机构地区:[1]四川省成都大学临床医学2020级,成都610000 [2]新疆医科大学附属肿瘤医院,乌鲁木齐830011 [3]新疆医科大学基础医学院,乌鲁木齐830017 [4]新疆医科大学第一附属医院,乌鲁木齐830054
出 处:《新疆医科大学学报》2025年第4期432-437,446,共7页Journal of Xinjiang Medical University
基 金:新疆维吾尔自治区自然科学基金重点项目(2024D01D21)。
摘 要:目的探讨miR-191/425基因簇及其靶基因肾上腺髓质素2(Recombinant adrenomedullin 2,ADM2)、异连蛋白α(Dystrobrevin alpha,DTNA)、小整合膜蛋白11B(Homo sapiens small integral membrane protein 11B,SMIM11B)在食管癌组织中的表达,及与食管癌预后风险的关系。方法应用肿瘤基因组图谱(TCGA)数据库生物信息学工具分析食管癌miR-191/425基因簇及其靶基因对食管癌预后的影响;RT-qPCR验证36例食管癌组织miR-191/425基因簇及其靶基因ADM2、DTNA、SMIM11B在肿瘤组织中的表达,分析miR-191/425异常表达对食管癌发病风险的影响,利用受试者特征曲线(ROC)评价miR-191/425基因簇对食管癌的诊断效力。结果(1)生物信息学分析显示,ADM2、DTNA、SMIM11B低表达与食管癌患者的预后差有关。(2)RT-qPCR结果显示,食管癌组织中miR-191、miR-425表达显著上调,肿瘤组织中miR-191的表达上调与肿瘤T3+T4临床分期相关,miR-191和miR-425的表达呈显著正相关(r=0.639,P=0.000)。(3)Logistic回归分析显示,miR-191表达水平与食管癌的发病风险呈正相关[OR(95%CI)为:1.199(1.036~1.386),P<0.05];ROC分析显示,miR-191曲线下面积(AUC)为0.650(P<0.05)。(4)临床病理因素分析显示,在T3+T4期、淋巴结转移的肿瘤组织中DTNA mRNA的表达水平显著升高,ADM2 mRNA、SMIM11B mRNA无显著差异。(5)36例食管癌组织中DTNA mRNA的表达与miR-191和miR-425的表达呈显著正相关。结论在食管癌发生发展中,miR-191/425基因簇共同高表达增强了肿瘤细胞的侵袭,其机制可能与共同促进DTNA靶基因的表达有关,miR-191可能作为一个主要因素对食管癌具有诊断效力。Objective To investigate the expression of miR-191/425 gene cluster and its target genes recombinant adrenomedullin 2(ADM2),Dystrobrevin alpha(DTNA),homo sapiens small integral membrane protein 11B(SMIM11B)in esophageal cancer tissues,and their relationship with the prognostic risk of esophageal cancer.Methods The Tumor Genome Atlas(TCGA)database bioinformatics tool was used to analyze the impact of miR-191/425 gene cluster and its target genes on the prognosis of esophageal cancer;RT-qPCR was used to verify the expression of miR-191/425 gene cluster and its target genes ADM2,DTNA,and SMIM11B in 36 cases of esophageal cancer tissues.The impact of abnormal expression of miR-191/425 on the risk of esophageal cancer was analyzed,and the diagnostic efficacy of miR-191/425 gene cluster for esophageal cancer was evaluated using receiver operating characteristic(ROC)curve.Results(1)Bioinformatics analysis showed that low expression of ADM2,DTNA and SMIM11B was associated with poor prognosis of the patients with esophageal cancer.(2)The expressions of miR-191 and 425 were significantly up-regulated in esophageal cancer tissues,and the up-regulated expression of miR-191 in tumor tissues was correlated with the clinical staging of tumor T3+T4,and the expressions of miR-191 and miR-425 were significantly positively correlated(r=0.639,P=0.000).(3)Logistic regression analysis showed that the expression level of miR-191 was positively correlated with the risk of esophageal cancer[OR(95%CI)values were:1.199(1.036,1.386),P<0.05].ROC analysis showed that the area under the curve(AUC)of miR-191 was 0.650(P<0.05);(4)The clinicopathological factor analysis showed that the expression level of DTNA mRNA was significantly increased in T3+T4 tumor tissues and lymphatic metastasis,but there was no significant difference in ADM2 mRNA and SMIM11B mRNA.(5)The high expression of DTNA mRNA was significantly positively correlated with the expression of miR-191 and miR-425 in 36 esophageal cancer tissues.Conclusion The co-high expression of miR
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