Flinders researchers have found proteins in lung fluid that could hold the key to diagnosing pleural mesothelioma months or even years before a tumour is visible on imaging scans.
The Flinders University scientists, some among the world’s leaders in mesothelioma research, examined proteins that help give rise to malignant pleural mesothelioma (MPM) and whether they could be used as biomarkers to identify the cancer earlier. The new study published in the Journal of Proteomics notes that the incidence of mesothelioma is still increasing in many Western countries including Australia even though several of them have instituted asbestos bans. This is largely because of mesothelioma’s long latency period which can sometimes be decades after initial asbestos exposure.
One of the reasons that asbestos cancer is so deadly is that it is usually not identified until it is in an advanced stage, making it less likely to respond to treatment. Many newly-diagnosed mesothelioma patients are told they have only months to live.
Although there are few early mesothelioma symptoms, patients often develop fluid around the lungs months or years before a detectable tumour appears. This is true for several other types of cancer, too, including lung cancer.
Proteins act as communication devices in the body, directing a wide range of critical cellular activities, including the processes that tell cancer cells to begin replicating at a higher rate than normal cells.
By examining the “proteome” or protein profile of this fluid in patients with MPM, lung cancer and benign conditions, the Flinders researchers hoped to find a biomarker for early mesothelioma diagnosis.
“We identified several proteins that may be possible targets and warrant further investigation,” says lead author Reuben White, from Anatomical Pathology at Flinders University’s College of Medicine and Public Health.
Among the key proteins upregulated in the mesothelioma patients were S100 proteins and cytokeratin 5/6. In addition, the researchers concluded that serum amyloid protein-2 “may have a role in prognosis and diagnosis of mesothelioma.” One of the proteins that got special attention in the study is a signal protein called vascular endothelial growth factor (VEGF).
VEGF is known to stimulate the growth of cancer cells and has been found to be up-regulated in the lung fluid of people with mesothelioma.
“Due to the predominance of up-regulated proteins involved in VEGF signalling in MPM, we analysed VEGFA levels in effusions and found a strong correlation between VEGFA levels and survival in MPM,” the paper concludes.
In the study, mesothelioma patients whose proteome included elevated levels of this particular protein did not live as long as those with lower levels.
The next step will be to conduct further studies on the proteins identified in the Flinders research in order to confirm their value as potential mesothelioma biomarkers.
‘Quantitative mass spectrometry to identify protein markers for diagnosis of malignant pleural mesothelioma,’ 2018, by R White, E Pulford, DJ Elliot and LA Thurgood and S Klebe has gone online ahead of print in the Journal of Proteomics (ScienceDirect).
(Source: Flinders University, Journal of Proteomics)