Her-2阳性乳腺癌淋巴结转移相关miRNA鉴定功能分析与预后关系研究  

The relationship between HER-2-positive breast cancer lymph node metastasis related miRNA identification,functional analysis and prognosis

作　　者：张喜平[1] 丁先锋[2] 杨红健[1] 竺美珍[1] 赵帅 俞飞江[1] Zhang Xiping

机构地区：[1]浙江省肿瘤医院,310022 [2]浙江理工大学生命科学院,310018

出　　处：《浙江临床医学》2019年第11期1457-1460,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省医药卫生平台计划(重点资助类)(2016ZDB003)。

摘　　要：目的 筛选与乳腺癌淋巴结转移相关miRNA,探讨其在Her-2阳性乳腺癌增殖和侵袭中的作用.方法 在24例不同淋巴结转移程度的Her-2阳性乳腺癌患者的冷冻组织样本中,对从TCGA数据库中筛选出5种可能与乳腺癌淋巴结转移相关的5种miRNA进行qRT-PCR检测,比较其在不同淋巴结转移程度的肿瘤组织与癌旁组织的相对表达水平,并分析其与淋巴结转移数目、病理分期、存活率、生存时间的相关性.最后再选出两种与Her-2阳性乳腺癌淋巴结转移最相关的miRNA,进行CCK8实验和Transwell实验,检测它们对MDA-MB-453细胞增殖和侵袭的影响.结果 选出5种可能与乳腺癌淋巴结转移相关的miRNA为miR-143、miR-455、miR-196a、miR-9和miR-92a,其中仅有miR-455表达与乳腺癌患者总生存显著正相关(P<0.05).>3颗淋巴结转移组的总生存时间和存活率明显短于无淋巴结转移组(P<0.01).MiR-143-3p、miR-455-5p、miR-196a-5p、miR-9-5p的相对表达水平与Her-2阳性乳腺癌患者淋巴结转移程度相关,miR-455-5p、miR-9-5p的相对表达水平与患者病理分期相关,miR-455-5p、miR-92a-3pmiR-92a-3p存活率相关(P<0.05,P<0.01或P<0.001).细胞学实验研究显示上调miR-455显著抑制MDA-MB-453细胞的增殖和侵袭,而下调miR-143表达则显著抑制乳腺癌细胞增殖和侵袭.结论 MiR-455、miR-92a可能为抑癌因子,miR-196a、miR-9可能为促癌因子,下调miR-455和上调miR-143能够促进Her-2阳性乳腺癌细胞的增殖和侵袭.Objective To screen the miRNAs associated with lymph node metastasis of breast cancer and explore their roles in proliferation and invasion of Her-2 positive breast cancer.Methods In the frozen tissue samples of 24 patients with Her-2 positive breast cancer with different degree of lymph node metastasis,five kinds of miRNAs which may be related to lymph node metastasis of breast cancer were screened from TCGA database and detected by qRT-PCR.Their relative expression levels in different degree of lymph node metastasis were compared with those in paracancerous tissues,and the number and pathological stage of lymph node metastasis were analyzed.The correlation between survival rate and survival time.Finally,two kinds of miRNAs most related to lymph node metastasis of Her-2 positive breast cancer were selected.CCK8 and Transwell experiments were conducted to detect their effects on proliferation and invasion of MDA-MB-453 cells.Results Five possible miRNAs associated with lymph node metastasis in breast cancer were selected as miR-143,miR-455,miR-196a,miR-9 and miR-92a.Only the expression of miR-455 was positively correlated with the overall survival of breast cancer patients(P<0.05).In the clinical sample study,the total survival time and survival rate of>3 lymph node metastasis groups were significantly shorter than those of non-lymph node metastasis groups(P<0.01).The relative expression levels of miR-143-3p,miR-455-5p,miR-196a-5p and miR-9-5p were correlated with the degree of lymph node metastasis in Her-2 positive breast cancer patients.The relative expression levels of miR-455-5p and miR-9-5p were correlated with the pathological stages of patients.The survival rates of miR-455-5p and miR-92a-3p were correlated with the survival rates of patients(P<0.05,P<0.01 or P<0.001).Cytological studies showed that up-regulation of miR-455 significantly inhibited the proliferation and invasion of MDA-MB-453 cells,while down-regulation of miR-143 significantly inhibited the proliferation and invasion of breast cancer cell

关 键 词：乳腺癌 HER-2阳性 淋巴结转移 微小RNA 

分 类 号：R73[医药卫生—肿瘤]