Researchers Identify Possible Biomarker for Early-Stage Lung CancerA protein that can be detected in blood samples may one day serve as a biomarker for early-stage lung cancer, according to new study results. The findings, published October 16 in the Proceedings of the National Academy of Sciences, suggest that measuring the levels of a variant form of the protein Ciz1 may help detect lung cancer early and noninvasively in high-risk individuals.
“We have struggled to find cancer biomarkers that are disease-specific, and this may be a step in the right direction,” said Dr. Sudhir Srivastava, chief of NCI’s Cancer Biomarkers Research Group. He called the study “promising” but noted that the results will need further validation.
Researchers led by Dr. Dawn Coverley of the University of York in the United Kingdom found that the “b-variant” form of Ciz1 was present in 34 of 35 lung tumors but not in adjacent tissue. Additional experiments showed that an antibody specific for this Ciz1 variant could detect the protein in small samples of blood from individuals with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).
In two independent sets of blood samples—from 170 and 160 patients, respectively—the researchers showed that variant Ciz1 levels above a certain threshold correctly identified 95 to 98 percent of lung cancer patients, with an overall specificity of 71 to 75 percent. Using the second set of samples, they showed that the level of variant Ciz1 could discriminate between patients with stage I NSCLC and age-matched heavy smokers without diagnosed cancer, individuals with benign lung nodules, and patients with inflammatory lung disease.
Although the high rate of false-positive test results seen with variant Ciz1 is a concern, the authors noted that a blood test for the Ciz1 variant might ultimately be shown to be useful when combined with low-dose helical computed tomography, also called spiral CT, for lung cancer screening. In that context, the test could confirm the presence of lung cancer in patients who have suspicious spiral CT results, reducing the need for invasive procedures to confirm a lung cancer diagnosis. And, if used before spiral CT, “the test could reduce the number of people who undergo imaging…[because] the false-negative rate is very low,” Dr. Coverley wrote in an e-mail message.
To assess variant Ciz1 levels, the researchers used a laboratory method known as Western blot analysis. However, this approach could not be routinely applied in a clinical context, the researchers acknowledged, so “a more streamlined method” for testing would need to be developed.
Supported in part by NCI Early Detection Research Network Grant U01CA086137.