A blood test analyzing a signature of 14 proteins can identify individuals at elevated risk of a lung cancer diagnosis within five years, according to a new study published in Cell.
The Discovery
A study published in the journal Cell has identified a signature of 14 proteins in human blood that is associated with an elevated risk of receiving a lung cancer diagnosis within five years. The research, conducted by scientists at the Francis Crick Institute, University College London, and the Walter and Eliza Hall Institute of Medical Research (WEHI) in Australia, analyzed data from over 48,000 participants and validated the findings across eight international datasets, including a cohort of individuals who had never smoked.
Methodology and Findings
The research team used a machine learning algorithm to analyze blood plasma protein data and cancer registry records from participants in the UK Biobank. The algorithm combined the levels of 14 specific proteins with other variables, including the participant's age, smoking status, and history of lung disease. The resulting 14-protein signature was then validated in eight independent datasets from populations around the world.
Biological Origin of the Protein Signature
Analysis indicated that the 14-protein signature is not derived from a tumor itself. Instead, the researchers concluded that the signature reflects an altered, pre-existing inflammatory state in the lung environment. This signature was also found to be elevated in individuals who later developed chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis.
Proposed Mechanism
The research builds on previous work regarding the role of inflammation in cancer development. Prior studies had indicated that air pollution can trigger immune cells in the lung to release a protein called interleukin-1 beta (IL-1β), which can activate dormant cells with cancer-causing mutations. In this study, experiments on mice showed that exposure to pollution increased the protein signature and expanded a population of cells known as KAC cells, which can become cancerous. Blocking IL-1β in these mice was reported to reduce the number of KAC cells and slow early tumor development.
Clinical Implications and Potential Applications
Researchers re-analyzed data from the CANTOS trial, a clinical study that tested the IL-1β blocker canakinumab for cardiovascular disease. The re-analysis indicated that participants in the trial who had a high baseline 14-protein signature experienced approximately a 50% reduction in lung cancer incidence when treated with canakinumab. The researchers calculated that, within the high-signature group, treating 55 individuals would prevent one case of lung cancer.
The study suggests the 14-protein signature could potentially be used to identify individuals at high risk for lung cancer who might benefit from preventive treatments. Current screening programs for lung cancer are generally limited to older individuals with a history of heavy smoking. The researchers noted that the signature was validated in non-smokers, indicating a potential application for screening individuals exposed to other risk factors, such as air pollution.