Thyroid Cancer Assays May Be Skewed by Biomarker's Proverbial Sweet Tooth

November 20, 2015
Cate Douglass

A research team from Michigan Technological University recently discovered two major biomarkers used in the detection of thyroid cancer may be inaccurate in diagnosing the disease.

Tarun K. Dam, PhD

A research team from Michigan Technological University recently discovered two major biomarkers used in the detection of thyroid cancer may be inaccurate in diagnosing the disease, according to a Michigan Tech news release.1The study found that two biomarkers, thyroglobulin (Tg) and galectin-3 (Gal-3) bind together, and as a result, alter the assays that are often used for detection.

According to Tarun K. Dam, PhD, an assistant professor of chemistry at Michigan Tech, Tg is a glycoprotein that has sugar in its molecular structure and is often thought of as “candy-coated.” While Gal-3 is not a glycoprotein, Dam said that it has a “sweet-tooth.”1

Essentially, a thyroid cancer cell secretes both biomarkers at the same time and Gal-3 binds to Tg during a clumping cycle—one Tg can hold as many as 14 glycoproteins.2As more Tg is released from the cancer cell, the mass begins to break up into smaller pieces that the body can dispel.

However, if the body can remove the leftover clumps, it removes evidence of biomarkers before samples can be taken from patients. The study noted that this binding of Tg and Gal-3 has the potential to influence the biological functions of the individual biomarkers, which impedes clinical detection.2

In order to understand whether this clumping cycle is caused by the protein’s interactions, the Michigan Tech research team studied the physical and biochemical properties of the biomarkers.

The quick turnaround of the clumping cycle makes it difficult for researchers to determine where the biomarkers are in the process. The team also found that similar problems have occurred in thyroglobulin autoantibodies (TgAb), which form a Tg-TgAb clump.

Current assay tests examine each biomarker separately, so the exams have no way of accounting for the proteins that are either clumped together or that have already been removed, according to the news release.

Dam et al suggested that adding an extra step in the process by breaking up the clumps before running the detection tests can improve the accuracy of the exam. While Dam said that he believes this small change could make a difference, he plans on continuing to observe this clumping cycle in thyroid cancer cells and to expand his research.

The team noted that the biomechanical interactions demonstrated in thyroid cancer biomarkers could also happen in other types of cancers, including ovarian, breast, lymphoma, and prostate, among others.

“The lesson is before you make a final conclusion, make sure the sample did not a have cluster,” Dam said in a statement. “This is biophysics, it’s not theoretical, and many kinds of cancer biomarkers are candy-coated glycoproteins and most of these cancer cells also produce the sweet tooth Gal-3.”

References

  1. Michigan Tech News. Thyroid cancer biomarker assays may show inaccurate readings. 2015. http://www.mtu.edu/news/stories/2015/november/thyroid-cancer-biomarker-assays-may-show-inaccurate-readings.html. Accessed November 19, 2015.
  2. Ncbi.nlm.nih.gov. Glycan-dependent mutual and reversible sequestration of two thyroid cancer biomarkers. - PubMed - NCBI. 2015. http://www.ncbi.nlm.nih.gov/pubmed/26421933. Accessed November 20, 2015.