Prostate cancer is the most commonly diagnosed cancer in men and is among the top five causes of cancer death. In most cases, prostate cancer can be treated successfully, but there is a group of patients who have an aggressive course and often a fatal outcome.
The joint study conducted by a research team led by Robert Wiebringhaus and supervised by Lukas Kenner of the Department of Pathology of MedUni Vienna and the Department of Laboratory Animal Pathology of Vetmeduni, Board Member of the Comprehensive Cancer Center of MedUni Vienna and University Hospital Vienna, has identified new cancer markers in aggressive prostate cancer patients that indicate poorer survival and therefore can be used in the future to help assess risk. The study was published in the highly regarded “Cancers” journal.
In Austria, one in nine deaths among male cancer patients is due to prostate cancer. According to Statistics Austria, around 6,000 men are diagnosed with the disease each year. While some prostate cancers grow slowly and require minimal treatment, there are more aggressive forms that grow very quickly. In order to be able to treat prostate cancer more effectively, it is necessary to understand the complex processes of the tumor at the molecular level.
In 2015, a research team led by experimental pathologist Lukas Kenner of the pathology department of MedUni Vienna and the laboratory animal pathology department of Vetmeduni recognized, using a mouse model, that the STAT3 protein has a surprising tumor suppressor role in prostate cancer. It was shown around this time that patients with low levels of STAT3 in cancer cells experience significantly worse disease progression than patients with high levels. A follow-up study showed that there was a higher metabolic rate in cancerous prostate tissue compared to healthy prostate tissue. This provides the tumor with additional energy to grow and metastasize.
The latest study by doctoral student Robert Wiebringhaus from Lukas Kenner’s team and molecular biologist Brigitte Hantusch is based on these results. For the recent study, the cancerous tissue of the prostate was separated from the healthy tissue using a laser microscope and the proteome, that is, all of the proteins present, was then analyzed by spectrometry. mass (proteomic analysis). This has facilitated the analysis of thousands of different peptides and proteins. It turned out that there was a higher concentration of intracellular mitochondrial respiratory chain proteins in the more aggressive cancer tissue. Mitochondria are organelles, that is, structurally delineated areas of cells with a specific biological function, and are also called “powerhouses of cells”.
In a machinery made up of enzymatic complexes, the so-called respiratory chain or “oxidative phosphorylation” produces energy-rich degradation products via the degradation of sugar and, in a final step, these generate the universal energy vector adenosine triphosphate (ATP) . It is an important regulator of cellular energy production processes. Cells with a particularly high energy requirement, such as cancer cells, can meet this demand through oxidative phosphorylation.
Two proteins of interest from proteomic analysis – NDUFS1 and ATP5O – were further investigated in a collection of patient samples with associated clinical data. Using immunohistochemical staining and data analysis, these two proteins were found to be associated with a lower probability of survival in more aggressive forms of prostate cancer.
Further scans of the transcriptome, which includes all of the genes that are transcribed into the cell at some point in time, also showed a rectified change in the concentration of mRNA (messenger ribonucleic acid). This means that there is a direct correlation between the genetic transcripts and the proteins produced. The current study by Wiebringhaus et al. represents an important step in establishing a link between NDUFS, ATP5O and cancer aggressiveness. NDUFS1 and ATP5O could therefore serve as additional immunohistochemical markers for aggressive prostate tumors and, at the same time, new targets for cancer treatment.
Vienna Medical University
Wiebringhaus, R., et al. (2012) Proteomic Analysis Identifies NDUFS1 and ATP5O as New Markers for Survival Outcomes in Prostate Cancer. Cancers. doi.org/10.3390/cancers13236036.