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

Autor: Guarischi-Sousa R; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Monteiro JS; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Alecrim LC; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Michaloski JS; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Cardeal LB; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Ferreira EN; International Research Center (CIPE) A.C. Camargo Cancer Center, São Paulo, SP, Brazil., Carraro DM; International Research Center (CIPE) A.C. Camargo Cancer Center, São Paulo, SP, Brazil., Nunes DN; International Research Center (CIPE) A.C. Camargo Cancer Center, São Paulo, SP, Brazil., Dias-Neto E; International Research Center (CIPE) A.C. Camargo Cancer Center, São Paulo, SP, Brazil.; Laboratory of Neurosciences (LIM27), Institute & Department of Psychiatry, University of São Paulo, São Paulo, Brazil., Reimand J; Computational Biology Program, Ontario Institute for Cancer Research, Toronto, Ontario, Canada.; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Boutros PC; Department of Human Genetics, University of California Los Angeles (UCLA), Los Angeles, CA, United States of America., Setubal JC; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil., Giordano RJ; Biochemistry Department, Institute of Chemistry, University of São Paulo, São Paulo, Brazil.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2019 Dec 17; Vol. 15 (12), pp. e1008482. Date of Electronic Publication: 2019 Dec 17 (Print Publication: 2019).
DOI: 10.1371/journal.pgen.1008482
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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