Japanese researchers have demonstrated that the modified form of the HEG1 protein is a highly specific marker and a useful diagnostic tool for malignant mesothelioma (MM). The protein is also linked to MM proliferation, indicating that it could be a possible therapeutic target to treat the disease.
MM is a fatal tumor caused by past exposure to asbestos. Globally, some 125 million people have been exposed to asbestos on the job, and are at risk of developing MM. In Japan, some 1,300 people die each year of MM; the earthquake and tsunami that struck Japan in 2011 destroyed more than 100,000 houses, further scattering asbestos dust.
Shoutaro Tsuji of the Kanagawa Cancer Center Research Institute in Yokohama, along with his colleagues, found that HEG1 — under the influence of a non-genetic modification — was specifically expressed in MM tissue samples and could not be detected in normal major tissues.
With the use of a specific antibody, called SKM9-2, that identifies the modified form of HEG1, they could detect MM samples with a false-positive rate of only 8 percent. These results were further tested in 24 primary samples of non-mesothelioma related tumors, in which the observed low expression of the protein confirmed the specificity of this protein for MM.
In addition, SKM9-2 use could also identify 92 percent of malignant pleural mesothelioma (MPM) samples, 64 percent of sarcomatoid, and 50 percent of desmoplastic MPMs samples. Compared to current existing diagnostic markers, this new tool improved the positive detection rate and allowed the identification of MM subtypes that currently lack identification markers.
It is still unclear what the function of HEG1 is, or the importance of its non-genetic modification. Due to its structural resemblance to the mucins protein family, the authors hypothesized that HEG1 could have a mucin-like activity.
Previous studies showed that mucins were involved in survival and proliferation of cancer cells. Inhibition of HEG1 in mesothelioma cells was found to block their replication capacity, suggesting that this protein expression is involved in MM cell proliferation and in part confirming its mucin-like physiological activity. Cells with low levels of HEG1 were not affected by inhibition of its activity, indicating that MM cells’ proliferation rate depends more on HEG1, according to their HEG1 protein expression levels.
“In light of the association between HEG1 and mesothelioma proliferation, the mAb [antibody] SKM9-2 and HEG1 may be productive diagnostic tools and therapeutic targets for MM,” Tsuji and colleagues wrote.