Project: A GLYcomic approach for the diagnosis of PROstate cancer

Prostate Cancer is the most common cancer in males and the second leading cause of male cancer-related death in the Western world. Each year, over 500.000 males are diagnosed with prostate cancer. The disease is associated with high morbidity and has a high impact on the quality of life of patients. Prostate cancer may cause pain, difficulty in urinating and erectile dysfunction but often is asymptomatic. Current detection methods for prostate cancer do not provide accurate diagnosis._x000D__x000D_A major problem with undiagnosed or late diagnosis of prostate cancer is the development of metastases to bone tissue. The only currently available method to confirm diagnosis of prostate cancer is an invasive biopsy. Unfortunately, currently available non-invasive tools for the detection of prostate cancer have limitations in sensitivity, specificity and speed. Prostate Specific Antigen (PSA) serum screening is the most widely used test. This relies on the detected level of PSA in serum which is hypothesized to be elevated in the presence of prostate cancer. _x000D__x000D_The method to detect PSA is very sensitive but not cancer-specific and this has led to substantial controversy around the PSA test. Serum PSA levels can also be increased as a result of other conditions (e.g. benign prostatic hypertrophy and prostatitis). Due to insufficient correlation of PSA with the presence of cancer, PSA tests show very high rates of false-positive results. Only about 30% of men with increased PSA levels have a positive biopsy. Of greater concern, 20–30% of men with prostate cancer have serum PSA levels in the normal range, resulting in undiagnosed disease. Therefore it is important to develop a fast, simple, specific and reliable test. Ideally, such a test should be non-invasive and able to confirm the presence of prostate._x000D__x000D_The present program aims to develop a novel diagnostic method for the early detection of prostate cancer based on novel discoveries in the field of glycobiology, in which the consortium has a world-leading role. Glycobiology focuses on the glycosylation process where specific glycan (sugar) structures are attached to proteins, lipids and other molecules expressed by cells. For decades it has been known that cancer is associated with specific aberrant glycosylation on molecules secreted or expressed by cancer cells. Later studies show that these glycan structures are not random, but correlate to specific malign states of cancer. High expression of some glycan epitopes is associated with poor prognosis, invasions and metastasis of tumors. It has also been shown that these specific glycan structures influence the immune system through LECTIN RECEPTORS on immune cells in such way that this allows cancer to progress to metastatic stage. Several academic groups have reported that these specific glycan structures are also present on PSA derived from normal prostate cells and from prostate cancer cells (1,2). The ability to differentiate between glycan structures on PSA from cancerous and healthy origins would make these glycan structures ideal biomarkers for the development of novel diagnostic tools. Unfortunately this area of study has received little attention since the structural and functional concepts of glycosylation in cancer and immunology are difficult to investigate and results from current techniques relying on PLANT-DERIVED LECTIN RECPETORS are difficult to translate to the human situation._x000D__x000D_DC4U and the VU University Medical Center (VUMC) have recently developed unique screening probes for the identification of glycan changes in tumor-associated antigens (TAA). Unique about these probes is that they were developed using HUMAN LECTIN RECEPTORS on antigen presenting cells. These probes allow the study of the interaction of specific glycan structures on proteins originating from HUMAN TUMOR CELLS, expressed in serum and secretion fluids. The assay system and the probes developed by DC4U and VUMC are very robust . DC4U and the VUMC have used this technology to discover glycan structures in breast and colon cancer. These glycan changes show a strong comparison with glycan changes reports on PSA with respect to the different cancer stages (3). _x000D__x000D_With this project, the consortium aims to develop a novel assay to detect tumor specific glycan structures on PSA in blood or urine to facilitate prostate cancer diagnosis. This technology would enable TRUE DIAGNOSIS of prostate cancer, based on the differentiation between PSA from non-cancerous and cancerous origin in different stages, taking away current uncertainty in diagnosis and prognosis. The consortium aims to provide proof of principle for the detection method and validate the prototype assay in a clinical study._x000D_For this effort, DC4U, VUMC, Erasmus Medical Center, the University of Turku and Procognia Ltd will join forces. The individual Ps bring their own unique and complementary expertise in immune-biology, clinical oncology, glycobiology and assay development.

Acronym	GLYCOPRO (Reference Number: 4813)
Duration	01/07/2009 - 31/12/2012
Project Topic	With this project, the consortium aims to develop a novel assay for tumor specific glycan structures on PSA in blood or urine to facilitate prostate cancer diagnosis.
Project Results (after finalisation)	We have shown that it is possible to set up an assay which recognizes specifically glycans on prostate-specific antigen (PSA) molecules combining PSA specific antibodies and lectins of plant or human origin. In addition, we got promising results with urine samples from males with and without prostate cancer. The most promising assay concept might be able to enhance the discrimination between men with benign condition and men with prostate cancer.
Network	Eurostars
Call	Eurostars Cut-Off 2

Project partner

Number	Name	Role	Country
5	DC4U B.V.	Coordinator	Netherlands
5	Erasmus Medical Center	Partner	Netherlands
5	Procognia Limited	Partner	Israel
5	University of Turku	Partner	Finland
5	VU University Medical Center	Partner	Netherlands