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水通道蛋白 1 是一种预后标志物,通过下调肝内胆管癌中 Snail 的表达来抑制肿瘤进展。

Aquaporin 1 is a prognostic marker and inhibits tumour progression through downregulation of Snail expression in intrahepatic cholangiocarcinoma.

机构信息

Department of Digestive Medicine, Second Affiliated Hospital, Anhui Medical College, Anhui 230000, China; Department of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai 200438, China.

Department of Digestive Medicine, First people's Hospital of Honghe autonomous Prefecture, Yunnan Province 661199, China.

出版信息

Dig Liver Dis. 2023 Aug;55(8):1133-1140. doi: 10.1016/j.dld.2022.12.016. Epub 2023 Jan 13.

Abstract

BACKGROUND

Recently, some studies have suggested a link between AQP1 and cancer progression.

AIMS

The aim of the present study was to investigate the influence of AQP1 on the clinicopathology and prognosis of intrahepatic cholangiocarcinoma (ICC) patients.

METHODS

We retrospectively detected the expression of AQP1 protein in 307 patients with ICC who underwent partial hepatectomy. Western blot analysis was used to detect AQP1 protein levels in stable AQP1 overexpression and knockdown cell lines. The influence of AQP1 on the invasion and metastasis ability of ICC cells was assessed by wound-healing and Transwell assays in vitro as well as by a splenic liver metastasis model in vivo.

RESULTS

Positive membranous AQP1 expression was identified in 34.2% (105/307) of the ICC specimens. Survival data revealed that positive AQP1 expression was significantly associated with favourable disease-free survival (DFS) and overall survival (OS) (p = 0.0290 and p = 0003, respectively). Moreover, high AQP1 expression inhibited the invasion and migration of ICC cells in vitro as well as inhibited liver metastasis in nude mice. Mechanistically, high AQP1 expression in ICC cells increased the levels of E-cadherin but decreased the levels of the Snail transcription factor.

CONCLUSIONS

AQP1 expression is associated with a favourable prognosis in ICC patients. AQP1 inhibits ICC cell invasion, metastasis, and epithelial-mesenchymal transition (EMT) through downregulation of Snail expression.

摘要

背景

最近,一些研究表明 AQP1 与癌症进展之间存在关联。

目的

本研究旨在探讨 AQP1 对肝内胆管癌(ICC)患者临床病理特征和预后的影响。

方法

我们回顾性检测了 307 例接受部分肝切除术的 ICC 患者中 AQP1 蛋白的表达。Western blot 分析用于检测稳定过表达和敲低 AQP1 的细胞系中 AQP1 蛋白水平。通过体外划痕愈合和 Transwell 分析以及体内脾脏肝转移模型评估 AQP1 对 ICC 细胞侵袭和转移能力的影响。

结果

在 307 例 ICC 标本中,有 34.2%(105/307)的标本中存在阳性膜 AQP1 表达。生存数据分析显示,AQP1 阳性表达与较好的无病生存(DFS)和总生存(OS)显著相关(p=0.0290 和 p=0.0003)。此外,高 AQP1 表达抑制 ICC 细胞在体外的侵袭和迁移,并抑制裸鼠的肝转移。机制上,ICC 细胞中高 AQP1 表达增加了 E-钙黏蛋白的水平,但降低了 Snail 转录因子的水平。

结论

AQP1 表达与 ICC 患者的良好预后相关。AQP1 通过下调 Snail 表达抑制 ICC 细胞的侵袭、转移和上皮间质转化(EMT)。

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