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Genetics Affect Accuracy of SMRP Test for Mesothelioma

ByAlex Strauss
SMRP test for mesothelioma

The SMRP test for mesothelioma is a tool doctors use to help diagnose asbestos cancer and plan treatment. But new research suggests that the test is not as useful as it could be due to genetic variability. 

Slovenian doctors say a person’s genetics influence how much SMRP they produce. 

Based on their research, they recommend combining the SMRP test for mesothelioma with genetic testing. Their findings suggest the combination method produces a more accurate and useful mesothelioma biomarker.

What is the SMRP Test for Mesothelioma?

SMRP stands for soluble mesothelin-related peptides. They are produced when proteins found in the mesothelial membranes start to break down. Malignant mesothelioma is one condition that can trigger this breakdown. 

As a mesothelioma tumor grows and the protein mesothelin breaks down, SMRP levels climb. These SMRPs end up in the blood serum and lung fluid of mesothelioma patients. 

The main SMRP test for mesothelioma is the MESOMARK assay. The test looks for abnormally high levels of SMRP in the blood. 

Unfortunately, mesothelioma diagnosis is not as simple as a blood test. Some types of mesothelioma tumors do not release high levels of SMRP. And, as the current study shows, SMRP levels can also vary naturally from one patient to the next. 

This makes it tricky to know if an SMRP test for mesothelioma is positive or just normal for that patient. The Slovenian researchers say the ranges that doctors normally use are probably too broad. Taking genetics into account could help. 

The Influence of Genetics on SMRP Levels

The new study focused on a gene called MSLN rs1057147. MSLN is the gene that encodes for the protein mesothelin. 

Researchers looked for abnormalities on the MSLN gene and ran an SMRP test for mesothelioma on 782 people. All of the subjects were exposed to asbestos but only 154 of them had malignant mesothelioma. 

Every gene contains two alleles – one from each parent. Among the people who did not have mesothelioma, those who had an abnormality on one or both of their MSLN alleles had much higher SMRP levels. This was not true of the mesothelioma patients. 

All of the mesothelioma patients had higher-than-normal SMRP levels. Among those with at least one abnormal allele, survival was significantly shorter. 

When researchers combined the genotype test with the SMRP test for mesothelioma, the ability of the test to rule out mesothelioma (specificity) improved from 88.5% to 92.7%.

“MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of malignant mesothelioma patients,” say the researchers. “Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.”

SMRP is not the only biomarker for mesothelioma. Some others are osteopontin, fibulin-3 (FBLN3), neutrophil to lymphocyte ratio, c-MET expression, and ki-67 ratios. FBLN3 is most often used for mesothelioma prognosis rather than diagnosis.

Sources:

Goricar, K, “Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases”, March 7, 2020, Radiology and Oncology, https://www.ncbi.nlm.nih.gov/pubmed/32187018

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