Department of Pathology, Akdeniz University, School of Medicine, Antalya 07070, Turkey.
Department of Oncology, Akdeniz University, School of Medicine, Antalya 07070, Turkey.
World J Gastroenterol. 2020 Jul 14;26(26):3814-3833. doi: 10.3748/wjg.v26.i26.3814.
The role of the Notch pathway in carcinogenesis and tumor progression has been demonstrated in many organs, including the colon. Accordingly, studies aimed at developing therapies targeting this pathway in various cancers require the identification of several factors that may play a role in regulating Notch-1 expression. Although Numb, Itch, and seven in absentia homolog-1 (Siah-1) have been shown to contribute to the regulation of Notch signaling, their role in colorectal carcinogenesis and tumor progression has not been fully elucidated to date.
To evaluate Numb, Itch, and Siah-1 expression in colorectal tumors to clarify their relationship with Notch-1 expression and their role in carcinogenesis and tumor behavior.
Expression of Notch-1, Numb, Itch, and Siah-1 was investigated in 50 colorectal carcinomas, 30 adenomas, and 20 healthy colonic tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analyses.
In contrast to Notch-1, which is expressed at higher levels in tumor tissues and adenomas, expression of Numb, Itch, and Siah-1 was stronger and more frequent in normal mucosa ( < 0.01). There was a positive correlation between Notch-1 expression and high histological grade, the presence of lymph node metastasis, and advanced-stage tumors, whereas expression of Numb, Itch, and Siah-1 was absent or reduced in tumors with these clinicopathological parameters ( < 0.05). In survival analysis, expression of Notch was related to poor prognosis but that of Numb, Itch, and Siah-1 correlated with improved survival ( < 0.05). Multivariate analysis revealed Notch-1 expression and loss of Numb expression to be independent prognostic parameters together with lymph node metastasis ( < 0.05).
Our findings support the role of Notch-1 in colorectal carcinoma and indicate that loss of Numb, Itch, and Siah-1 expression is associated with carcinogenesis. Our data also suggest that these three proteins might be involved in the Notch-1 pathway during colorectal carcinoma (CRC) progression and might play an essential role in approaches targeting Notch as novel molecular therapies for CRC.
Notch 通路在包括结肠在内的许多器官的癌变和肿瘤进展中发挥作用，这已得到证实。因此，旨在开发针对各种癌症中该通路的治疗方法的研究需要鉴定可能在调节 Notch-1 表达中发挥作用的几个因素。虽然已经表明 Numb、Itch 和 absentia 同源物-1（Siah-1）有助于 Notch 信号的调节，但迄今为止，它们在结直肠癌变和肿瘤进展中的作用尚未完全阐明。
评估 Notch-1 在结直肠肿瘤中的表达，以阐明它们与 Notch-1 表达的关系及其在癌变和肿瘤行为中的作用。
通过免疫组织化学和定量实时聚合酶链反应（PCR）分析，研究了 50 例结直肠癌、30 例腺瘤和 20 例健康结肠组织中 Notch-1、Numb、Itch 和 Siah-1 的表达。
与 Notch-1 在肿瘤组织和腺瘤中表达水平较高形成对比的是，Numb、Itch 和 Siah-1 的表达在正常黏膜中更强且更频繁（<0.01）。 Notch-1 表达与高组织学分级、存在淋巴结转移和晚期肿瘤呈正相关，而具有这些临床病理参数的肿瘤中 Numb、Itch 和 Siah-1 的表达缺失或减少（<0.05）。在生存分析中，Notch 表达与预后不良相关，而 Numb、Itch 和 Siah-1 表达与改善的生存相关（<0.05）。多变量分析显示 Notch-1 表达和 Numb 表达缺失与淋巴结转移一起是独立的预后参数（<0.05）。
我们的研究结果支持 Notch-1 在结直肠癌中的作用，并表明 Numb、Itch 和 Siah-1 表达缺失与癌变有关。我们的数据还表明，这三种蛋白质可能参与结直肠癌进展过程中的 Notch-1 通路，并可能在针对 Notch 的新型分子治疗作为结直肠癌的新方法中发挥重要作用。
