The use of HRMAS for tissue metabolomics - A case study

Efforts to unravel molecular information about prostate cancer subtypes is critical for diagnostics and treatment of prostate cancer. In this multidisciplinary study, led by Prof. Pernilla Wikström and Prof. Anders Berg at the Department of Medical Biosciences at Umeå University, high resolution magic-angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy was used together with advanced chemometric tools to obtain metabolic profiles of intact prostate tissue samples. The NMR experiments and subsequent data analysis were performed by Dr. Ilona Dudka at the Swedish NMR Centre at Umeå Univsersity.

This non-destructive NMR technique enables subsequent analysis of the sample (histopathological evaluation, gene expression profiling, immunohistochemistry) as it causes minimal tissue architectural disruption.

This study builds on prior studies to unravel molecular information of prostate cancer subtypes performed by the same group. Previously, based on transcriptomic data, they identified three clinically relevant subtypes of PC bone metastases: MetA, MetB and MetC, of which MetB shows a particularly aggressive behavior.

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Ilona Dudka loading HRMAS rotors with tissue samples into the sample changer connected to the 500 MHz NMR instrument at the Swedish NMR Centre, Umeå University.

This approach allowed not only separation of benign prostate samples from prostate tumors, but also discrimination of PC aggressiveness based on tumor cell differentiation, by separating ISUP grade group 2 from ISUP grade group 3. Most importantly, they could also reveal for the first time significant differences in the metabolic phenotypes for previously established prostate cancer subtypes differentiated based on Ki67/PSA immunoreactivity. Their study creates a possibility for precision medicine and tailor-made treatment of patients based on the specific biology of prostate cancer subtypes.