实用肿瘤学杂志 ›› 2018, Vol. 32 ›› Issue (6): 538-544.doi: 10.11904/j.issn.1002-3070.2018.06.011

• 临床研究 • 上一篇    下一篇

胃癌组织中miR-320a和CYLD的表达及与临床病理特征及预后的关系

唐淑丽, 何匡邦, 张纯慧, 程佳楠, 张艳桥   

  1. 哈尔滨医科大学附属肿瘤医院(哈尔滨 150081)
  • 收稿日期:2018-07-18 出版日期:2018-12-28 发布日期:2018-12-27
  • 通讯作者: 张艳桥, E-mail:yanqiaozhang@ems.hrbmu.edu.cn
  • 作者简介:唐淑丽, 女, (1987-), 硕士, 住院医师, 从事胃癌早期诊断标识物筛选的研究。

Expression of miR-320a and CYLD in gastric cancer and its relationship with clinicopathological characteristics and prognosis

TANG Shuli, HE Kuangbang, ZHANG Chunhui, CHENG Jianan, ZHANG Yanqiao   

  1. Harbin Medical University Cancer Hospital, Harbin 150081, China
  • Received:2018-07-18 Online:2018-12-28 Published:2018-12-27

摘要: 目的 研究miR-320a和头帕肿瘤综合征蛋白(CYLD)在胃癌患者中的表达及其与临床病理特征及预后的关系。方法 选取2013年3月—2014年11月在我院行肿瘤切除术的460例胃癌患者作为研究对象, 分别收集患者肿瘤组织及癌旁非肿瘤胃粘膜组织, 采用荧光定量PCR检测miR-320a和CYLD mRNA表达水平, 采用免疫组织化学染色法检测CYLD蛋白表达, 分析miR-320a和CYLD表达水平及其与临床病理特征及预后的关系。结果 miR-320a和CYLD mRNA在肿瘤组织中的相对表达量为(0.37±0.09)、(0.91±0.23), 在癌旁非肿瘤组织中的相对表达量为(0.86±0.15), (1.56±0.42), miR-320a和CYLD mRNA在肿瘤组织中的相对表达量与非肿瘤组织比较, 差异具有统计学意义(t=60.078, 29.113, P<0.001);CYLD蛋白在肿瘤组织中的阳性表达率43.48%与癌旁非肿瘤组织73.91%比较, 差异具有统计学意义(χ2=86.624, P=0.003);miR-320a表达水平与患者肿瘤直径和淋巴结转移有关(χ2=25.859, 13.742, P<0.05);YLD表达水平与患者TNM分期和肿瘤分化程度有关(χ2=37.725, 59.323, P<0.05)。miR-320a低表达患者中位生存期(20.36±0.56)(95% CI:19.252~21.462)与miR-320a高表达患者中位生存期(28.29个月95% CI:27.158~29.412个月)比较, 差异具有统计学意义(χ2=87.967, P<0.001);CYLD阴性表达患者中位生存期(17.70个月95% CI:16.599~18.796个月)与CYLD阳性表达患者中位生存期(26.74个月95% CI:25.474~27.997个月)比较, 差异具有统计学意义(χ2=109.887, P<0.001);miR-320a和CYLD共表达患者中位生存期(29.01个月95% CI:26.831~28.946个月)与非共表达患者中位生存期(17.13个月95% CI:17.214~19.568个月)比较, 差异具有统计学意义(χ2=117.680, P<0.001)。肿瘤组织miR-320a与CYLD mRNA表达水平呈正相关(r=0.607, P<0.001);miR-320a低表达、CYLD阴性表达、TNM分期、淋巴结转移及肿瘤分化程度是影响胃癌患者预后的独立危险因素(HR=1.939、2.180、1.561、1.719、1.608, 95% CI:1.141~3.295, 1.252~3.796, 1.014~2.403, 1.115~2.650, 1.097~2.357, P<0.05)。结论 miR-320a和CYLD在胃癌患者肿瘤组织中表达量明显降低, 与疾病发生发展及不良预后有关, 是潜在的胃癌诊断及治疗新靶点。

关键词: miR-320a, 头帕肿瘤综合征蛋白, 胃癌, 预后

Abstract: Objective The aim of this study was to investigate the expression of miR-320a and cephalospermoma syndrome protein(CYLD)in patients with gastric cancer and its relationship with clinicopathological characteristics and prognosis. Methods A total of 460 patients with gastric cancer underwent tumor resection in our hospital from March 2013 to November 2014 were enrolled.Tumor tissues, non-tumor gastric mucosa tissues and normal tissues were collected.The expression of miR-320a and CYLD at levels of mRNA and protein were detected by Real-Time PCR, immunohistochemistry and Western blotting.The relationship between the expression of miR-320a and CYLD, and the clinicopathological features & prognosis of gastric cancer patients was analyzed. Results The relative expression of miR-320a and CYLD at the mRNA level in tumor tissues was(0.37±0.09), (0.91±0.23), and the relative expression in non-tumor tissues was(0.86±0.15), (1.56±0.42), respectively.The relative expression of miR-320a and CYLD mRNA in tumor tissues was significantly different from non-tumor tissues(t=60.078, 29.113, P=0.000), the positive expression rate of CYLD protein in tumor tissues was 43.48% when compared to 73.91% in non-tumor tissues.The difference was statistically significant(χ2=86.624, P=0.003).The expression level of miR-320a was significantly associated with the diameter of the tumor and lymph node metastasis(χ2=25.859 and 13.742, P<0.05).The expression of CYLD was also significantly associated with the TNM stage and degree of tumor differentiation(χ2=37.725 and 59.323, P<0.05).The median survival of patients with low miR-320a expression(20.36 months, 95% CI:19.252~21.462 months)and those with high miR-320a expression(28.29 months, 95% CI:27.158~29.412 months)were statistically significant(χ2=87.967, P<0.001).The median survival of patients with CYLD negative expression(17.70 months, 95% CI:16.599~18.796 months)and those with CYLD positive expression(26.74 months, 95% CI:25.474~27.997 months)were statistically significant(χ2=109.887, P<0.001);The median survival of patients with the co-expressed miR-320a and CYLD was(29.01 months, 95% CI:26.831~28.946 months)and those with the non-co-expressed miR-320a and CYLD(17.13 months, 95% CI:17.214~19.568 months)were statistically significant(χ2=117.680, P<0.001).There showed a positive correlation between the expression of miR-320a and CYLD at mRNA level(r=0.607, P<0.001);miR-320a at the low expression, CYLD at the negative expression, TNM staging, lymph node metastasis and degree of tumor differentiation were independent risk factors for the prognosis of gastric cancer(HR=1.939, 2.180, 1.561, 1.719, 1.608, 95% CI:1.141~3.295, 1.252~3.796, 1.014~2.403, 1.115~2.650, 1.097~2.357, respectively)(P<0.05). Conclusion The expressions of miR-320a and CYLD in tumor tissues of patients with gastric cancer is significantly decreased, which is related to the occurrence and development of diseases, and poor prognosis.It is a potential target for diagnosis and treatment of gastric cancer.

Key words: MiR-320a, Cylindromatosis, Gastric cancer, Prognosis

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