Early detection of cancer increases the patient’s chances of being cured. Research is currently being conducted to detect cancer, identify its type, and follow the effects of treatment by analysing biomarkers in blood, urine and other body fluids. Tumour cells release material into the blood, and one of the goals of the research is to detect cancer using a blood test, independently of the location of the tumour and before the person experiences any symptoms.
The new study has been led by researchers at Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center in the US, and has involved researchers studying small particles released from tumour tissues into the bloodstream. The particles contain proteins, and the cells can use these to communicate with each other within the body – both in healthy persons and in those with disease. The particles are known as “EVPs”, an abbreviation of “extracellular vesicles and particles”.Linda Bojmar is one of the investigators behind the study. Photo credit Children’s Cancer and Blood Foundation
“Our current study identified new protein patterns in EVPs. The proteins can be isolated from EVPs from different tissues and blood. We aim to use them as diagnostic tools to detect cancer at an early stage. We envision a test panel that includes a combination of several of these proteins, in order to maximise diagnostic accuracy”, says Linda Bojmar, postdoctoral fellow at Linköping University and a member of David Lyden’s research group at Weill Cornell Medicine in New York, USA. Linda is one of the principal authors of the article.
In the study, the scientists analysed EVPs from more than 400 samples from blood and tissue, from patients known to have cancer as well as from healthy persons. The study investigated 18 types of cancer, including cancer of the breast, colon, pancreas and lung.
The researchers used “proteomics”, or the large-scale analysis of proteins, to measure and analyse dozens of cancer-related biomarkers in the EVPs. The results were then passed to a machine learning algorithm to sort the information and match specific EVP profiles with various types of cancer. The scientists could in this way use computer analysis to find patterns of proteins in the blood samples that correlated with specific cancer types. Cancer was detected in 95% of cases (the test sensitivity) and the diagnosis was correct in 90% of the cases in which the test had shown the presence of cancer (the test specificity).
The investigators could detect tumours in early stages of cancer such as pancreatic cancer and lung cancer.David Lyden is one of researchers who have led the study. Photo credit Weill Cornell Medicine
“These cancers are rarely detected early, and treating them as soon as possible could result in better patient outcomes”, says Professor David Lyden from Weill Cornell Medicine, who, together with William Jarnagin from Memorial Sloan Kettering in New York, has led the study.
Cancer is a systemic disease in which not only the organ in which the tumour is located is affected, but also other parts of the body. Previous research has shown, for example, that cells of the immune system can form special EVPs when tumour cells are present. Cancer-related EVPs in the blood may therefore come from the tumour cells, from normal cells in the vicinity of the tumour, or from cells in the body far from the tumour, in particular from cells of the immune system. David Lyden’s research group and others have previously shown that cancer cells can secrete EVPs containing proteins that influence other tissues, such that metastatic tumours find it easier to start to grow there. They have called such sites “pre-metastatic niches”.
This means that by examining EVPs that are circulating in the blood, the researchers can gain information from other tissues, in addition to the primary tumour. This may be valuable information in cases in which the disease makes its presence felt through dispersed metastases somewhere in the body, without the location of the primary tumour being apparent. This is the case for approximately 5% of cancer diagnoses. Since the treatments for different types of cancer differ, it may in the future be helpful if the correct diagnosis can be reached through the analysis of EVPs in a blood sample.
The scientists believe that it may also be possible to use cancer-specific EVPs to screen patients with genetic predisposition to cancer and persons with inflammatory diseases that increase the risk of cancer, such as pancreatitis, and the gastrointestinal tract diseases ulcerative colitis and Crohn’s disease. If it turns out that tests of this type can be used in the healthcare system, they may also be useful to follow the effects of cancer treatment.
More research will be necessary before the biomarkers in blood samples can be used to screen for undetected cancer. The researchers plan to continue with studies in larger groups of patients with and without cancer. Linda Bojmar is hoping to start validation trials in Sweden in order to evaluate the results in more detail and investigate outcomes in the Swedish population.
The article: “Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers”, Ayuko Hoshino, Han Sang Kim, Linda Bojmar, Kofi Ennu Gyan, et al., (2020), Cell, published online on 13 August 2020, doi: 10.1016/j.cell.2020.07.009