PROLIPSY

Early detection of prostate cancer by liquid biopsies

Consortium Project abstract Final Summary

Project Coordinator

Klaus PANTEL
- University Medical Centre Hamburg Eppendorf
- Hamburg - Germany

Project Partners

Desiree BONCI
- Istituto Superiore di Sanità
- Rome - Italy
Catherine ALIX-PANABIÈRES
- University Medical Centre
- Montpellier - France
Evi LIANIDOU
- University of Athens
- Athens - Greece
Maciej ZABEL
- Poznan University of Medical Sciences
- Poznan - Poland

Prostate cancer (PCa) is a major cause of cancer-related mortality and morbidity in men of the western world. Standard PSA screening has a high rate of false-positive findings (up to 60%) and therefore more specific methods for early detection of PCa are urgently needed. Recently, partners of our consortium have played a key role in implementing the concept of “Liquid biopsies” (i.e., analysis of tumour cells or tumour cell-derived nucleic acids and exosomes in blood) into research on PCa (TRANSCAN project CTC-SCAN, ended in 2016) and other solid tumours (EU/IMI project CANCER-ID). The primary aim of this research proposal is to improve blood-based detection of PCa patients by testing of circulating tumor cells (CTCs), tumour-derived exosomes and circulating cell-free DNA (cfDNA) as Liquid biopsies.
Analysing peripheral blood samples from men with elevated PSA concentrations that undergo prostate biopsy, we will stratify patients in cancer and non-cancer cohorts based on the outcome of the histological evaluation of the tissue biopsy. Cancer patients will undergo surgical resection or radiotherapy. In the first year (discovery period), we will assess which Liquid biopsy marker or combination of markers will (i) provide the best discrimination between the two cohorts and (ii) identifies in particular high-risk PCa patients with aggressive tumour as defined by a Gleason score (“gold standard”) of 8 or higher. Biobanks from former studies on PCa (e.g., CTC-SCAN) will be used in particular for plasma studies (cfDNA, exosomes).
Candidates will be further explored in the subsequent training and validation study (years 2 and 3) in order to obtain the blood test with the highest sensitivity and specificity for detection of early PCa and/or high-risk PCa. Blood from men with elevated PSA levels (gold standard for PCa screening) will be analysed prospectively before tissue biopsy are taken to avoid biopsy-induced interference of blood results. Comparing the results of Liquid biopsy with tissue biopsy histology (gold standard for PCa diagnosis) we will identify single or bloodbased marker combination with the highest sensitivity and specificity for detection of total PCa and/or high-risk PCa. The unique combination of expertise assembled in this consortium will guarantee a complementary investigation of the relevance of Liquid biopsy for early detection of PCa at the European level.

The primary aim of the PROLIPSY study is to improve blood-based detection of prostate cancer patients by testing of circulating tumour cells, tumour-derived exosomes and circulating cell-free DNA as new blood-based biomarkers. The PROLIPSY study has been divided into a discovery and a validation phase. The scientific work has been divided into seven work packages, which encompasses the recruitment of test persons, the validation of individual technologies and the statistical assessment of test results.
During the validation phase we have successfully built up logistics for patient recruitment and sample processing protocols and validated four of the five proposed liquid biopsy assays to prove their usability for early prostate cancer detection. We have been able to validate protocols for CTC isolation and enumeration by Cyto-Track and CTCapture assays. Protocols for tumour-DNA and exosome isolation from blood plasma have also been established. Analysis of a retrospective patient cohort of 120 patients revealed 37 differentially expressed antigens and 4573 possible miRNAs as possible candidate biomarker for early PCa detection. The three methods for determining the number of CTCs, which were tested by individual consortium member, have not achieved the required sensitivity for a robust CTC detection in early prostate cancer patients by end of the discovery phase. However, these technologies have been continuously optimized during the reported period. Especially the EPIDROP Chip has constantly been optimised during the course of the PROLIPSY study. By end of the discovery phase, the blood plasma-based biomarkers, i.e. the methylation patterns in circulating tumour DNA, have been chosen to be validated on larger patient groups.
The scientific work during the validation phase has significantly been hindered by the restrictions caused by the COVID19-pandemic, which slowed down both the experimental work as well as patient recruitment. As consequence, the consortium has not been able to complete the whole project plan of PROLIPSY study within the initially proposed time frame. Despite the diverse difficulties caused by the COVID19 pandemic, we have been able to continuously enrol patients. By end of the study, we have been able to recruit a total of 1023 test persons. By implementing additional genome-wide sequencing approaches of both circulating tumour DNA and mRNA-load of exosomes, which have not been part of the initial project plan, we have been able establish additional blood-based biomarker candidates for early prostate cancer detection. By end of the funding period, we have not been able to complete validation of the identified cfDNA-, miRNA- or mRNA-biomarkers in the entire study cohort and the final statistical assessment of individual or combined biomarkers for early prostate cancer detection is pending.

Subscribe to our Newsletter
You can unsubscribe at any moment by clicking on the subscription preferences link at the bottom of a received newsletter.

This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 964264.

Legal Notice | Privacy Policy