Angiogenic pathological signature and its prognostic power

• Grant number: 14/21360-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 21, 2015
• End date: May 20, 2016
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Carlos Setubal
• Grantee: Rodrigo Guarischi Mattos Amaral de Sousa
• Supervisor: Paul C. Boutros
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Ontario Institute for Cancer Research (OICR), Canada
• Associated to the scholarship: 12/15197-1 - Systems biology of blood vessel formation: a transcriptome study, BP.DR

Abstract

The branching of pre-existing blood vessels to form new ones (angiogenesis) is a physiological process vital to any vertebrate. But this vital process is also involved on the initiation and progress of diseases including cancers, age-related macular degeneration and retinopathies, amongst others. We hypothesized that, while the macroscopic process of remains the same, there are molecular differences between physiological and pathological angiogenesis triggered by the disease microenvironment. We will investigate the existence of a pathological angiogenic signature, exploiting our currently available results and datasets, as well as leveraging large publicly available angiogenesis profiles. We will use computational techniques to define signatures of pathological angiogenesis, and assess the prognostic power of these, as well as their ability to stratify patients with respect to key events in disease development (e.g. tumor development, invasiveness and resistance to therapy). We will evaluate these signatures using large clinical databases from projects such as The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC), which encompass thousands of cancer samples of dozens of tumor types. In particular, we will leverage the ICGC pan-cancer dataset, which is the largest cancer genomic dataset in the world and that is being coordinated through OICR. If validated, our signature can be incorporated into clinical advocating for a treatment based on the molecular profile of the disease and not only in the physical characteristics of the illness, thus enhancing patient survival. (AU)