Biomarkers and Blood Tests for Mesothelioma

Page Medically Reviewed and Edited by Anne Courtney, AOCNP, DNP

This page has been fact-checked by a Doctor of nursing practice specializing in Oncology and has experience working with mesothelioma patients.

Sources of information are listed at the bottom of the article. We make every attempt to keep our information accurate and up-to-date.

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Mesothelioma testing is rarely simple or straightforward, and many patients undergo multiple diagnostic tests to confirm or rule out cancer. While imaging and biopsies remain essential, biomarkers and blood tests for many cancer types are gaining interest, including mesothelioma.[1] Research continues to improve the technique of using biomarkers to aid in detecting the presence of cancer.

Biomarkers in the Blood

A biomarker is a molecule of biological origin found in tissues, blood, or other bodily fluids. They are characteristic of some process or disease.[2] Biomarkers are not necessarily bad. For example, certain hormones in urine are biomarkers indicating pregnancy. Biomarkers are also useful in diagnosing diseases, including cancer.

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Pathologists can find various types of biomarkers in the blood to indicate cancer in the body. These include proteins, nucleic acids like DNA and RNA, antibodies, and others.

If there is a biomarker cancer cells are known to produce, its presence in the blood can be part of an overall diagnosis. Some biomarkers are general to all types of cancers. Others may indicate a specific type.[3] Currently, there is no approved biomarker used for mesothelioma screening purposes.

SMRPs and the MESOMARK Assay

One of the most specific biomarkers for mesothelioma is soluble mesothelin-related protein (SMRP). These proteins are produced and released by cancer cells of the mesothelium.

SMRP is normal in mesothelium cells but often overproduced in cancerous cells. The MESOMARK assay is a blood test that measures SMRP levels.[4]

Studies indicate the MESOMARK assay can be a useful diagnostic tool for mesothelioma. Most patients with mesothelioma have elevated levels of SMRPs compared to healthy people.

Unfortunately, this test is not perfect. Some patients with mesothelioma do not have elevated levels. In addition to diagnosing cancer, MESOMARK can also be used to track the progress of mesothelioma. In patients with mesothelioma, levels of SMRP usually go up as the condition worsens.[5]

There is potential for SMRP as a biomarker to act as an early test for mesothelioma. People exposed to asbestos could be screened using the assay to detect rising levels of SMRP early, allowing earlier diagnosis and better treatment options.[6] More research is needed before it’s used for screening purposes.

Another test used to detect mesothelin proteins is the N-ERC/mesothelin test. This test is similar to the MESOMARK assay but can be more accurate thanks to a special enzyme to detect the proteins. It also can be used for other cancers, such as pancreatic and ovarian cancers. While this newer test is more accurate, it is still not a definitive biomarker test.[7]

Fibulin-3

Another biomarker for mesothelioma is the protein fibulin-3. Like SMRP, this protein is released in larger quantities in mesothelioma cancer cells. The protein can be found in blood and pleural fluid.

One early study using fibulin-3 as a biomarker found it was 95% effective at ruling out mesothelioma, and the test was more than 96% more effective at detecting it. Additional research is needed before it can be used for mesothelioma screening.[8]

Osteopontin

Osteopontin is another protein typically found at higher levels in the blood of patients with mesothelioma. There are, however, other types of cancer that also elevate blood levels of this bone-related protein. These include lung cancer, breast cancer, and colon cancer.

Tests for osteopontin may be most useful in screening people with known asbestos exposure. There is a strong connection between the levels of this biomarker and the extent of asbestos exposure. It may be useful in determining how much exposure a person received and, therefore, the level of risk for developing mesothelioma.[9]

Megakaryocyte potentiating factor (MPF)

Another potentially useful biomarker is megakaryocyte potentiating factor or MPF. MPF is a protein made by a precursor of mesothelin.

No one yet understands what MPF does in the body; however, it has been detected at elevated levels in people known to have mesothelioma. Other types of cancer may cause elevated levels of MPF, like ovarian and pancreatic cancer.

One study found levels of MPF changed before and after tumor removal surgery. The amount of MPF in the blood varied depending on how much of the tumor could be removed. This means it could be a useful test for determining how much cancerous tissue remains after surgery.[10]

The Latest in Mesothelioma Biomarker Research

No biomarker is yet a perfect diagnostic factor for mesothelioma. Researchers continue to investigate compounds to improve diagnoses with some potential biomarkers currently under investigation:

High Mobility Group Box 1 Protein. HMGB1 is a protein researchers believe may be diagnositic for mesothelioma. Mesothelioma cells release the protein as they die, triggering an inflammatory response. Studies indicate that a certain form of the HMGB1 could differentiate between healthy asbestos-exposed individuals and those with mesothelioma.[11]
Claudins. This group of proteins are produced in epithelial cells. Researchers have found that claudin-15 is specifically expressed in mesothelial cells. They found the protein in mesothelioma tissue but not in the tissue of other cancers. This protein may help distinguish between mesothelioma and other cancer types.[12]

Tracking Biomarkers in At-Risk Patients

Blood tests for biomarkers have the potential to detect mesothelioma in patients; however, there are limitations. Research continues as scientists seek more accurate tests to diagnose mesothelioma specifically. In the meantime, these biomarker blood tests can help monitor mesothelioma risk in people exposed to asbestos in select cases.

Blood tests for biomarkers will hopefully have a role for routine use in the future. They are still not accurate enough to be utilized for widespread early detection of cancer. The most important thing is to discuss risk factors with your medical care team, and they can help determine the most appropriate screening protocols.

Page Medically Reviewed and Edited by Anne Courtney, AOCNP, DNP

Anne Courtney has a Doctor of Nursing Practice degree and is an Advanced Oncology Certified Nurse Practitioner. She has years of oncology experience working with patients with malignant mesothelioma, as well as other types of cancer. Dr. Courtney currently works at University of Texas LIVESTRONG Cancer Institutes.

Connect with Doctor of Nursing Practice Anne Courtney

References

American Cancer Society. (2018, November 16). Tests for Malignant Mesothelioma.
Retrieved from: https://www.cancer.org/cancer/malignant-mesothelioma/detection-diagnosis-staging/how-diagnosed.html
National Cancer Institute. (n.d.). NCI Dictionary of Cancer Terms. Biomarker.
Retrieved from: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/biomarker
National Cancer Institute. (2019, May 6). Tumor Markers.
Retrieved from: https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
Waknine, Y. (2007, January 29). FDA Approvals: Protege RX, Duet, Mesomark. Medscape.
Retrieved from: https://www.medscape.com/viewarticle/551451
Beyer, H.L., Geschwindt, R.D., Glover, C.L., Hellstrom, I., Hellstrom, K.E., Miller, M.C., Verch, T., Allard, W.J., Pass, H.I., and Sardesai, N.Y. (2007, April). MESOMARK: A Potential Test for Malignant Pleural Mesothelioma. Clin. Chem. 53(4), 666-72.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/17289801
Hollevoet, K., Reitsma, J.B., Creaney, J., Grigoriu, B.D., Robinson, B.W., Sherpereel, A., Cristaudo, A., Pass, H.I., Nackaerts, K., Rodriguez Portal, J.A., Schneider, J., Muley, T., Di Serio, F., Baas, P., Tomasetti, M., Rai, A.J., and van Meerbeeck, J.P. (2012, May). Serum Mesothelin for Diagnosing Malignant Pleural Mesothelioma: And Individual Patient Data Meta-Analysis. J. Clin. Oncol. 30(13), 1541-49.
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383122/
Imashimizu, K. Shiomi, K., Maeda, M., Aoki, N., Igarashi, K., Suzuki, F., Koizumi, M., Suzuki, K., and Hino, O. (2011). Feasibility of Large-Scale Screening Using N-ERC/Mesothelin Levels in the Blood for the Early Diagnosis of Malignant Mesothelioma. Exp. Ther. Med. 2(3), 409-11.
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440716/
Pass, H.I., Levin, S.M., Harbut, M.R., Melamed, J., Chiriboga, L., Donington, J., Huflejt, M., Carbone, M., Chia, D., Goodglick, L., Goodman, G.E., and Thornquist, M.D. (2012, October 11). Fibulin-3 as a Blood and Effusion Biomarker for Pleural Mesothelioma. N. Engl. J. Med. 367, 1417-27.
Retrieved from: https://www.nejm.org/doi/full/10.1056/NEJMoa1115050
Creaney, J., Yeoman, D., Demelker, Y. Segal, A., Musk, A.W., Skates, S.J., and Robinson, B.W. (2008, August). Comparison of Osteopontin, Megakaryocyte Potentiating Factor, and Mesothelin Proteins as Markers in the Serum of Patients with Malignant Mesothelioma. J. Thorac. Oncol. 3(8), 851-7.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/18670302
Onda, M., Nagata, S., Ho, M., Bera, T.K., Hassan, R., Alexander, R.H., and Pastan, I. (2006, July). Megakaryocyte Potentiation Factor Cleaved from Mesothelin Precursor Is a Useful Tumor Marker in the Serum of Patients with Mesothelioma. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-06-0472
Retrieved from: https://clincancerres.aacrjournals.org/content/12/14/4225
Ahmadzada, T., Reid, G., Kao, S. (2018, April 10). Biomarkers in Malignant Pleural Mesothelioma: Current Status and Future Directions. J. Thorac. Dis. 10(Suppl9), S1003-S1007.
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5949443/
Watanabe, M., Higashi, T., Ozeki, K., Higashi, A.Y., Sugimoto, K., Mine, H., Takagi, H., Ozaki, Y., Muto, S., Okabe, N., Matsumura, Y., Hasegawa, T., Shio, Y., Suzuki, H., and Chiba, H. (2021, June 15). CLDN15 is a Novel Diagnositc Marker for Malignant Pleural Mesothelioma. Scientific Reports. 11(12554), https://doi.org/10.1038/s41598-021-91464-0.
Retrieved from: https://www.nature.com/articles/s41598-021-91464-0

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