Soluble Biomarkers in Blood

Introduction

Based on the detection of increased extracellular release and sequestering of latent, active, and inactive forms of prostatic kallikreins (e.g. free and complexed PSA and hK2) this project will generate methods to assess an individual's risk of developing prostate cancer and characterize the nature of the local tumor using early molecular and cellular signatures that result from the transformation of normal prostate epithelium to invasive prostate cancer. Our efforts will address current limitations in both assessing an individual's risk of developing prostate cancer and characterizing the nature of the local tumor and its need for immediate treetment.

Method

We are measuring recently identified novel circulating biomarkers in blood samples from population-based studies. We will use the data generated from optimized pre-analytical and analytical protocols for multiplexed analyses of novel circulating biomarkers (various kallikrein-family gene products and soluble urokinase-receptor forms) in blood to create a prediction tool (nomogram) to help predict the risk of developing clinically significant prostate cancer years before the cancer becomes clinically apparent, with particular focus on the cancer cases most likely to progress, develop metastasis, or die. This tool will be a large improvement on the predictive accuracy of previously established base models including total PSA and digital rectal exams (DREs).

With this project, we hope to address the current lack of reliable guidelines on whom to perform -- or not perform -- systematic prostate biopsies. Theis study is being conducted with 2 international collaborators who performed very large-size population-based studies screening studies where several serial samples were collected over a 10 year of timeframe for each subject.

The following are collaborators from outside Memorial Sloan-Kettering:

• Göran Berglund, MD, PhD, Professor, Department of Internal Medicine, Lund University, University Hospital (UMAS), Malmö, serves as the Principal Investigator of a large population-based observational study cohort that invited all men between the ages of 44 and 50 years and living in the city of Malmö, Sweden.
• Professor Keld Danø, MD, PhD, Chairman, Department of Tumor Biology, Copenhagen University, Finsen Laboratory, Copenhagen, Denmark, and his group of researchers pioneered and identified several of the key components demonstrating the significance of the urokinase system proteins as an important pathway for tumor progression and invasion in various epithelial solid tumor malignancies.
• Hartwig Huland, MD, is Professor and Chairman of the Department of Urology at University Hospital, (UKE), Hamburg Germany. Each year, there are about 1,100 men referred to the Department of Urology at UKE, Hamburg, to undergo detailed biopsy-based clinical and pathologic evaluation. About 500 to 600 men are treated by radical prostatectomy annually.
• Jonas Hugosson, MD, PhD, Professor, Department of Urology, Sahlgrenska University Hospital, Göteborg University, Sweden, serves as the Principal Investigator of the randomized prostate cancer screening study in Göteborg, Sweden, which constitutes the Swedish arm of the European Randomized Study for the detection and treatment of Prostate Cancer (ERSPC, PI: Professor Emeritus Fritz Schröder, MD, Rotterdam, the Netherlands) in which he serves as a Co-Principal Investigator. The Swedish arm of the ERSPC study uses a uniquely designed, biennial protocol to invite 10,000 from randomly selected men who initially were 50 to 66 years of age when the study was started in January 1995.
• Dr. Fritz Schröder (Rotterdam, the Netherlands)