Despite decades of warnings about smoking, lung cancer is still the second-most common cancer and the leading cause of death from cancer in the United States. Diagnosis is often made only when the disease is already at an advanced stage and hard to treat. Researchers are trying to change that by identifying biomarkers that could be the basis of early tests for lung cancer.
“Early diagnosis is the key to fighting lung cancer,” said Oliver Fiehn, PhD, director of the metabolomics center and a professor of molecular and cellular biology at the West Coast Metabolomics Center at the University of California Davis.
Lung cancer can be diagnosed early with regular low-dose CT (computed tomography) scans in people at risk. However, these tests are very expensive, and they also involve exposing patients to radiation. Instead, Fiehn, project scientist William Wikoff, PhD, and colleagues set out to look for biomarkers of developing lung cancer in blood from patients.
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Fiehn’s laboratory specializes in metabolomics, an approach that involves analyzing all the biochemical products of metabolism in cells and tissues at the same time. Like other -omics approaches, it is made possible by new technology and computing power, and it is opening up new ways to understand living processes.
To find early biomarkers for lung cancer, the team needed to look at blood samples collected from people who developed the disease months or years before their diagnoses. Fortunately, they were able to access samples stored from the CARET clinical trial. The CARET study, which ran from 1985 until it was halted in 1996, attempted to test whether doses of antioxidant vitamins could prevent cancer in heavy smokers and other people at high risk. The trial failed, but the collection of blood, serum, and tissues and related data are maintained as the CARET Biorepository.
Applying metabolomics, Wikoff and Fiehn found that one molecule, diacetylspermine, was almost doubled in serum collected from patients up to 6 months before their lung cancer was diagnosed, compared with healthy controls.
They then combined diacetylspermine with another previously identified biomarker, a protein called pro-surfactant protein B (pro-SFTPB), and tested for both markers in another set of sera collected from CARET patients months before they developed lung cancer.
“Individually, the markers were about 70% predictive but in combination, that rose to 80%,” Fiehn said. In other words, eight out of ten people with early stage cancer would be correctly identified by the combined test.
If the double biomarker were in use as a clinical test, those patients could then be referred for a low-dose CT scan to confirm the presence of cancer.
These findings were published in the Journal of Clinical Oncology (2015; doi:10.1200/JCO.2015.61.7779).
