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胃腺癌预测性长链基因间非编码RNA的上调促进肝门周围胆管癌进展并预示不良预后。

Upregulation of gastric adenocarcinoma predictive long intergenic non-coding RNA promotes progression and predicts poor prognosis in perihilar cholangiocarcinoma.

作者信息

Wang Xin-Ping, Song Jing, Liu Gui-Ting, Wang Jian-Jun, Guo Hai-Feng

机构信息

Department of General Surgery, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang 157011, P.R. China.

Department of Urology, Hongqi Hospital of Mudanjiang Medical College, Mudanjiang, Heilongjiang 157011, P.R. China.

出版信息

Oncol Lett. 2018 Sep;16(3):3964-3972. doi: 10.3892/ol.2018.9137. Epub 2018 Jul 11.

Abstract

Perihilar cholangiocarcinoma (PHCC) is one of the most aggressive and complex types of cancer with a poor survival. Despite advances in PHCC diagnosis and treatment, the biology of this tumor remains poorly understood. Recent studies have suggested long non-coding RNAs (lncRNAs) as crucial determinants of cancer progression. However, the role of lncRNAs in PHCC is rarely reported and the function of gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in PHCC has yet to be elucidated. The present study observed a significant upregulation of GAPLINC in PHCC cell lines and clinical specimens (P<0.05). Furthermore, by comparing clinicopathological characteristics with expression data, high GAPLINC expression was revealed to be associated with the T stage (P=0.013), N stage (P<0.001) and Tumor-Node-Metastasis stage (P<0.001) of PHCC. Furthermore, Kaplan-Meier analysis demonstrated that GAPLINC expression was associated with poor overall survival and progression-free survival rates in PHCC. Furthermore, univariate and multivariate COX regression analyses identified high GAPLINC expression as a risk factor of a poor prognosis in PHCC. GAPLINC upregulation promoted the migration and invasion of PHCC cells in Transwell and Matrigel assays, respectively, while GAPLINC deficiency inhibited PHCC cell metastasis. Furthermore, PHCC cells with GAPLINC overexpression exhibited markedly increased proliferation ability in a Cell Counting kit-8 assay. However, GAPLINC interference significantly suppressed cell proliferation. In conclusion, GAPLINC may promote PHCC progression and may serve as a potential prognostic marker and therapeutic target of PHCC.

摘要

肝门部胆管癌(PHCC)是侵袭性最强、最复杂的癌症类型之一,生存率很低。尽管PHCC的诊断和治疗取得了进展,但这种肿瘤的生物学特性仍知之甚少。最近的研究表明,长链非编码RNA(lncRNAs)是癌症进展的关键决定因素。然而,lncRNAs在PHCC中的作用鲜有报道,胃腺癌预测性长链基因间非编码RNA(GAPLINC)在PHCC中的功能尚待阐明。本研究观察到PHCC细胞系和临床标本中GAPLINC显著上调(P<0.05)。此外,通过将临床病理特征与表达数据进行比较,发现GAPLINC高表达与PHCC的T分期(P=0.013)、N分期(P<0.001)和肿瘤-淋巴结-转移分期(P<0.001)相关。此外,Kaplan-Meier分析表明,GAPLINC表达与PHCC患者较差的总生存率和无进展生存率相关。此外,单因素和多因素COX回归分析确定GAPLINC高表达是PHCC预后不良的危险因素。在Transwell和基质胶实验中,GAPLINC上调分别促进了PHCC细胞的迁移和侵袭,而GAPLINC缺失则抑制了PHCC细胞转移。此外,在细胞计数试剂盒-8实验中,过表达GAPLINC的PHCC细胞增殖能力显著增强。然而,干扰GAPLINC可显著抑制细胞增殖。总之,GAPLINC可能促进PHCC进展,并可能作为PHCC潜在的预后标志物和治疗靶点。

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