RCSI Centre for Systems Medicine, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
J Mol Med (Berl). 2018 Oct;96(10):1025-1037. doi: 10.1007/s00109-018-1675-0. Epub 2018 Aug 1.
Elevated levels of the anti-apoptotic BCL2 protein associate with favourable outcome in breast cancer. We investigated whether executioner caspase activation downstream of mitochondrial apoptosis was associated with, or independent, of BCL2's prognostic signature in breast cancer. Levels of pro- and anti-apoptotic BCL2 family proteins were quantified in triple negative breast cancer (TNBC) samples and utilised to calculate BCL2 profiles of 845 breast cancer patients. Biomarkers including single apoptosis proteins and network-enriched apoptosis system signatures were evaluated using uni- and multi-variate Cox-models. In both TNBC and non-TNBC breast cancer, the anti-apoptotic BCL2 protein was particularly abundant when compared to other solid tumours. High BCL2 protein levels were prognostic of favourable outcome across all breast cancers (HR 0.4, 95% CI 0.2-0.6, Wald p < 0.0001). Although BCL2 and cleaved caspase-7 levels were negatively correlated, levels of cleaved caspase-7 were also associated with favourable outcome (HR 0.4, 95% CI 0.3-0.7, Wald p = 0.001). A combination of low BCL2 and low cleaved caspase-7 protein levels was highly prognostic of unfavourable outcome across all breast cancers (HR 11.29, 95% CI 2.20-58.23, Wald p = 0.01). A combination of BCL2 and cleaved caspase-7 levels is a promising prognostic biomarker in breast cancer patients.
BCL2 levels are elevated in breast cancer where they are marker of good prognosis. BCL2 and active caspase levels correlate negatively; yet, active caspases indicate good outcome. Low BCL2 and low caspase-7 are highly prognostic of unfavourable outcome across all breast cancers. BCL2 levels indicate molecular subtype and tumour proliferation status in breast cancer.
抗凋亡 BCL2 蛋白水平升高与乳腺癌预后良好相关。我们研究了线粒体凋亡下游的效应子半胱天冬酶激活是否与乳腺癌中 BCL2 的预后特征相关，或是否与之独立。在三阴性乳腺癌 (TNBC) 样本中定量分析了促凋亡和抗凋亡 BCL2 家族蛋白的水平，并利用这些数据计算了 845 例乳腺癌患者的 BCL2 图谱。使用单变量和多变量 Cox 模型评估了包括单个凋亡蛋白和网络富集的凋亡系统特征在内的生物标志物。在 TNBC 和非 TNBC 乳腺癌中，与其他实体瘤相比，抗凋亡 BCL2 蛋白的水平特别高。高 BCL2 蛋白水平在所有乳腺癌中均预示预后良好 (HR 0.4, 95%CI 0.2-0.6, Wald p<0.0001)。尽管 BCL2 和裂解的 caspase-7 水平呈负相关，但裂解的 caspase-7 水平也与良好预后相关 (HR 0.4, 95%CI 0.3-0.7, Wald p=0.001)。在所有乳腺癌中，低 BCL2 和低裂解的 caspase-7 蛋白水平的组合高度预示预后不良 (HR 11.29, 95%CI 2.20-58.23, Wald p=0.01)。BCL2 和裂解的 caspase-7 水平的组合是乳腺癌患者有前途的预后生物标志物。
BCL2 水平在乳腺癌中升高，是预后良好的标志物。BCL2 和活性 caspase 水平呈负相关；然而，活性半胱天冬酶预示着良好的结果。低 BCL2 和低 caspase-7 在所有乳腺癌中均高度预示预后不良。BCL2 水平指示乳腺癌的分子亚型和肿瘤增殖状态。
