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The prognostic potential and oncogenic effects of PRR11 expression in hilar cholangiocarcinoma

机译:PRR11表达在肝门胆管癌中的预后潜力和致癌作用

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摘要

PRR11 is a newly identified oncogene in lung cancer, yet its role in others tumors remains unclear. Gastrointestinal tissue microarrays were used to evaluate PRR11 expression and its association with clinical outcome was analyzed in patients with hilar cholangiocarcinoma. Overexpression of PRR11 was observed in esophageal, gastric, pancreatic, colorectal, and hilar cholangiocarcinoma. Expression of PRR11 correlated with lymph node metastasis and CA199 level in two HC patient cohorts. After an R0 resection, a high level of PRR11 expression was found to be an independent indicator of recurrence (P = 0.001). In cell culture, PRR11 silencing resulted in decreased cellular proliferation, cell migration, tumor growth of QBC939 cells. Microarray analysis revealed that several genes involved in cell proliferation, cell adhesion, and cell migration were altered in PRR11-knockout cells, including: vimentin (VIM), Ubiquitin carboxyl-terminal hydrolase 1 (UCHL1), early growth response protein (EGR1), and System A amino acid transporter1 (SNAT1). Silencing PRR11 inhibited the expression of UCHL1, EGR1, and SNAT1 proteins, with immunoassays revealing a significant correlation among the levels of these four proteins. These results indicate that PRR11 is an independent prognostic indicator for patients with HC.
机译:PRR11是一种新近鉴定的肺癌致癌基因,但其在其他肿瘤中的作用仍不清楚。胃肠道组织微阵列用于评估PRR11表达,并分析其与肺门胆管癌患者的临床结局。在食道,胃,胰腺,结直肠和肝门胆管癌中观察到PRR11的过表达。在两个HC患者队列中,PRR11的表达与淋巴结转移和CA199水平相关。 R0切除后,发现高水平的PRR11表达是复发的独立指标(P = 0.001)。在细胞培养中,PRR11沉默导致QBC939细胞的细胞增殖,细胞迁移和肿瘤生长减少。芯片分析显示,PRR11基因敲除细胞中涉及细胞增殖,细胞黏附和细胞迁移的几个基因发生了变化,包括:波形蛋白(VIM),泛素羧基末端水解酶1(UCHL1),早期生长反应蛋白(EGR1),和系统A氨基酸转运蛋白1(SNAT1)。沉默PRR11可抑制UCHL1,EGR1和SNAT1蛋白的表达,免疫分析显示这四种蛋白的水平之间存在显着相关性。这些结果表明PRR11是HC患者的独立预后指标。

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