Circulating Cell Scoring System Identifies High Risk Prostate Cancer Interview with:

Dr. Yong-Jie Lu Reader in Medical Oncology Centre for Molecular Oncology Barts Cancer Institute - a CR-UK Centre of Excellence Queen Mary University of London John Vane Science Centre, Charterhouse Square, LONDON

Dr. Yong-Jie Lu

Dr. Yong-Jie Lu MBBS, MD, PhD
Reader in Medical Oncology
Centre for Molecular Oncology
Barts Cancer Institute – a CR-UK Centre of Excellence
Queen Mary University of London
John Vane Science Centre, Charterhouse Square
London What is the background for this study?

Response: Identifying/monitoring the occurrence of metastasis and the prediction of the length that a patient may survive with a prostate cancer is critical for doctors to select the proper treatment, aiming to achieve the best control of the cancer with a balance of quality of life. Currently this is achieved mainly by analysing the cancer tissues acquired through very invasive procedures or by expensive imaging techniques, most of which expose the patient to toxic radioactive materials.

Circulating tumour cells (CTCs), which play a key role in the metastasis process, have been shown for their potential to be used for cancer prognosis by a simple blood sample analysis. However, previous CTC studies mainly detect the epithelial type of CTCs. Using the ParsortixTM (ANGLE plc) cell-size and deformability based CTC isolation system, we analysed not only epithelial CTCs, but also CTCs with epithelial-mesenchymal transition (EMT), a cellular process associated with cancer invasion and metastasis. What are the main findings?

Response: We found that the number of EMTing CTCs (in the process of EMT) was closely correlated with whether the patient’s cancer had become metastatic and the number of EMTed CTCs (completed EMT), which cannot be captured by many CTC isolation systems, was associated with poor patient survival.

We also discovered another type of rare cells in the blood, known as ‘megakaryocytes’ – large bone marrow cells which produce platelets for blood clotting. Megakaryocytes in patient blood have never before been linked to cancer prognosis, but we found that patients with greater numbers of megakaryocytes survived much longer.

We showed that combining the number of EMTing CTCs with the patient’s PSA level has the potential to predict metastasis at 92 per cent accuracy. A combined EMTed CTC and megakaryocyte scoring system was developed based on data from 40 patients studied over a 20 month period. A score above 2 identified patients, who were 10 times more likely to die from their disease in the short term than those with a score below 2. What should readers take away from your report?

Response: It is critical to detect all types of Circulating tumour cells for cancer diagnosis, prognosis and progression monitoring. The potential of megakaryocyte analysis in cancer prognosis should be fully explored. What recommendations do you have for future research as a result of this study?

Response: Large cohort study, in particular in the form of clinical trial should be performed to validate the findings in prostate cancer, which will support its clinical implementation. This circulating cell analysis approach should be applied to other cancers for biomarker development. Is there anything else you would like to add?

Response: Because of its ability to capture all types of Circulating tumour cells and the megakaryocyte cells, not previously known to be associated with cancer survival, the Parsortix, cell size and deformability based CTC isolation system, shows potential for much improved cancer diagnosis, prognosis and progression monitoring. Any disclosures?

Response: The study was partially supported by ANGLE plc, but the company had no influence of the study design, conduction and data analysis.


The novel association of circulating tumor cells and circulating megakaryocytes with prostate cancer prognosis

Lei Xu, Xueying Mao, Tianyu Guo, Pui Ying Chan, Greg Shaw, John Hines, Elzbieta Stankiewicz, Yuqin Wang, R. Tim D. Oliver, Amar Sabri Ahmad, Daniel Berney, Jonathan Shamash and Yong-Jie Lu