Notch1 and Notch2 have opposite prognostic effects on patients with colorectal cancer
Notch1 and Notch2 have opposite prognostic effects on patients with colorectal cancer
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DOI：
10.1093/annonc/mdq776
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发表时间：
2011-11-01
影响因子：
50.5
通讯作者：
Ji, G.
中科院分区：
文献类型：
--
作者：
Chu, D.;Zhang, Z.;Ji, G.
背景：异常激活的 Notch 信号传导已被证明在各种人类恶性肿瘤的致癌和进展中发挥关键作用。在本研究中，我们研究了Notch1和Notch2在结直肠癌中的表达，以确定它们是否可以作为预后预测因子。患者和方法：通过免疫组织化学方法检测1003个临床结直肠癌标本中Notch1和Notch2的蛋白表达。通过免疫组织化学研究Notch1和Notch2蛋白水平。对其预后价值进行统计分析。结果：Notch1和Notch2在结直肠癌中呈显着负相关（P<0.001）。 Notch1和Notch2被证明与肿瘤分化、浸润深度、淋巴结转移、远处转移、TNM（肿瘤-淋巴结-转移）分期和患者生存呈负相关，表明两种受体的功能相反。 Notch1 和 Notch2 被证明是不利的独立预后预测因子 (P < 0.001)。此外，Notch1 阳性和 Notch2 阴性共表达对预测较差的总生存期具有协同作用。结论：Notch1 和 Notch2 可能是结直肠癌患者的独立不良预后预测因子。这些结果将有助于确定更有效的预后预测因子和治疗靶点。
Background: Aberrantly activated Notch signaling has been shown to play a key role in carcinogenesis and progression of various human malignancies. In this study, we investigated the expression of Notch1 and Notch2 in colorectal cancer to determine whether they could serve as prognostic predictors.Patients and methods: The protein expression of Notch1 and Notch2 was examined by immunohistochemistry in 1003 clinical colorectal cancer specimens. Notch1 and Notch2 protein levels were investigated by immunohistochemistry. Statistical analysis was carried out to assess their prognostic value.Results: Significantly negative correlation between Notch1 and Notch2 was found in colorectal cancer (P < 0.001). Notch1 and Notch2 were proved to be inversely correlated with tumor differentiation, depth of invasion, lymph node metastases, distant metastasis, TNM (tumor-node-metastasis) stage and survival of patients, suggesting opposite function of the two receptors. Notch1 and Notch2 were proved to be adverse independent prognostic predictors (P < 0.001). Moreover, a synergistic effect of positive Notch1 and negative Notch2 coexpression on predicting poor overall survival was proved.Conclusions: Notch1 and Notch2 may be independent adverse prognostic predictors for patients with colorectal cancer. These results would contribute to identify more efficient prognostic predictors and therapeutic targets.