Periodic Reporting for period 1 - U-MON (STATISTICAL ANALYSIS AND AI ON PUBLIC CANCER DATA FOR THE DEVELOPMENT OF A HEALTH MONITORING SERVICE)
Período documentado: 2020-12-01 hasta 2022-01-31
To achieve this, we have identified microRNAs as broad-spectrum biomarkers in body fluids that can be measured cost-effectively. MicroRNAs are expressed in organ specific manners and profiling of microRNAs in blood or urine could thus potentially be used to detect organ diseases such as cancer. We defined 2 research goals as objectives for the innovation scheme:
1) To elucidate microRNA panels whose expression levels are associated with specific types of cancer by statictical analysis of public data on RNA expression in tumor tissues.
2) To develop deconvolution algorithms, by using statistical modelling and AI, that can be used to extract the presence of specific cancer types from small RNA expression profiles.
The innovation associate has succesfully completed research aim 1 and had provided a catalog of microRNAs that show tissue and/or tumor specific expression profiles. Algorithms were developed to detect specific cancers from biofluids that can now be tested in the laboratory. The foundation was laid for a multi-cancer deconvolution algorithm, that will be improved with additional data becoming available. We concluded that disease detection and specification on the basis of small RNA profiling is indeed possible and that will further invest in the development of a personalized health monitor.
To understand if the tissue specific microRNA panels could be potentially used as reporters of organ problems, the presence of these microRNAs in plasma samples from healthy individuals was assessed by using sequencing data generated in house at VUMC. Indeed a number of organ specific and organ enriched microRNAs were detected in plasma samples (figure 2). This indicates that indeed using plasma or potentially urine as a source for microRNA profiling, organ diseases could be detected by changes in organ specific microRNA panels.
By comparing tumor tissue microRNA profiles with healthy tissue microRNA profiles it was assessed if changes in microRNA profiles were associated with tumorigenesis that could directly lead to cancer detection. Interestingly indeed several tumor tissues, including breast, colon and prostate showed significant changes in microRNAs, but these were not always changes in tissue specific microRNAs.
Overal the results from this project confirm the observations from literature that tissue specific or enriched microRNA panels exist that are found in body fluids. Moreover, changes of expression in microRNA panels were found associated with specific forms of cancer. The discovered cancer-microRNA panels can be used in separation or combination as algorithms for cancer detection in body fluids and it is likely that this can be extended also to the detection of other organ diseases. The absence of a lung or lung cancer enriched microRNA panel could mean that lung cancer detection by this method will be difficult. In literature however, multiple studies have shown the feasibility of lung cancer detection by microRNA panels in blood, indicating that our current panels may be improved and extended with additional data.
Besides indications for the feasibility of multi-organ cancer detection, the building and curating of 2 large databases of tissue-specific microRNA expression profiles has generated a valuable resource for biomarker discovery and validation.
The results of the project are forming the basis for a scientific manuscript that is currently in preparation and is expected to be ready for submission to a peer reviewed journal in 2022.