Discipline of Oncology, Department of Radiology & Oncology, Faculty of Medicine, University of Sao Paulo, 01246-903, Sao Paulo, Brazil.
Laboratory of Molecular Genetics, Center for Translational Research in Oncology, Cancer Institute of Sao Paulo, 01246-000, Sao Paulo, Brazil.
Biomark Med. 2020 Nov;14(16):1537-1552. doi: 10.2217/bmm-2020-0417. Epub 2020 Nov 12.
The (pleckstrin homology like domain, family A) gene family encodes proteins capable of inhibiting AKT (serine/threonine kinase) signaling through phosphoinositol binding competition. Using analysis, we found that Luminal A and B patients' short relapse-free survival was associated with low PHLDA1 or PHLDA3 and high PHLDA2 expression. In a cohort of 393 patients with luminal breast cancer evaluated by immunohistochemistry on tissue microarrays, we found a direct association of PHLDA3 expression with hormonal therapy response (p = 0.013). Our findings provide new information on the role played by the PHLDA family members as prognostic markers in breast cancer, and more importantly, we provide evidence that they might also predict a response to endocrine therapy.
(pleckstrin homology like domain, family A)基因家族编码的蛋白能够通过与磷酸肌醇结合竞争抑制 AKT(丝氨酸/苏氨酸激酶)信号。通过分析,我们发现 Luminal A 和 B 患者的无复发生存时间较短与 PHLDA1 或 PHLDA3 表达较低和 PHLDA2 表达较高有关。在一组 393 名通过组织微阵列免疫组化评估的 luminal 乳腺癌患者中,我们发现 PHLDA3 表达与激素治疗反应直接相关(p=0.013)。我们的研究结果为 PHLDA 家族成员作为乳腺癌预后标志物的作用提供了新的信息,更重要的是,我们提供了证据表明它们也可能预测内分泌治疗的反应。