Researchers have developed a sensitive blood test for a highly specific biomarker of multiple common tumors, laying the groundwork for a product that could improve cancer screening.
The research, details of which were published in Cancer Discovery, is focused on LINE-1-ORF1p, a protein that is encoded by a viruslike element present in every human cell. Such elements, which are called transposons, are expressed in sperms and eggs and during embryogenesis but are then silenced because their activity stresses cells. The transposon that encodes LINE-1-ORF1p is reactivated in cancer cells.
Because production of LINE-1-ORF1p is suppressed by healthy cells but not cancers, the presence of the protein is a potential biomarker for the presence of a tumor. An international team of researchers used that fact to develop a sensitive, specific, and affordable cancer-screening test.
The resulting ultrasensitive digital immunoassays detected low levels of the protein in plasma across multiple cancers with high specificity. Further assessment of the test, which costs less than $3 to make, determined that it has promise in screening ovarian cancer. At 98% specificity, the test showed that 71% of ovarian cancers were LINE-1-ORF1p positive. The protein was detectable in some early-stage patients.
In a statement, John LaCava, PhD, a research associate professor at The Rockefeller University and a co-author on the paper, discussed how the test could enable screening for multiple cancers by healthcare systems.
“During a healthy time in your life, you could have your ORF1p levels measured to establish a baseline. Then your doctor would just keep an eye out for any spikes in ORF1p levels, which could be indicative of a change in your state of health. While there might be some minor ORF1p fluctuations here and there, a spike would be a cause for a deeper investigation,” LaCava said.
The collaborators also assessed the potential to use the test for early therapeutic response monitoring in gastroesophageal cancers. In a study of 19 gastroesophageal cancer patients, levels of LINE-1-ORF1p fell to below the detectable limit in the 13 people who responded to treatment.
While the results are promising, more work needs to be done on the test. The researchers named validatory studies in larger cohorts and assessments of the normal baseline level of circulating LINE-1-ORF1p as areas of ongoing activity.
