ID2 predicts poor prognosis in breast cancer, especially in triple-negative breast cancer, and inhibits E-cadherin expression.
ID2 predicts poor prognosis in breast cancer, especially in triple-negative breast cancer, and inhibits E-cadherin expression.
复制标题
ID2预测乳腺癌，尤其是三阴性乳腺癌的不良预后，并抑制E-钙粘蛋白表达
DOI：
10.2147/ott.s64759
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发表时间：
2014
影响因子：
4
通讯作者：
Shao ZM
中科院分区：
文献类型：
--
作者：
Li K;Yao L;Chen L;Cao ZG;Yu SJ;Kuang XY;Hu X;Shao ZM
背景DNA结合（ID）蛋白的抑制剂已知是调节细胞增殖和分化的重要调节剂。本研究旨在探讨ID蛋白在乳腺癌中的预后价值。方法应用组织芯片技术检测250例乳腺癌组织中ID蛋白的表达情况，并分析其与乳腺癌预后的关系。通过定量逆转录聚合酶链反应（qRT-PCR）和蛋白质印迹法检测过表达ID的细胞中E-钙粘蛋白的信使（m）RNA和蛋白质水平。采用双荧光素酶报告试验研究其可能的作用机制，并采用迁移试验研究ID对细胞迁移活性的影响。结果Kaplan-Meier和考克斯回归分析显示，ID 2表达水平与雌激素受体状态和E-cadherin丰度相关，是影响无病生存的独立预后因素（P=0.013）。ID 2对DFS的预后价值在三阴性乳腺癌患者中最显著（P=0.009）。相关分析还发现ID 2与E-cadherin表达呈负相关（P=0.020，Pearson's R=-0.155）。随后，我们探索了生物学原理，发现ID蛋白的强制表达可以显著抑制E-cadherin的表达，从而增加乳腺上皮细胞的迁移能力。联合检测ID 2和E-cadherin的表达，将患者分为4个不同DFS的亚组（P=0.023）。结论ID 2的过表达可作为乳腺癌患者的预后指标，尤其是在三阴性乳腺癌患者中。ID蛋白仍然出乎意料地显示出抑制E-钙粘蛋白丰度。
Background Inhibitors of DNA-binding (ID) proteins are known as important modulators in the regulation of cell proliferation and differentiation. This study sought to investigate the prognostic value of ID proteins in breast cancer. Methods The prognostic role of ID proteins in human breast cancer was investigated in 250 breast cancers, via tissue microarrays. The messenger (m)RNA and protein levels of E-cadherin were examined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting, in cells overexpressing IDs. Dual-luciferase report assay was used to investigate the potential mechanism, and a migration assay was performed to investigate the influence of IDs on cell migratory activity. Results The survival analysis with Kaplan–Meier and Cox regression showed that ID2 expression level, which correlated with estrogen receptor status and E-cadherin abundance, served as an independent prognostic factor for disease-free survival (DFS) (P=0.013). The prognostic value of ID2 for DFS was most significant in triple-negative breast cancer patients (P=0.009). We also found that ID2 was negatively correlated with E-cadherin expression by correlation analysis (P=0.020, Pearson’s R=−0.155). Subsequently, we explored the biological rationale and uncovered that the enforced expression of ID proteins could suppress E-cadherin expression significantly, thus increasing the migration ability of mammary epithelial cells. Then using a combination of ID2 and E-cadherin expression, the patients were classified into four subgroups with different DFS (P=0.023). Conclusion The overexpression of ID2 can be used as a prognostic marker in breast cancer patients, especially in triple-negative breast cancer patients. ID proteins were still, unexpectedly, revealed to inhibit E-cadherin abundance.