Scavenging for protein biomarkers for lethal prostate cancer

It is estimated that approximately 1000 men dies from prostate cancer each year in Norway. This is a relative high number when compared to the 5000 men that are diagnosed with prostate cancer yearly in Norway. Most of these men live a long time after their diagnoses before it starts to progress, and there is a lethal outcome. Because of this long lag time between diagnoses and a lethal event, it is essential to have patient cohorts with long follow up time when the aim is to identify biomarkers that stratifies between indolent and aggressive prostate cancer. An important source for such cohorts is the pathology departments where they have archival tissue material from prostate cancer patients. The tissue is in most cases stored after being formalin fixed and paraffin-embedded (FFPE) to preserve the structure of the tissue samples. An advantage of FFPE tissue is that it can be stored for a long time, and one can use tissue from patients that were diagnosed decades ago, and combine it with follow update from these patients. There are some technical challenges when analyzing FFPE tissue, but new and improved technologies and methods in recent years have made cohorts of FFPE tissue highly relevant in the search for new biomarkers. We have analyzed FFPE tissue using mass spectrometry and the NanoString technology, from patients that have died from prostate cancer within 10 years after diagnosis or were still alive 10 years after they were diagnosed. Presently we are validating promising biomarkers candidates that were identified, by using independent validation cohorts. 

Major Vault Protein (MVP)

We used an explorative cohort consisting of 23 Formalin fixed paraffin embedded (FFPE) tissue samples biopsied from radical prostatectomy samples to run a high-resolution LC-MS/MS analysis (The Proteome core facility -OUH) in an effort to identify protein biomarkers. One of the candidates from this analysis was the Major Vault Protein (MVP), formerly known as Lung resistance protein (LRP). MVP might be involved in drug resistance based on its proposed function in nuclear drug export. MVP is the main component of the vault complex, a ribonuclear protein complex of approximately 13 MDa. It has been reported that MVP expression could be a prognostic and predictive biomarker for different cancer types like lung and bladder. Our analysis, using a validation cohort from the University Hospital of North Norway with tissue samples from 535 prostate cancer patients, showed that high levels of MVP associated with more than four-fold higher risk for death from prostate cancer.

Project member: Håkon Ramberg