What do medical tests detect?

Medical tests or studies are frequently used to identify medical conditions. Some tests can identify the presence of a condition before the patient exhibits symptoms. There are many different types of medical tests.

The technical name for things that are measured is a combination of the word 'biological' and 'marker' - biomarkerA biological indicator for a disease or process , for example, the level of a specific protein in the blood that goes up when a disease is present. . The term biomarker "refers to a broad subcategory of medical signs - that is, objective indications of the externally observed medical condition of the patient - which can be measured with accuracy and reproducibility."1 They include simple things like taking a pulse, listening to someone's heart, or taking their blood pressure. Some diagnostic and screening tests, such as those mentioned above, are not invasive. Others involve tests of blood or tissue taken from the patient.

The next sections contain information on some biomarkers used in medical tests, with an emphasis on those used in the diagnosis and detection of cancer.

A biomarker is something that can be found in blood, tissue, or body fluids that can indicate a medical condition, such as disease, infection, or another abnormal condition.2 Biomarkers have quite a few uses, including monitoring patients' response to treatments and whether their disease is progressing. For cancer, many of the biomarkers are substances that are produced by tumor cells or chemicals produced in response to the presence of cancer in the body. Older examples of disease-indicating biomarkers include cancer indicators such as Bence-Jones proteins in multiple myelomaAlso: malignant plasmocytoma. A cancer of the bone marrow in which plasma cells overgrow the normal cells. Plasma cells are B-cells that are fully differentiated and are producing antibodies. patients and carcinoembryonic antigenAny substance capable of being recognized by the immune system. Recognition of such a substance leads to the generation of an immune response. in colon cancer patients.3

Cancer can be detected indirectly by looking at products produced by, or induced by, the cancer. These biomarkers can be found in body fluids or excretions. Different cancers can be detected in different body products.

Biomarkers can be identified in a variety of different ways. They can be found in fluids excreted/secreted from the body, such as feces, urine or sputum. Biomarkers can be also be identified in the blood using minimally invasive tests, such as drawing blood (The Bence Jones proteins mentioned above are found in the urine, and CEA is found in the blood). Some biomarkers are found inside tissues or organs and therefore require a biopsyA medical procedure in which a sample of tissue is removed for examination. Biopsies can range from a small sample drawn into a needle to samples taken during more invasive surgery. or imaging to evaluate them.3

Biomarkers can be discovered in a variety of different ways. Advances in technology used to sequence DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. and identify tiny amounts of proteins have provided a great deal of information on the potential of many different molecules to serve as markers for disease, including cancer.4

Types of Biomarkers

In theory, there are many biological molecules that can serve as indicators of disease. All molecules found in the body that have been altered in some way by disease have the potential to serve as a biomarker. Changes can be changes in the marker structure (called qualitative changes) or in the marker amount (called quantitative changes). Some biomarkers are described below:

Deoxyribonucleic acid (DNA), the carrier of our genetic code, is widely used as a biomarker. Mutations found in proto-oncogenes, which lead to oncogeneA defective gene that is involved in triggering cancer cell growth. Oncogenes are altered forms of genes that normally are involved stimulating cell division. These normal genes are mutated and function in an inappropriate manner in cancer cells. An analogy would be that a mutated oncogene is like a car's gas pedal stuck in the on position. All forms of cancer have one or more mutant oncogenes. Examples of oncogenes that are altered in many cancers are myc, ras and Her-2/neu. Contrast with 'tumor suppressor'. formation, are commonly used to evaluate cancer. Tumor-suppressors, genes that aid in cancer prevention, can also be monitored as biomarkers. Other abnormal genetic changes, such as the number of copies of a particular geneA stretch of DNA that leads to the production of an RNA. The RNA is produced during the process of transcription. This RNA can be used to guide the formation of a protein via translation or can be used directly in the cell. and the fusion of genes that are not normally found together (via translocations) are also used as biomarkers. 3 The source of DNA can be tissue, serum, sputum, saliva, cerebrospinal fluid, or circulating tumor cells (CTCs).

Ribonucleic acid (RNAAlso: ribonucleic acid. RNA is a polymer comprised of the nucleotides A, C, G and U. RNA is the working form of our genetic information. RNA is produced via the process of transcription. Some RNA is used to help build ribosomes (rRNA) and some (mRNA) are used to guide the formation of proteins. Other forms of RNA are used to perform specialized functions in the nucleus.) is very similar to DNA, and changes in RNA may also indicate disease. Small, noncoding RNA molecules, known as microRNAs (miRNAs) are the basis of a growing field of cancer and biomarker research. miRNAs have been identified as markers for many different types of cancer, including colorectal, breast, leukemiaA cancer affecting the cells that develop into white or red blood cells. Both of these cell types originate from stem cells in bone marrow. Red blood cells function to carry oxygen to our tissues and the white cells (leukocytes) are part of our immune system. The cancerous cells often accumulate in the blood., liver, lung, and pancreatic cancer. 5

Proteins are arguably the most important type of biomarker to date. They are responsible for controlling most cellular processes. Proteins may be a more reliable indicator of some conditions because they are created and destroyed rapidly, unlike DNA and some RNA molecules. Proteins can give a real-time indication of the body's condition. 3

Viruses can also serve as biomarkers. Viral infections contribute to about 15-20% of all cancers.  For example, Epstein-Barr virusThe smallest type of organism known. A single virus particle (called a virion) is much smaller than a cell. Viruses reproduce by invading cells and forcing the cells to make progeny virions. Viruses generally have specific host cells which they infect. Some virus types are associated with specific cancers and can convert normal cells into cancer cells. Examples of viruses associated with cancer are: papillomavirus-cervical cancer, hepatitis virus-liver cancer, Epstein-Barr virus-Burkitt's lymphoma. Virus-induced transformation of cells was one of the very first model systems for the study of cancer. Viruses have also been a key tool in the identification of many oncogenes. Because of their great ability to enter target cells viruses such as adenoviruses are being examined for their ability to deliver genes to cancer cells. (EBV) has been linked to carcinomaCancer of epithelial cells, the cells that cover the outside and inside of body surfaces. This is the most common form of cancer. and lymphomaA cancer arising in the lymphatic system. The white blood cells affected are part of the body's immune system. The lymphatic system is a large network of vessels that carry fluid and cells of the immune system around the body. Lymph nodes are regional collection centers in the lymphatic system. See also, 'lymphatic system'.. Human papillomavirus (HPV) has also been showed to be the major cause of cervical cancer and also causes a growing percentage of head and neck cancers. In April of 2014, the FDA approved a HPV DNA test as a primary cervical cancer screening method. 6

BacteriaA microscopic organism. Bacteria lack a nucleus. They are found in very large numbers in almost all locations, including the human body. While most bacteria are harmless or necessary, some can cause disease and death. can also be used as a biomarker. Bacteria that cause chronic, low-level inflammationA reaction to tissue damage or invasion. Small blood vessels become leaky, leading to redness and swelling. Cells of the immune system migrate to the area and can release chemicals and proteins that cause damage to the structures/cells nearby. have been known to cause cancer. For example, H. pylori, a bacterium that inhabits the stomach lining has been linked to the formation of ulcers and stomach cancer. 3

Exosomes are small bubble-shaped structures (vesicles) secreted by cells. They can contain DNA, RNA, miRNA, and/or proteins specific to cancer cells. 7. Exosomes can be found in bodily fluids, such as blood and urine. In many cancers, exosomes have been found to prepare distant sites for metastasis. There are many ongoing efforts examining the use of exosomes as a tool for the diagnosis of cancer and predicting likely cancer outcomes. 8

Cancer cells themselves can be used as biomarkers. Cancer cells circulating the blood stream, known as circulating tumor cells (CTCs), can also be used to provide an indication of disease progression. 9 Cancer stem cells (CSCs) have also been used to monitor disease. CSCs are thought to be a small subset of tumor cells that actively drive tumor growth and spread. 10

Uses of Biomarkers

Biomarkers have several main uses in cancer.

  • Determining what condition a patient has (diagnosis): The goal of using biomarkers as a diagnostic tool is to identify cancer in its early stages. Diagnostic tests can be used to determine the exact nature of a cancer. They may be used to help guide treatment plans.
  • Determining the likely outcome for the patient (prognosis): A prognostic biomarker is used to determine how aggressive the cancer likely to be.
  • Predicting disease progression: A predictive biomarker is used to assess how well a patient will respond to a particular treatment. 3 This type of biomarker can also be used to determine what drugs or chemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division. agents will be most effective for a particular patient. For example, the drugs erlotinib and getfitinib used to treat lung cancer are only effective in patients with a specific mutation in a cell surface proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. - called EGFR. 3
  • Monitoring disease progression: Biomarkers can be used to track how well a treatment is working and guide future treatment decisions.

 

Biomarker Requirements

Despite the fact that many molecules have potential to serve as biomarkers, few have made it to the clinic and gained approval from the U.S. Food and Drug Administration (FDA). To be effective, a biomarker must be able to diagnose early stage tumors and be highly specific to the condition of interest. The molecule must also be present at high enough levels to be detectable. Ideally, the biomarker should be readily found in the blood, serum or other body fluid of affected individuals. Other features include low testing cost, and tests that are easily done. 11, 12

Biomarker Limitations

Although biomarkers have been successfully used to identify and monitor disease, there are trade-offs between sensitivity, specificity, and cost. 13 Sensitivity is the ability of a test to identify people who are affected by the condition. Specificity is the ability of a test to exclude those who do not have the condition.

Learn more about sensitivity and specificity

Another limitation of biomarkers is the possibility of over-diagnosis. Biomarkers may identify cancer that may never have led to symptoms during a person's lifetime. 13 An example of this is prostate specific antigen (PSA), a biomarker for prostate cancer. PSA tests are not able to distinguish between slow growing (indolent) cancers and aggressive cancers that would harm the patient. Because of this limitation, the test is no longer recommended for screening of men at normal risk for prostate cancer. 14

Approved Cancer Biomarkers

List of FDA-approved cancer biomarkers 11

 

 

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