signatures and their association with specific types of cancer—a process known as biomarker validation—will require the reproduction of findings in different laboratories and additional populations of patients

    Last edited by Didee; 04-10-2012 at 09:37 AM.


Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts