Exam Tips, Certification Exam Guides, Microsoft Exam Tips, CISCO Exam Tips: Biomarker

Tuesday, 18 June 2013

Biomarker for Asbestos-Linked Cancer Works (CME/CE)

Earn Free CME Credits by reading the latest medical news
in your specialty.

By Michael Smith, North American Correspondent, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerThis study suggests that plasma fibulin-3 levels can distinguish healthy persons with exposure to asbestos from patients with mesothelioma.The study also suggests that in conjunction with effusion fibulin-3 levels, plasma fibulin-3 levels can differentiate mesothelioma effusions from other malignant and benign effusions.

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.

Old Biomarker May Have New Role in Lung Ca (CME/CE)

Earn Free CME Credits by reading the latest medical news
in your specialty.

By Kathleen Struck, Senior Editor, MedPage Today Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse PlannerNote that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.Smokers with low bilirubin levels were at increased risk for lung cancer incidence and mortality compared with those who had the highest bilirubin levels, suggesting that serum bilirubin may be able to function as a potential biomarker for lung cancer risk prediction.

WASHINGTON -- Bilirubin, which is considered a useful liver function marker, may also point to smokers at increased risk for lung cancer.

In a large Taiwanese prospective cohort, male smokers with bilirubin in the lowest quartile lowest had a 69% higher risk for developing lung cancer, and a 76% higher rate of lung cancer mortality, compared with male smokers who had the highest bilirubin levels, said Xifeng Wu, MD, of the University of Texas MD Anderson Cancer Center in Houston.

In men who had never smoked, bilirubin levels had no significant effect on health outcomes.

The research showed that serum bilirubin is a potential biomarker for lung cancer risk prediction, Wu told MedPage Today at the annual meeting of the American Association for Cancer Research.

"It was kind of a surprise and very interesting," Wu said. "The biomarker was identified from metabolic profiling and validated by the large, cohort study."

In the Taiwanese cohort of 435,985 individuals, the incidence rate of lung cancer in men with bilirubin levels of 0.68 mg/dL or less was 7.02 per 10,000 person-years irrespective of smoking history. This compared with a rate of 3.73 per 10,000 person-years in men whose bilirubin levels were 1.12 mg/dL or more, again irrespective of smoking history.

Wu said this translated into a 51% increase in the risk for developing lung cancer for low-bilirubin patients.

Also, the lung-cancer specific mortality rate in men with low bilirubin was 4.84 per 10,000 person-years compared with 2.46 per 10,000 person-years in men with high bilirubin.

When only male smokers were analyzed the associations were starker -- a 76% increase in lung cancer mortality.

Wu said she first conducted global, unbiased metabolomic profiling in serum samples from 20 healthy controls, 20 patients in early-stage lung cancer, and 20 patients in late-stage lung cancer. Matching for age and gender, Wu selected three differentially expressed metabolites for validation in two case-control populations. Bilirubin emerged and was validated by the large Taiwanese prospective cohort.

Wu said the study focused on male smokers and was limited by an insufficient amount of female smokers from which to draw conclusions.

But the research does point to the potential benefit of using biomarkers in cancer research, she said.

"We need to identify additional biomarkers, including metabolomic biomarkers," Wu said.

"It's a very large study and brings up interesting findings that to my knowledge haven't been reported before," said Lecia Sequist, MD, of Massachusetts General Hospital in Boston. "This will generate a lot of interesting future research in biologic relations between bilirubin and lung cancer."

The authors had no disclosures.

Primary source: American Association for Cancer Research
Source reference:
Wu X, et al "Metabolomic profiling identifies bilirubin as a novel serum marker for lung cancer" AACR 2013; Abstract LB-27.

Kathleen Struck

Senior Editor

Kathleen Struck joined MedPage Today after serving as Managing Editor for EverydayHealth.com, Stars and Stripes and MediaNews Group. She lived and traveled internationally for more than 15 years and has written and edited for publications including, Washington Post, Baltimore Sun, Newsday and Regulatory Affairs Professional Society. At MedPage Today, she reports and edits on general news and information.