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

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A transcriptome-based signature of pathological angiogenesis predicts breast cancer patient survival.
PLOS Genetics ( IF 4.0 ) Pub Date : 2019-12-17 , DOI: 10.1371/journal.pgen.1008482
Rodrigo Guarischi-Sousa _{1,

2} , Jhonatas S Monteiro ₁ , Lilian C Alecrim ₁ , Jussara S Michaloski ₁ , Laura B Cardeal ₁ , Elisa N Ferreira ₃ , Dirce M Carraro ₃ , Diana N Nunes ₃ , Emmanuel Dias-Neto _{3,

4} , Jüri Reimand _{2,

5} , Paul C Boutros ₆ , João C Setubal ₁ , Ricardo J Giordano ₁

Affiliation

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.

中文翻译：

基于转录组的病理性血管生成签名可预测乳腺癌患者的生存率。

驱动生理性血管生成的特定基因和分子与病理性血管生成中涉及的基因和分子不同，这为这些看似相关的过程提出了不同的机制。揭示与病理性血管生成优先相关的基因和途径是了解其机制的关键，从而有助于开发新方法来管理依赖血管新生的疾病。为了更好地理解这些不同的过程，我们阐明了在公认的病理性血管生成的氧诱导性视网膜病变（OIR）模型中的小鼠视网膜的转录组。我们确定了正常和OIR视网膜之间的153个基因发生了改变，这代表了与其他依赖血管生成的过程（例如癌症）相关的分子标记。这些基因有力地预测了乳腺癌患者的生存，在一个独立的1000名患者的测试队列中进行了验证（15年生存率相差40％； p = 2.56 x 10-21）。这些结果表明，OIR模型揭示了与病理性血管生成有关的关键基因，这些可能在将肿瘤分层以进行治疗强化或靶向血管生成的疗法中具有重要的应用。

更新日期：2019-12-18

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