New HMGB1 Blood Test Could Detect Mesothelioma Early

Illustration of mesothelioma research

A promising recent study published in the journal Clinical Cancer Research has shown that a blood test that can speed the diagnosis of mesothelioma. Diagnosis is often delayed and usually requires surgery to obtain a tissue sample for examination, and early identification of mesothelioma has been shown to be one of the best ways to improve the effectiveness of treatment. As such, researchers have been working to develop new blood tests to diagnose mesothelioma, and this study shows that a blood protein commonly referred to as HMGB1 can be used with near 100% accuracy.

The abstract of the study concludes:
Our results are significant and clinically relevant as they provide the first biomarker of asbestos exposure and indicate that hyperacetylated HMGB1 is an accurate biomarker to differentiate malignant mesothelioma patients from individuals occupationally exposed to asbestos and unexposed controls.

How HMGB1 Detects Asbestos and Mesothelioma

Mesothelioma is a cancer that affects the mesothelium, a tissue lining that covers the chest and abdominal cavities. Since asbestos fibers typically enter the body by being breathed in through the air, about 80% of mesothelioma cases primarily affect the lungs when the disease develops. It is also a rare disease that takes from 20 to 50 years or more from when exposure to asbestos occurs until mesothelioma develops. The initial symptoms such as pain, shortness of breath or fluid around the lungs can be caused by other more common illnesses such as COPD, pneumonia or bronchial infections.

Three different blood tests have been used to measure substances (known as “biomarkers”) that are elevated when mesothelioma is suspected. However, the biomarker tests developed thus far have not been accurate enough to confirm the diagnosis of mesothelioma without also doing a surgical biopsy.

High mobility group box protein 1 (HMGB1) is a new biomarker that has shown in clinical trials to be an accurate predictor of past exposure to asbestos. Using evidence from previous studies, the authors believe that HMGB1 plays a role in the development of mesothelioma in two ways. Foremost, HMGB1 is released by cells damaged by the chronic presence of asbestos fibers. Furthermore, they believe that once the damage from asbestos turned into mesothelioma, the cells continue to release HMGB1 while undergoing a process called “acetylation,” which differentiates mere asbestos exposure from cancerous growths. The HMGB1 that has been “acetylated” by mesothelioma cells is referred to as “hyperacetylated HMGB1”.

The study used different groups of people to test both if HMGB1 could predict past exposure to asbestos and if a person had mesothelioma:

  • Healthy people who had never been exposed to asbestos. The study found low levels of any form of HMGB1.
  • Healthy people who were known to have been exposed to asbestos in the past. The study found high levels of HMGB1, but low levels of the hyperacetylated type.
  • People with respiratory (pleural) mesothelioma. The study found the very high levels of both types of HMGB1.

Mesothelioma that affects the lungs often causes a buildup of fluid – known as pleural effusion – between the lungs and the chest wall, often causing shortness of breath, pain, or weakness. The study tested patients with pleural effusion fluid caused both by mesothelioma and by other illnesses. Once again, the study found that testing the different HMGB1 levels was very good at identifying mesothelioma, since the biomarker did not appear with other conditions.

Comparing HMGB1 to Other Biomarker Tests

The study also compared HMGB1 to the other three blood tests that are currently being used to help test for asbestos exposure and mesothelioma. Essentially, the study found that HMGB1 testing was much better than all of the other tests in detecting asbestos exposure. It also found that HMGB1 testing was better than two of the existing blood tests for diagnosing mesothelioma. If combined with the third blood test called fibulin-3, the two were better together in diagnosing mesothelioma in patients with fluid in the chest than either one alone.

Previous studies have shown a link between HMGB1 levels and non-small cell lung cancer (NSCLC). A meta-review of fifteen studies found a link was found between HMGB1 levels and NSCLC, and that different levels could even be used to determine what stage the cancer was at. Non-small cell lung cancer and mesothelioma are different, but since they both affect the lungs, challenges in proper diagnosis and treatment are often very similar.

Further research about HMGB1 testing and mesothelioma are needed to help doctors with early diagnosis and better treatment. Over 30% of mesothelioma cases are in military veterans who were exposed to asbestos during their service time. Given this situation, the Department of Defense has provided over $3 million to the University of Hawaii for further research in several different areas:

  • Confirming that HMGB1 levels can be used to detect past exposure to asbestos and early diagnosis of mesothelioma.
  • Using HMGB1 research to help find genes that are related to increased risk of developing mesothelioma.
  • Developing a vaccine against developing mesothelioma in people who were exposed to asbestos.

Mesothelioma is typically not diagnosed until it has reached an advanced stage. At that point, treatment is less effective. The ongoing search for better ways to detect and treat mesothelioma earlier continues to break new ground. This will help in developing better treatment and prognosis for patients and ultimately save lives.