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Trinity College Dublin

Creating a Bio-Resource Information System for Prostate Cancer in Ireland

Professor William Watson, UCD Conway Institute of Biomolecular and Biomedical Research
Dr. Darach Golden, TCHPC, Trinity College Dublin.

The Prostate Cancer Research Consortium (PCRC) is a multi-disciplinary, trans-institutional collaboration that is building a shared prostate cancer bio-collection in Dublin city. The High Performance Computing Centre at Trinity College Dublin has been working with the consortium to design one of the first Irish Biobank Information Management Systems (BIMS). The system consists of a central Biobank data repository for the perpetual storage and easy retrieval of anonymous clinical information on patients along with information on their biosamples (tissue, blood, urine).

Both the regulatory and ethical issues surrounding the storage of personal data are incorporated into the design of the BIMS. Although still in its early days, the BIMS has already opened up significant new opportunities for further research and validation for scientists focusing on identifying biomarkers for prostate cancer.

Prostate Cancer
Prostate cancer is a significant cause of illness and death in Irish males. Prostate cancer occurs when cells in the gland multiply out of control due to an accumulation of genetic alterations. In Ireland, prostate cancer is the most common internal cancer in men, representing 11% of all cancers, and 16% of non-skin cancers. There are about 1,700 new cases diagnosed each year and 520 deaths [1]. Although the statistics for this disease are similar to those of female breast cancer, it receives considerably less publicity and health resources.

International comparisons show that the mortality rate of prostate cancer in Ireland is about 15% higher than in the EU, and 30% higher than in the US. The American Cancer Society estimates that during 2008 about 220,000 new cases of prostate cancer will be diagnosed in the United States with an estimated death toll of 27,000.

The Research Imperative
The economic burden of this disease is likely to increase as the male population ages. Many of the costs relating to early stage prostate cancer arise from screening, staging and treatment. The current marker used in screening, prostate specific antigen (PSA), has proved not to be as specific to the disease as first thought in the 1980’s. A significant proportion of current research is focused on identifying new diagnostic and prognostic biomarkers of prostate cancer.

A key requirement of this research is an understanding of the molecular and cellular mechanisms behind the disease. Molecular level information can be obtained from tissue and fluid samples using high throughput genotyping technologies, resulting in 'omic' (genomic, transcriptomic, proteomic, metabolomic) data. Tissue samples can be obtained from patients undergoing biopsy or surgery. Blood and urine samples are usually taken as well. Since genotyping technologies are likely to improve in the coming years, facilities for storage and retrieval of these biosamples for future analysis are very important.

In order to fully evaluate the efficacy of proposed markers, it is necessary to combine the molecular omic data obtained from biosamples with clinical information about the patients who donated the samples. This allows researchers to correlate the efficacy of proposed markers with characteristics of, or disease progression in, subpopulations of patients, and opens up the possibility of personalised medicine.

Prostate Cancer Research Consortium Biobank
PCRC has established a prostate cancer bio-collection in the Mater Misericordiae University Hospital, St James’s Hospital, and Beaumont Hospital. The consortium also includes researchers from Trinity College Dublin’s Institute for Molecular Medicine (IMM), University College Dublin’s Conway Institute and the Royal College of Surgeons, Ireland. It is planned to increase the number of research institutes and hospitals participating in the consortium over time.

Standard Operating Procedures (SOP) for patient consent, sample collection and sample preparation for genomic, transcriptomic and proteomic analysis have been established and validated at all sites, providing uniformity in the resource. The Bio-resource currently has more than 460 tissues with matched serum/plasma samples and over 180 urine samples with comprehensive clinical information and follow up.

Biobank Information Management System
The research requirement for storage of biosamples and of related clinical (and possibly even demographic and lifestyle) data has generated much interest in biobanks or biorepositories [3,4] which store both types of information.

A biobank becomes most valuable when it is embedded in an IT infrastructure which allows researchers to quickly and conveniently perform searches on patient data and to easily discover the physical location of biosamples and obtain information about previous analyses (if any) carried out on them. Such an environment is commonly called a Biobank Information Management System (BIMS) [1].

The PCRC BIMS at the Trinity Centre for High Performance Computing
In 2006, the PCRC received funding from the Health Research Board in Ireland to unify access to their distributed bio-resource with the development of a BIMS. The BIMS system development has been led by the Trinity Centre for High Performance Computing with input from the consortium partners. The system is physically located in Trinity College Dublin.

The BIMS, designed for the PCRC, consists of a central Biobank data repository for the perpetual storage of clinical, pathology, sample information and research omics data. The biosamples themselves remain distributed in the various participating institutions. The system is accessed via a secure, web based front-end with fine grained access control, for the upload, download, storage, query, mining, discovery and sample tracking of data produced by the Prostate Cancer Research Consortium. Data originates from two sources:
Hospital sites: Deidentified clinical, sample and pathology data is uploaded to the BIMS system, via a web browser, by clinical nurses or medical practitioners at the hospital sites.
Research Institutes: Omics data, resulting from analyses of aliquot samples at the research laboratories will be uploaded to the BIMS via a secure web browser (or through secure custom upload modules using an API). Each sample analysis will typically be very large (of the order of gigabytes). Efficient storage and retrieval of such data forms the next stage in the development of the PCRC BIMS

Ethical and Regulatory Requirements
When developing and managing a biobank, it is essential to maintain the trust of donors. If potential donors do not trust the Biobank organisation then they will not provide samples or personal information. Among the measures which are implemented for the PCRC BIMS are Informed Consent: donors are fully informed of the uses to which their biological samples and clinical data will be put and then asked for permission to use their data Deidentification of all data: data stored in the biobank contains no information which reasonably allows identification of patients
Access: Donors are allowed access to their data, and may request that it be removed from the BIMS
Secure environment: restrictions are in place to keep all data safe from unauthorised access.

The PCRC BIMS has successfully undergone a full review by the national Data Protection Commissioner [5]. The Biobank has been registered as a separate entity for the purposes of data protection. It is the one of first Biobanks in Ireland to have undergone this procedure.

Ongoing Research Facilitated by the BIMS
In September 2007, Dr Michelle Downes demonstrated the identification of novel urine markers for the early detection of prostate cancer [6]. This is a significant step forward; indicating urine as a biofluid for the detection of prostate cancer as it drains through the prostate gland carrying proteins directly from the gland. This contrasts with blood which drains many tissues mixed in the central circulation system. It is believed that urine will be a more accurate fluid to detect early signs of disease allowing the use of curative treatment strategies and producing a better long term outcome for the patient.

These novel urinary markers have now been moved to a validation phase using the PCRC Biobank and BIMS. Validation will also be carried out using international data - in collaboration with the International Cancer Biomarker Consortium [7]. This study is being lead by Professor William Watson [6]. The PCRC BIMS will be used to identify cohorts of patients (based on their clinical data) and their urine samples will then be analysed in order to further investigate and validate the proposed biomarkers.

In parallel the BIMS is being used to investigate possible biomarkers for prostate cancer in blood serum. This search is being informed by the urinary markers already found, and may in turn lead to further investigation of possible urinary markers. Once again the clinical data in the BIMS is being used to select groups of patients, whose blood serum will then be subjected to molecular analysis in order to identify biomarkers.

References

  1. http://www.ncri.ie/pubs/pubfiles/summary2007.pdf
  2. BIMS: An information management system for biobanking in the 21st century, G. Olund, P. Lindqvist and J-E.Litton, IBM Systems Journal, 46(1), 2007
  3. Biobanks: Accelerating Molecular Medicine (Challenges Facing the Global Biobanking Community), Z. Zimmerman, M. Swenson and B. Reeve, IDC Special Study 4296, 2004
  4. Biobanks: Collaborating for Cures, I. Melnikova, B. Reeve and M. Swenson, IDC Special Study 4457, 2005
  5. http://www.dataprotection.ie/ViewDoc.asp?fn=/documents/register/display....
  6. http://www.ucd.ie/medicine/research/staff/watson/bio.htm
  7. http://www.fhcrc.org/science/international_biomarker/teams/
  8. https://pcrc.tchpc.tcd.ie/


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