A transcriptome-based signature of pathological angiogenesis predicts breast cancer patient survival


Autoři: Rodrigo Guarischi-Sousa aff001;  Jhonatas S. Monteiro aff001;  Lilian C. Alecrim aff001;  Jussara S. Michaloski aff001;  Laura B. Cardeal aff001;  Elisa N. Ferreira aff003;  Dirce M. Carraro aff003;  Diana N. Nunes aff003;  Emmanuel Dias-Neto aff003;  Jüri Reimand aff002;  Paul C. Boutros aff006;  João C. Setubal aff001;  Ricardo J. Giordano aff001
Působiště autorů: Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil aff001;  Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada aff002;  International Research Center (CIPE) A.C. Camargo Cancer Center, São Paulo, SP, Brazil aff003;  Laboratory of Neurosciences (LIM27), Institute & Department of Psychiatry, University of São Paulo, São Paulo, Brazil aff004;  Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada aff005;  Department of Human Genetics, University of California Los Angeles (UCLA), Los Angeles, CA, United States of America aff006
Vyšlo v časopise: A transcriptome-based signature of pathological angiogenesis predicts breast cancer patient survival. PLoS Genet 15(12): e32767. doi:10.1371/journal.pgen.1008482
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008482

Souhrn

The specific genes and molecules that drive physiological angiogenesis differ from those involved in pathological angiogenesis, suggesting distinct mechanisms for these seemingly related processes. Unveiling genes and pathways preferentially associated with pathologic angiogenesis is key to understanding its mechanisms, thereby facilitating development of novel approaches to managing angiogenesis-dependent diseases. To better understand these different processes, we elucidated the transcriptome of the mouse retina in the well-accepted oxygen-induced retinopathy (OIR) model of pathological angiogenesis. We identified 153 genes changed between normal and OIR retinas, which represent a molecular signature relevant to other angiogenesis-dependent processes such as cancer. These genes robustly predict the survival of breast cancer patients, which was validated in an independent 1,000-patient test cohort (40% difference in 15-year survival; p = 2.56 x 10−21). These results suggest that the OIR model reveals key genes involved in pathological angiogenesis, and these may find important applications in stratifying tumors for treatment intensification or for angiogenesis-targeted therapies.

Klíčová slova:

Angiogenesis – Breast cancer – Gene expression – Medical hypoxia – Retina – RNA sequencing – Transcriptome analysis – Oxygen-induced retinopathy


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Genetika Reprodukční medicína

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PLOS Genetics


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