吴 婧,尹 丽,杜鸣宇.鼻咽癌中ADAM17的表达及其临床意义[J].肿瘤学杂志,2020,26(10):856-862. |
鼻咽癌中ADAM17的表达及其临床意义 |
Expression of ADAM17 in Nasopharyngeal Carcinoma and Its Clinical Significance |
投稿时间:2019-11-05 |
DOI:10.11735/j.issn.1671-170X.2020.10.B002 |
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中文关键词: 鼻咽肿瘤 免疫组化 ADMA17 预后 |
英文关键词:nasopharyngeal carcinoma immunohistochemistry ADAM17 prognosis |
基金项目:国家自然科学基金(81702692;81672989);中国博士后科学基金(2018M632266);江苏省科技厅社发重点项目(BE2019756);江苏省卫生厅青年医学人才基金 (QNRC2016648) |
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中文摘要: |
摘 要:[目的] 探讨ADAM17在鼻咽癌(nasopharyngeal carcinoma,NPC)组织中表达与临床预后的关系,及其在鼻咽癌细胞中的生物学功能。[方法] 免疫组化检测72例鼻咽癌患者和10例正常鼻咽组织标本中ADAM17的表达;Transwell小室实验检测ADAM17对鼻咽癌细胞侵袭和迁移能力的影响。分析ADAM17表达与鼻咽癌患者临床病理特征及预后的关系。[结果] ADAM17在鼻咽癌组织中的表达水平明显高于正常鼻咽组织(0.204 ± 0.016 vs 0.034 ± 0.006,P<0.01);ADAM17表达水平与年龄、性别、临床分期和肿瘤大小(T)无关(P>0.05),与淋巴结转移(N)及TNM分期有关(P<0.05)。ADAM17高表达组与低表达组患者的中位总生存期(overall survival,OS)分别为97个月 和109个月(P=0.0087)、中位无进展生存期(progression-free survival,PFS)分别为89个月 和 109个月 (P=0.0229)。COX回归单因素和多因素分析显示ADAM17表达是鼻咽癌OS的独立预后因素(HR=5.974,95%CI:1.307~27.298,P=0.021;HR=4.975,95%CI:1.016~24.368,P=0.048)。Real-time PCR和Western blot实验结果显示与鼻咽永生化上皮细胞NP69相比,ADAM17在 鼻咽癌细胞中表达明显增高,差异有统计学意义;Transwell小室实验结果显示沉默ADAM17后,与si-NC组相比,si-ADAM17组侵袭与迁移的细胞数量明显减少,差异有统计学意义。[结论] ADAM17在鼻咽癌组织和细胞中异常高表达,并与NPC的分期及不良预后密切相关,沉默ADAM17表达能够有效抑制NPC细胞的侵袭与迁移能力。提示ADAM17在鼻咽癌的侵袭转移进程中具有重要作用,有望成为NPC治疗的新靶点。 |
英文摘要: |
Abstract:[Objective] To investigate the expression of ADAM17 in nasopharyngeal carcinoma(NPC) and its clinical significance. [Methods] ADAM17 expression in 72 samples of primary NPC and 10 samples of normal nasopharyngeal tissues was determined byimmunohistochemistry. The effects of ADAM17 on the cell invasion and migration was explored by Transwellassay. The relationship of ADAM17 expression with clinicopathologicalfeatures and prognosis of NPCpatients was analyzed.[Results] The expression of ADAM17 in NPC was significantly higher than that in normal nasopharyngeal tissues(0.204±0.016 vs 0.034±0.006,P<0.01). ADAM17 expression was not correlated with age,gender,clinical stage and tumor size(T)(P>0.05),but correlated with lymph node metastasis(N) and TNM stages(P<0.05). The median overall survival(OS) of patients with high and low expression of ADAM17 were 97 months and 109 months(P=0.0087),and the median progression-free survival(PFS) was 89 months and 109 months(P=0.0229),respectively. Univariate and Multivariate analysis showed that high expression of ADAM17was an independent prognostic factor for OS of NPC patients(HR=5.974,95%CI:1.307~27.298,P=0.021;HR=4.975,95%CI:1.016~24.368,P=0.048). Real-time PCR and Western blot assays showed that ADAM17 expression was higher in NPC cell lines,compared with immortalized nasopharyngeal epithelial cell NP69. Transwell assays exhibited that down-regulation of AMAM17 significantly reduced the cell invasion and migration compared with the controls. [Conclusion] The high expression of ADAM17 in NPC tissues are closely related to clinical stage and poor prognosis of NPC patients. The knockdown of ADAM17 can effectively suppress the invasion and migration of NPC cells. ADAM17 may play an important role in the invasion and metastasis of NPC and might be a new target for NPC therapy. |
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