Compartment specific in depth analysis of blood plasma nucleic acids for highly sensitive detection of early metastic events in melanoma disease
- Project Number: LSC15_020
- Project Lead: Jörg Burgstaller, University of Veterinary Medicine Vienna / IFA Tulln (VetMed)
- Project Partner: Karl Landsteiner University of Health Sciences / Division of Dermatology and Venereal Diseases (University Hospital St. Pölten), University of Veterinary Medicine Vienna / Clinical Department of Equine Surgery
- Duration: 48 months starting from 01.05.2017
Biomarkers as indicators for therapeutic mode, onset, and response to treatment are rapidly gaining importance in clinical cancer management. Cancer biomarkers are tumour- or patient-related factors, which reflect the biological behaviour of a tumour and thus constitute a prognostic tool. Cutaneous malignant melanoma is a highly aggressive and metastatic tumour arising from cutaneous pigment cells termed melanocytes. Although incidence of melanoma and related mortality are continuously increasing, it is still impossible to predict the metastatic behaviour of melanoma in individual patients.
In the past five years, the field of "liquid biopsies", i.e. the gain of important information on tumour development via nucleic acid (NA)-based analysis of blood samples, has tremendously progressed. It is now evident that in the blood, tumour-cell derived NAs reside in three different compartments, i.e. (i) intracellular NAs in circulating tumour cells, (ii) NAs in extracellular vesicles, and (iii) freely circulating protein-bound DNA in the plasma. Importantly, extracellular NAs are more abundant in blood, and therefore more accessible.Currently, the clinical applicability of blood-based tumour detection and monitoring methods is still limited to patients with progressive (metastatic) disease. Based on the hypothesis that a compartment-specific NA analysis will considerably aid in improving blood test sensitivity in comparison to holistic approaches, the overall objective of the herein presented study is to exploit the compartmentalization of tumour-derived blood NAs in order to establish a novel strategy for highly sensitive blood-based detection and monitoring of early stage human melanoma disease and metastasis. The applicant and cooperation partners aim at achieving this goal by (i) addressing the amount and composition of extracellular vesicular nucleic acids and circulating free DNA in vitro in order to comparatively evaluate vesicles as a reservoir of potential NA-type biomarkers, (ii) addressing the presence and amount of tumour-derived NA per compartment and possible changes of these parameters over time in a clinical study involving late stage melanoma patients, and by (iii) addressing the presence and amount of the most promising tumour-derived NAs identified in (ii) in a clinical study involving patients with high risk of melanoma recurrence as to achieve earliest possible detection of disease recurrence.