Register TodayEarn Free CME Credits by reading the latest medical newsin your specialty.Sign Up
Glycoprotein fibulin-3 can be used to identify patients with pleural mesothelioma and may be a useful biomarker for the asbestos-related illness, researchers reported.
Plasma levels of the protein were higher in people with the disease than they were in people exposed to asbestos but who did not have mesothelioma, according to Harvey Pass, MD, of New York University Langone Medical Center in New York City, and colleagues.
And levels in effusions from mesothelioma patients were higher than they were in patients with effusions from other causes, Pass and colleagues reported in the Oct. 11 issue of the New England Journal of Medicine.
On the other hand, the researchers cautioned, it's too early to say that the protein can be used for early detection because of a lack of prospective longitudinal studies.
Despite advances in therapy, median survival for pleural mesothelioma remains about a year from diagnosis, the researchers noted.
Earlier detection might help, but "is limited by the long latency period, an inability of imaging to detect the disease at an early stage even when it is used as a screening strategy, and the lack of sensitive and specific blood-based markers."
The latter gap, they hypothesized, might be filled by fibulin-3 if it could be shown to be a "robust biomarker."
To test the idea, they measured fibulin-3 levels in stored plasma samples from 92 patients with mesothelioma, 136 people exposed to asbestos but who did not have the disease, 93 patients with effusions not caused by mesothelioma, and 43 healthy controls.
They also measured levels in stored effusions from 74 patients with mesothelioma, 39 with benign effusions, and 54 with malignant effusions not caused by mesothelioma. Some participants had both types of samples.
The stored samples were collected in Detroit from 1998 through 2005 and in New York from 2005 through 2011, Pass and colleagues reported.
The researchers also conducted two validation analyses – one each using serum and plasma from mesothelioma patients and cancer-free people with asbestos exposure.
Plasma fibulin-3 levels did not vary according to age, sex, duration of asbestos exposure, or degree of radiographic changes.
On the other hand, they were significantly higher in patients with pleural mesothelioma than in asbestos-exposed people without the disease. In the Detroit cohort, mesothelioma patients averaged 105 nanograms per ml of plasma, compared with 13.9 among the asbestos-exposed controls (P<0.001) and in the New York cohort, the respective averages were 112.9 and 24.3 nanograms per ml (P<0.001).
The same was true for fibulin-3 levels in effusions.
In the Detroit cohort, effusion levels averaged 694.4 nanograms per ml higher in patients with pleural mesothelioma and 211.5 in patients with effusion from other causes. In the New York cohort, the respective averages were 636.4 and 150.6 nanograms per milliliter. Both differences were, again, significant at P<0.001.
In the validation study using serum, fibulin-3 levels were unable to discriminate between patients with mesothelioma and those exposed to asbestos but cancer-free, Pass and colleagues reported.
One possible explanation is that the samples, which were collected from 1985 through 1996 during the Carotene and Retinol Efficacy Trial, might have degraded over time, they suggested.
In the other validation study, a set of plasma samples from the University of Toronto showed lower levels in both patients and asbestos-exposed controls than either of the American cohorts – 66.4 and 13.9 nanograms per milliliter, respectively.
But, Pass and colleagues reported, the difference remained significant at P<0.001.
In an overall comparison of patients with and without mesothelioma, the researchers reported, the receiver-operating-characteristic curve for plasma fibulin-3 levels had a sensitivity of 96.7% and a specificity of 95.5% at a cutoff value of 52.8 nanograms per milliliter.
While more research is needed, they concluded, plasma fibulin-3 levels can help tell people with mesothelioma from those who remain healthy after exposure to asbestos.
Together with levels in effusions, plasma fibulin-3 can also differentiate mesothelioma effusions from other malignant and benign effusions, they argued.
The study had support from the Princess Margaret Hospital Foundation, the Princess Margaret Hospital Mesothelioma Research Program (funded by the Masters Insulators Association of Ontario, International Association of Heat and Frost Insulators and Asbestos Workers, Local 793, and other unions, and the Imperial Oil Charitable Foundation), the M. Qasim Choksi Chair in Lung Cancer Translational Research, the Alan B. Brown Chair in Molecular Genetics, the Ontario Ministry of Health and Long-Term Care, Belluck and Fox, the Simmons Foundation, Levi Phillips and Konigsberg, the Stephen E. Banner Fund for Lung Cancer Research, the Rosenwald Family, the Anderson Family, and the NIH.
Pass reported fnancial links with Champions Oncology, Rosetta Genomics, Pinpoint Genomcs, and SomaLogic.
Michael Smith
North American Correspondent
North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.
No comments:
Post a Comment