| Zusammenfassung |
Lung cancer is one of the most common cancers in the UK, killing around 35,000 people each year. Around 40% of lung cancer patients will develop a malignant pleural effusion (MPE), a collection of fluid which builds up between the lung and the chest wall. The volume of this fluid can be great enough to compress the lung, causing breathlessness. Some patients experience MPE very differently to others. For example, some will survive much longer or will produce fluid much more quickly. These variations between people makes predicting what will happen and choosing the best treatments extremely challenging. Most treatments for MPE rely on invasive procedures to drain the fluid, which often cause a major impact on a patient's remaining quality of life. At present, we have no reliable blood or pleural fluid tests which can help determine how best to manage patients with MPE or which might give a better idea of what will happen to them. Each person's individual DNA pattern (their genome) underpins how their body functions. Over time, or in response to certain exposures or diseases, DNA can accumulate chemical alterations which affect how its genetic information is interpreted. The study of this phenomenon is called epigenetics, with a key alteration being 'DNA methylation' (DNAm). Levels of DNAm have been found to be associated with the development of a wide range of cancers, including lung cancer. DNAm analysis techniques are improving rapidly, allowing more of the genome to be tested than in the past. DNAm testing can be applied to pleural fluid, although past research has usually focused on whether cancer is present or not rather than predicting what will happen to a person who already has cancer. The aim of this project is to assess whether the levels of DNAm in the pleural fluid of a person with lung cancer can be used to forecast what will happen to them. Primarily, we will check whether it can predict how long a patient is likely to survive, but we are also interested in whether it can provide knowledge about whether treatments will work or not and whether the different behaviours of MPE can be predicted before they happen. To do this, we will ask 100 patients with MPE due to lung cancer from Bristol and Glasgow to join an observational study for 6 months. During the study, we will collect pleural fluid and blood samples alongside comprehensive information about what is happening to each person's disease (for example with CT scans) and how they are responding to the treatments they are given, both for the cancer and the fluid. Most importantly, we will track who survives and who does not during the study. We will then apply the latest laboratory and computational techniques to some of the fluid samples we have collected, to see whether the levels of DNAm correlate with what happens to the patients in the study. Benefits from this project are expected to be: 1) The gathering of high-quality information which will allow us to design further, conclusive studies to test whether pleural fluid DNAm levels can help to predict what happens to lung cancer patients with MPE. Ultimately, we hope to create a new, accessible, DNAm-based test which can be applied to samples of pleural fluid obtained from patients in outpatient clinics. This test could be used routinely by NHS doctors to predict the likely outcome of a person's MPE, helping patients better understand their disease and informing conversations about how best to manage it in their case. 2) The collection and storage of patients' clinical information and samples with a mind to further testing, which will allow us (and future cancer researchers) to apply more of the most up-to-date scientific techniques to predict how a person's MPE will behave over time. 3) A better understanding of how and why lung cancer and MPE develops and progresses, with the potential to reveal new targets for novel drug therapies and to open up new avenues for MPE research. |
