The topology of vitronectin: A complementary feature for neuroblastoma risk classification based on computer-aided detection

Autores de INCLIVA

• Rebeca Burgos Panadero

  Autor

• 

  Samuel Navarro Fos

  Autor

• 

  Rosa Noguera Salva

  Autor

Participantes ajenos a INCLIVA

• Vicente-Munuera, P
• Noguera, I
• Escudero, LM

Grupos y Plataformas de I+D+i

• Grupo de Investigación Translacional de Tumores Sólidos Pediátricos

  

  Leading Researcher

  Samuel Navarro Fos

Abstract

Tumors are complex networks of constantly interacting elements: tumor cells, stromal cells, immune and stem cells, blood/lympathic vessels, nerve fibers and extracellular matrix components. These elements can influence their microenvironment through mechanical and physical signals to promote tumor cell growth. To get a better understanding of tumor biology, cooperation between multidisciplinary fields is needed. Diverse mathematic computations and algorithms have been designed to find prognostic targets and enhance diagnostic assessment. In this work, we use computational digital tools to study the topology of vitronectin, a glycoprotein of the extracellular matrix. Vitronectin is linked to angiogenesis and migration, two processes closely related to tumor cell spread. Here, we investigate whether the distribution of this molecule in the tumor stroma may confer mechanical properties affecting neuroblastoma aggressiveness. Combining image analysis and graph theory, we analyze different topological features that capture the organizational cues of vitronectin in histopathological images taken from human samples. We find that the Euler number and the branching of territorial vitronectin, two topological features, could allow for a more precise pretreatment risk stratification to guide treatment strategies in neuroblastoma patients. A large amount of recently synthesized VN would create migration tracks, pinpointed by both topological features, for malignant neuroblasts, so that dramatic change in the extracellular matrix would increase tumor aggressiveness and worsen patient outcomes.

© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC

Keywords

• neuroblastoma; vitronectin; topology; computational biology; networks