基于TCGA数据库探讨胃癌组织中miR-96、BDNF表达变化和临床病理意义

Expression and Clinicopathological Significance of miR-96 and BDNF in Gastric Carcinoma Based on TCGA Database

目的观察胃癌组织中微小RNA-96(miR-96)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)mRNA表达变化,并探讨其临床病理意义。方法从包含TCGA数据网站下载胃癌患者数据集,按照miR-96表达水平由高到低排序,将排在前50%的患者设为高表达组(n=181),其余设为低表达组(n=181),并比较2组患者生存曲线。将数据集中包含的所有mRNA表达水平逐一与miR-96表达水平进行Pearson相关性检验,根据相关系数选取与miR-96表达水平相关性最高的基因。收集经手术切除、病理证实的80例胃癌组织及相应的癌周组织,检测组织中miR-96、BDNF mRNA表达水平,并观察其在胃癌组织和癌周组织中的表达情况,及其与患者年龄、性别、肿瘤直径、分化程度、淋巴结转移、TNM分期和Luaren分型的关系,并分析二者的相关性。结果miR-96高表达组中位生存时间高于miR-96低表达(P<0.05);miR-96与BDNF mRNA表达相关性最高。miR-96 mRNA在胃癌组织中表达量明显低于癌周组织,BDNF mRNA在胃癌组织中表达量明显高于癌周组织(P<0.05)。miR-96低表达、BDNF高表达与肿瘤分化程度、淋巴结转移、TNM分期及Luaren分型有关(P<0.05,P<0.01)。胃癌组织中miR-96、BDNF mRNA表达呈显著负相关(r=-0.342,P<0.01)。结论miR-96低表达、BDNF高表达与胃癌的发生、侵袭转移及恶性程度增加有关,miR-96可能通过靶向调控BDNF来抑制胃癌进展。

Objective To observe the changes of miR-96 and brain-derived neurotrophic factor(BDNF)mRNA expression in gastric cancer tissues and to explore its clinicopathological significance.Methods The dataset of gastric cancer patients was downloaded from the website containing TCGA data.According to the miR-96 expression level,the patients with top 50%of high expressions were assigned to the high expression group(n=181)and the remaining patients to the low expression group(n=181).The survival curves of the two groups were compared.All the mRNA expression levels contained in the dataset were tested for Pearson correlation with the miR-96 expression level one by one,and the genes with the highest correlation with the miR-96 expression level were selected according to the correlation coefficient.Eighty cases of gastric cancer tissues and adjacent normal tissues were obtained by surgical resection and confirmed by pathological examination.The expressions of miR-96 and BDNF mRNA were detected.The expression of miR-96 and BDNF mRNA in gastric cancer tissues and adjacent normal tissues were compared,and their relationship with age,sex,tumor diameter,differentiation degree,lymph node metastasis,TNM staging and Luaren typing were observed.In addition,the correlation between the two factors was analyzed.Results The median survival time of patients with high expression of miR-96 was significantly longer than that of patients with low expression of miR-96(P<0.05),and the correlation between miR-96 and BDNF mRNA expression was the highest.The expression of miR-96 in gastric cancer tissues was significantly lower than adjacent normal tissues,and the expression of BDNF mRNA in gastric cancer tissues was significantly higher than adjacent normal tissues(P<0.05).Low expression of miR-96 and high expression of BDNF were associated with tumor differentiation,lymph node metastasis,TNM stage and Luaren classification(P<0.05,P<0.01).There was a significant negative correlation between miR-96 and BDNF mRNA expression in gastric cancer tissues(r=-0.342,P<0.01).Conclusion Down-regulated expression of miR-96 and up-regulated expression of BDNF are associated with the pathogenesis,invasion,metastasis and increased malignancy of gastric cancer,and miR-96 may inhibit the progression of gastric cancer by targeting BDNF.