New Biomarker May Allow Earlier Diagnosis of Mesothelioma
CT scan of the chest showing a malignant mesothelioma (Image by Dr. Tomas Dvorak, MD Anderson Cancer Center Orlando)
Pleural mesothelioma, a disease of the tissue that lines the chest cavity and covers the lungs (the pleura), is an aggressive cancer often associated with asbestos exposure. Patients diagnosed with this disease have a median survival of 1 year.
Diagnosing mesothelioma early, when treatment may be most effective, is difficult because of its long latency period and the lack of reliable methods to detect the disease in its early stages. A protein called soluble mesothelin-related protein is the best-studied biomarker for mesothelioma, but the test for it has low sensitivity, meaning that it fails to detect mesothelioma in some people who have the disease.
In the study, supported by NCI’s Early Detection Research Network (EDRN), Dr. Harvey Pass of the New York University Langone Medical Center and his colleagues identified fibulin-3, a protein important in cell-to-cell and cell-to-extracellular matrix signaling, as a potential mesothelioma marker.
The researchers measured fibulin-3 levels in plasma and pleural effusion samples from 142 patients with mesothelioma, 136 cancer-free individuals exposed to asbestos, and 93 patients with effusions not due to mesothelioma. The researchers also evaluated plasma samples from 91 patients with cancers other than mesothelioma, as well as from 43 healthy control subjects, many of whom were EDRN investigators.
Average plasma fibulin-3 levels were higher in patients with mesothelioma than in people without cancer who had been exposed to asbestos. Patients with mesothelioma and those without the disease could be distinguished with a sensitivity of 96.7 percent and a specificity of 95.5 percent at a cutoff level of 52.8ng/ml of plasma fibulin-3.
The researchers used another cohort of plasma samples to validate their findings, though the sensitivity and specificity fell to 72.9 percent and 88.5 percent, respectively.
“This is a totally new marker; something that we have never thought about in mesothelioma,” commented Dr. Raffit Hassan of NCI’s Center for Cancer Research, who was not involved in the study. “Fibulin-3 appears to be much better than serum mesothelin in terms of sensitivity and specificity.”
Plasma fibulin-3 levels may also be helpful in monitoring response to therapy and disease progression. In 18 patients, fibulin-3 levels fell after surgery, and there was a trend toward rising fibulin-3 at the time of disease progression in 6 of these patients.
Fibulin-3 levels were higher in effusion samples than in plasma samples. In the few patients with both plasma and effusion samples, there was no clear relationship between the fibulin-3 levels in the two locations. Effusion fibulin-3 levels, however, were able to distinguish patients with mesothelioma from those with effusions not related to the disease, a welcome finding as it is difficult to distinguish patients with mesothelioma from those with benign effusions or malignant effusions due to other cancer types.
Likewise, effusion fibulin-3 levels were lower in patients with stage I or II mesothelioma than in those with stage III or IV disease. Patients with the highest effusion fibulin-3 levels at the time of surgery had shorter survival times.
The results are promising, though more studies involving a larger number of patients and prospective studies are needed to validate fibulin-3 as a biomarker for mesothelioma, noted Dr. Hassan.
“The other important thing would be to see if the levels of fibulin-3 could be used as a biomarker for response to chemotherapy or other biological therapies,” he said. “Since mesothelioma is a very difficult disease to measure radiologically, it would be nice to have a sensitive and specific assay for monitoring response to treatment.”
—Jennifer Crawford
This research was supported by grants from the National Institutes of Health (U01 CA-111295 and U01 CA-113913).
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