A Study in Cell Identifies a 14-Protein Signature in Blood
A new study published in the journal Cell reports the identification of a 14-protein signature in blood that may predict an individual's risk of developing lung cancer more than five years before diagnosis.
The research was conducted by scientists at the Francis Crick Institute and University College London, with funding from Cancer Research UK and the European Research Council.
Methodology and Key Findings
Researchers applied machine learning to analyze blood plasma protein data from over 48,000 UK Biobank participants, cross-referencing the data with cancer registry records. The analysis identified 14 proteins associated with a future lung cancer diagnosis within five years.
The protein signature was subsequently validated in eight datasets from international cohorts, including a group of individuals who had never smoked.
Analysis suggested that the signature does not originate from the tumor itself but reflects an altered inflammatory environment in the lungs that precedes the development of cancer.
The signature was also found to be elevated in individuals who later developed idiopathic pulmonary fibrosis or chronic obstructive pulmonary disease (COPD).
Biological Mechanism
Previous research indicated that air pollution can trigger immune cells in the lung to release a signaling molecule called interleukin-1 beta (IL-1β), which in turn activates dormant cells carrying cancer-causing mutations.
In this study, exposure to pollution in laboratory settings was observed to increase the protein signature and expand a cell population known as KAC cells, which can become cancerous. Blocking IL-1β in mice was shown to reduce the number of KAC cells and slow early tumor development.
Clinical Implications
A re-analysis of data from the CANTOS trial, which tested the IL-1β blocker canakinumab for cardiovascular disease, showed that participants with a high baseline level of the 14-protein signature experienced a nearly 50% reduction in lung cancer incidence when receiving canakinumab.
According to the researchers, the number needed to treat with the drug to prevent one case of lung cancer in this high-risk group was 55, a figure they noted as comparable to the number needed to treat with statin therapy for cardiovascular prevention.
Statements from Researchers
Tej Pandya, a Clinical PhD Student at University College London and the Francis Crick Institute, described the finding as "a proof of concept that, one day, we could use this signature to offer preventive treatment to people at risk of lung cancer."
Charlie Swanton, a researcher at the Francis Crick Institute and University College London, stated that the work supports the concept of "a common, presymptomatic inflammatory state underlying age-related diseases" and provides insight into "this window of opportunity, when preventative treatment could work best."
Hayley Brown, of Cancer Research UK, said the research "brings us closer to intervening sooner and potentially stopping the disease before it starts."