成纤维细胞生长因子结合蛋白2过表达促进食管癌细胞的增殖

doi:10.3969/j.issn.1004-616x.2019.03.002

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (3): 180-185,192.doi: 10.3969/j.issn.1004-616x.2019.03.002

成纤维细胞生长因子结合蛋白2过表达促进食管癌细胞的增殖

孙晓男^1,2, 苑青², 杨荔艳², 张钰², 蔡岩², 徐昕², 王明荣², 郝佳洁², 贾雪梅¹

1. 安徽医科大学组织胚胎学教研室, 安徽合肥 230032;
2. 国家癌症中心/中国医学科学院北京协和医学院分子肿瘤学国家重点实验室, 北京 100021

收稿日期:2019-02-16 修回日期:2019-04-12 出版日期:2019-05-31 发布日期:2019-05-31
通讯作者: 贾雪梅,E-mail:jiaxueme@126.com;郝佳洁,E-mail:hjj8173@126.com E-mail:jiaxueme@126.com;hjj8173@126.com
作者简介:孙晓男,E-mail:18653272723@163.com。
基金资助:
国家重点研发计划项目（2016YFC1303201）；中国医学科学院医学与健康科技创新工程（2016-I2M-001）；国家自然科学基金（31471327）；基本科研业务费项目（2018PT32012）

FGFBP2 over-expresssion promoted cell proliferation in esophageal squamous carcinoma cells

SUN Xiaonan^1,2, YUAN Qing², YANG Liyan², ZHANG Yu², CAI Yan², XU Xin², WANG Mingrong², HAO Jiajie², JIA Xuemei¹

1. Department of Histology and Embryology, Anhui Medical University, Hefei 230032, Anhui;
2. National Cancer Center/State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Received:2019-02-16 Revised:2019-04-12 Online:2019-05-31 Published:2019-05-31

摘要/Abstract

摘要： 目的：检测成纤维细胞生长因子结合蛋白2（FGFBP2） mRNA在食管癌组织中的表达情况及其预后判断价值，探讨其在食管癌细胞中的作用。方法：采用组织微阵列联合RNA原位杂交技术在190例食管癌组织和42例配对癌旁正常组织中检测FGFBP2mRNA的表达情况，分析其阳性表达率，及其与食管癌患者临床病理指标和预后的关系。利用CCK-8体外增殖实验和Westernblot法检测FGFBP2敲降（转染siRNA）在食管癌细胞系中的作用。结果：RNA原位杂交结果显示，FGFBP2 mRNA在食管癌组织中的表达阳性率为25.8%（49/190），在癌旁正常组织中不表达，两者间差异显著（P<0.01）。Kaplan-Meier生存分析结果显示，FGFBP2mRNA表达与食管癌患者术后生存期显著相关（P=0.002），FGFBP2 mRNA表达阳性的患者预后较差。多因素Cox回归分析结果表明，FGFBP2 mRNA阳性表达是食管癌患者不良预后的独立预测因素（危险度为2.291，95%置信区间为1.271~4.129，P=0.006）。体外细胞实验结果表明敲降FGFBP2基因可抑制食管癌细胞系KYSE150和KYSE510的增殖。Western blot结果显示，敲降FGFBP2基因后AKT的磷酸化水平降低，ERK的磷酸化水平未发生明显变化（P>0.05）。结论：FGFBP2 mRNA在食管癌组织中表达升高，可能作为食管癌患者预后判断的分子标志物，FGFBP2高表达可能通过激活AKT通路而促进食管癌细胞增殖。

关键词: 食管癌, 成纤维细胞生长因子结合蛋白2, 预后标志, 增殖

Abstract: OBJECTIVE: This study aimed to detect the expression of human fibroblast growth factor binding protein 2 (FGFBP2) mRNA and to explore its prognostic value in esophageal squamous cell carcinoma (ESCC). METHODS:Tissue microarrays and RNA in situ hybridization (RISH) were used to detect expression of FGFBP2 mRNA in 190 cases of ESCC tissues and 42 cases of adjacent normal tissues. Proliferation assays were utilized to explore the roles of FGFBP2 in ESCC cells in vitro. RESULTS:RISH results show positive expression of FGFBP2 mRNA in 49 out 190 (25.8%) ESCC tissues,whereas no FGFBP2 mRNA signal was detected in normal surgical margins tissues (P<0.01). High expression of FGFBP2 mRNA was correlated with shorter survival time of ESCC patients (P=0.002). Cox regression analyses indicate that FGFBP2 mRNA was an independent prognostic factor in ESCC patients (HR:2.291,95%CI:1.271-4.129,P=0.006). Knockdown of FGFBP2 inhibited the proliferation of ESCC cell lines KYSE150 and KYSE510. Western blotting results demonstrate that knockdown of FGFBP2 decreased the level of phosphorylated AKT (p-AKT) but did not affect the expression of phosphorylated ERK (p-ERK) protein. CONCLUSION: Our data suggest that FGFBP2 mRNA may be a prognosis biomarker of ESCC. With respect to the mechanism, our studies show that knockdown of FGFBP2 depressed proliferation of ESCC cells through activating the AKT pathway.

Key words: esophageal squamous cell carcinoma, FGFBP2, prognostic biomarker, proliferation

中图分类号:

R735.1

孙晓男, 苑青, 杨荔艳, 张钰, 蔡岩, 徐昕, 王明荣, 郝佳洁, 贾雪梅. 成纤维细胞生长因子结合蛋白2过表达促进食管癌细胞的增殖[J]. 癌变·畸变·突变, 2019, 31(3): 180-185,192.

SUN Xiaonan, YUAN Qing, YANG Liyan, ZHANG Yu, CAI Yan, XU Xin, WANG Mingrong, HAO Jiajie, JIA Xuemei. FGFBP2 over-expresssion promoted cell proliferation in esophageal squamous carcinoma cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(3): 180-185,192.

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成纤维细胞生长因子结合蛋白2过表达促进食管癌细胞的增殖

FGFBP2 over-expresssion promoted cell proliferation in esophageal squamous carcinoma cells

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