Protein Biomarker Assays for Diagnosing Thyroid Cancer May Show Inaccurate Readings

Protein biomarkers are used to test for cancer before and after tumor resections. To test thyroid malignancy, many biomarkers are tested separately to confirm cancer. However, new research shows that the tests used to measure 2 major biomarkers in the diagnosis of thyroid cancer may be inaccurate. The study was recently published in Thyroid (2015; 10.1089/thy.2015.0105).

One biomarker, thyroglobulin (Tg), is a glycoprotein that has sugar in its molecular structure. Research leader Tarun Dam, PhD, an assistant professor of chemistry at Michigan Technological University in Houghton, described it as candy-coated. He points out that the second biomarker, galectin-3 (Gal-3) is not a glycoprotein, but has a sweet tooth.

Like a kindergartner on Halloween, Gal-3 cannot resist Tg. The two proteins tend to clump, an interaction not accounted for in the current thyroid cancer detection assays.

The clumping cycle of Tg and Gal-3 is fairly straightforward from a biomechanics perspective. A thyroid cancer cell secretes Tg and Gal-3, and the sweet tooth nabs the glycoprotein, as Gal-3 binds Tg. As more Tg is secreted, the influx partially breaks up the larger clumps. The body can potentially remove some globs quickly, taking away some of the biomarkers before a sample is collected from a patient.

Currently, detection assays only look at Tg and Gal-3 separately. They have no way to account for the biomarkers that may be tied up or removed in clumps. Plus, there is no way to know what stage of the clumping cycle the proteins are in; they could be in a big clump, already metabolized, partially dissolved, or mostly free.

Dam and his team tested the physical and biochemical properties of the biomarkers to ensure this clumping cycling was driven by the proteins' interactions.

Based on his team's findings, Dam suggests adding a step to break up the clumps before running the assay tests, which should help make the tests more accurate.

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