OPEN Research Support
head

Physician
Anders Frey
Department of Urology, Esbjerg Hospital


Projekt styring
Projekt status    Sampling ongoing
 
Data indsamlingsdatoer
Start 01.04.2018  
Slut 31.07.2021  
 



Investigation of exosomes as circulating and urinary markers of renal cancer

Short summary

The purpose is to prospectively search for and characterize exosomes in blood and urine of patients who underwent biopsy for suspect renal masses in the whole Region of Southern Denmark. We will also investigate the possibility of defining characteristic "exosome signatures" specific for the single different tumor histologies. Comparing molecular determinants obtained from biological fluids and histological preparation are aimed at finding a common circulating marker, that would allow us  to offer patients a "liquid biopsy" of suspicious kidney masses.


Rationale

Renal cell carcinoma (RCC) represents 2-3% of all malignancies, with approximately 84,400 new cases and 34,700 cancer-related deaths in Europe in 2013.

Even though imaging techniques have led to a significant widespread of early diagnosed renal masses, about 50% of them is discovered in clinically locally advanced or even metastatic status, with a subsequent poor prognosis; on the contrary, a significant amount of incidentally diagnosed small renal masses (up to 30% in some case series), are benignant and the patients undergo the risk of an over-treatment. Nowadays, a definitive prove of malignancy can be obtained only from final histology, while renal mass biopsy is still impaired by procedure- and sample-related limitations.

No useful markers to allow a population screening or guide diagnostic strategies have been so far developed.

Recently, a new entity has been identified to be responsible for As a consequence, several circulating biomarkers have been proposed to predict and assess the response to a specific therapy so that we can offer the patients the best possible regimens, as it has recently been summarized by Mijn et al. in their review of the literature.  In particular, identification of circulating nucleic acids, proteins or even cells released from tumors or during treatment with targeted therapies has offered the opportunity to study many aspects related to the tumor itself and its behavior relative to the therapies adopted.

This field of study has already led to important discoveries regarding the mechanisms underlying TKI-resistance.

On the contrary, no circulating markers have been yet identified, in order to state the presence of the tumor, or to define its histological features.

Anyway, the literature in these years has been increasingly reporting the presence of circulating signal molecules, also in localized tumors, that may play a role conditioning the environment surrounding the tumor by modulation of the immune response of the host, or prepare distant organs to receive metastases (forming a "pre-metastatic niche"). These molecules, already investigated in other tumors and less for renal cancer, are transported throughout the body by small membranous vesicles secreted by the cells , called exosomes, that contain, at the same time, also lipids proteins and nucleic acids, whose role seems to be also relevant to the aims of signalling.

Exosomes are often histotype-specific and could also correlate with subsequent aggressiveness determinants and metastatic tendency. 

The aim of our work is to assess the possible presence of molecular tumor biomarkers in biologic fluids (blood and urine). Objects of the study will be a multi center cohort of patients undergoing surgery for suspect renal masses, where we shall look for a shared specific pattern for each histological subtype.

This result would set the basis for a completely non-invasive diagnostic program, that would thus include a "full liquid biopsy" of the kidney mass, avoiding the patients both the risks related to any invasive approach and uncertainties related to the limitations of biopsy sampling.


Description of the cohort

All adult (>18 years old) patients presenting to a Urology department within the Region of Southern Denmark with a suspect contrast enhancing renal mass. No further specific exclusion criteria will be adopted.


Data and biological material

Biological material (blood and urine samples)
Clinical data (clinical history of the patients, previous  diseases, CT-characteristics of the lesions)
Register data (Operatory register data).

Pathology results (both biopsy and final histology).

Results of molecular analysis on the samples.


Collaborating researchers and departments

Department of Urological Surgery, Odense University Hospital

  • Research scholar Alessandro Conti
  • Professor Lars Lund
  • Anja Toft
  • Anja Johansen
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital
  • Søren Feddersen
Departmen of Clinical Pathology 

  • Niels Marcussen
Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region

  • Rodolfo Montironi
  • Giovanni Muzzonigro

NeoGenomics Lab, Irvine, California, USA

  • Maher Albitar