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'Tissue is the issue': a multi-omics approach to improve prostate cancer diagnosis

Periodic Reporting for period 4 - ProstOmics ('Tissue is the issue': a multi-omics approach to improve prostate cancer diagnosis)

Reporting period: 2022-08-01 to 2023-07-31

Due to an aging population, it is expected that significantly more men will be tested for elevated serum prostatic specific antigen (PSA) and diagnosed with prostate cancer in the coming decade. Currently available diagnostic methods cannot efficiently differentiate between the aggressive and the slow-growing types of prostate cancer. This leads to over-diagnosis of many clinically insignificant cases which may again cause adverse treatment effects such as impotence and incontinence, reduced quality of life and a heavy financial burden on worldwide health care systems. The need for good clinical diagnostic and prognostic biomarkers is therefore urgent to prevent over-diagnosis, but at the same time detect cases of rapid-growing life-threatening prostate cancer. The focus of ProstOmics is to combine novel and established “omics” methodologies to obtain unconventional data material which may provide novel biomarkers and new progress in understanding molecular mechanisms within prostate cancer diagnosis and prognosis.
ProstOmics has led to the development of a unique multi-omics protocol which is currently being performed for the first time. A detailed protocol paper will soon be published. Several protocol developments have been performed to optimize the different omics analyses especially considering tissue processing, storage and transportation which will be published consecutively. ProstOmics has also led to a novel discovery when the metal zinc (in the form of zinc trichloride) was detected by metabolite-targeted MALDI-imaging, and provided the possibility for simultaneously detecting the spatial distribution of prostate-specific compounds zinc and its metabolites citrate and aspartate in a single MALDI analysis (Andersen et al, Analytical Chemistry 2020, see figure). This will be a valuable tool in the large-scale analyses to investigate their biomarker role in diagnosis and prognosis.
The ERC funding has led to new opportunities to implement novel tissue technology such as spatial transcriptomics, spatial proteomics (MALDI Imaging) and DNA methylation analysis into the multi-omics protocol. This has gone beyond the state-of-the-art and beyond the original plan of the ProstOmics project. We expect that the multi-layer omics data will produce valuable insights and understanding of prostate cancer which may be important for improving diagnosis and prognoses, and possibly save patients from over-diagnosis and society from financial burdens.
Spatial distribution of zinc was detected by metabolite-targeted MALDI MSI