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差异表达miRNA在骨肉瘤患者中的表达情况及其与生存预后的关联性分析
刘 琦,钱 军,曹 娟,杨 倩
河西学院附属张掖人民医院骨科,甘肃 734000
摘要:
[摘要] 目的 分析差异表达miRNA在骨肉瘤(OS)患者中的表达情况及其与生存预后的关联性。方法 利用生物信息学分析方法识别GSE69470和GSE70367数据集中的差异表达miRNA。招募2018年8月至2019年1月就诊于河西学院附属张掖人民医院的63例OS患者。通过实时荧光定量聚合酶链反应(RT-qPCR)法检测并比较OS组织及癌旁组织中的差异表达miRNA表达水平。通过电话或门诊复查方式进行随访并记录患者的生存情况,术后随访5年,随访时间截至2024年1月。采用Kaplan-Meier法分析OS组织中的差异表达miRNA表达情况与OS患者生存预后的关联性。结果 生物信息学分析得出8个差异表达miRNA,包括miR-543、miR-495-3p、miR-433-3p、miR-381-3p、miR-301a-3p、miR-199b-5p、miR-125b-5p、miR-218。RT-qPCR结果显示,OS组织中的miR-543、miR-495-3p、miR-125b-5p相对表达量低于癌旁组织,miR-433-3p、miR-381-3p、miR-301a-3p、miR-199b-5p相对表达量高于癌旁组织,差异均有统计学意义(P<0.05),miR-218在OS组织和癌旁组织中的表达水平比较差异无统计学意义(P>0.05)。以每种miRNA相对表达量的中位数为界限进行分组,高表达组(>中位数)为31例,低表达组(≤中位数)为32例。Kaplan-Meier法分析结果显示,miR-543、miR-495-3p、miR-125b-5p高表达组生存预后优于低表达组,miR-433-3p、miR-381-3p、miR-301a-3p、miR-199b-5p低表达组生存预后优于高表达组,差异均有统计学意义(P<0.05)。结论 OS组织中的miR-543、miR-495-3p、miR-125b-5p相对表达量低于癌旁组织,miR-433-3p、miR-381-3p、miR-301a-3p、miR-199b-5p相对表达量高于癌旁组织,以上7个差异表达miRNA与OS患者的生存预后相关。
关键词:  差异表达miRNA  骨肉瘤  生物信息学分析  miRNA  生存预后
DOI:10.3969/j.issn.1674-3806.2024.11.11
分类号:R 735
基金项目:甘肃省卫生健康行业科研项目(编号:GSWSKY2022-58)
Analysis on the expression of differentially expressed miRNA in osteosarcoma patients and its correlation with survival prognosis
LIU Qi, QIAN Jun, CAO Juan, YANG Qian
Department of Orthopaedics, Zhang Ye People′s Hospital Affiliated to Hexi University, Gansu 734000, China
Abstract:
[Abstract] Objective To analyze the expression of differentially expressed miRNA in osteosarcoma(OS) patients and its correlation with survival prognosis. Methods The bioinformatics analysis method was used to identify differentially expressed miRNA in GSE69470 and GSE70367 datasets. Sixty-three OS patients who visited their doctors in Zhang Ye People′s Hospital Affiliated to Hexi University from August 2018 to January 2019 were recruited. Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the expression levels of differentially expressed miRNA in OS tissues and their paracancer tissues, and the expression level of differentially expressed miRNA in the OS tissues was compared with that in the paracancer tissues. The patients were followed up by telephone or outpatient reexamination methods and their survival situation was recorded. The patients were followed up for 5 years until January 2024. The Kaplan-Meier method was used to analyze the correlation between the differentially expressed miRNA expression in OS tissues and the survival prognosis of the OS patients. Results Eight differentially expressed miRNA were obtained by bioinformatics analysis, including microRNA(miR)-543, miR-495-3p, miR-433-3p, miR-381-3p, miR-301a-3p, miR-199b-5p, miR-125b-5p and miR-218. The results of RT-qPCR showed that the relative expression levels of miR-543, miR-495-3p and miR-125b-5p in the OS tissues were lower than those in the paracancer tissues, while the relative expression levels of miR-433-3p, miR-381-3p, miR-301a-3p and miR-199b-5p in the OS tissues were higher than those in the paracancer tissues, and the differences were statistically significant(P<0.05). There was no statistically significant difference in the expression level of miR-218 between the OS tissues and the paracancer tissues(P>0.05). The patients were grouped according to the median relative expression of each miRNA: 31 cases in the high expression group(>median value) and 32 cases in the low expression group(≤median value).The analysis results of Kaplan-Meier method showed that the survival prognosis in the miR-543 high expression group, the miR-495-3p high expression group and the miR-125b-5p high expression group were better than that in the miR-543 low expression group, the miR-495-3p low expression group and the miR-125b-5p low expression group, respectively, and that the survival prognosis in the miR-433-3p low expression group, the miR-381-3p low expression group, the miR-301a-3p low expression group and the miR-199b-5p low expression group was better than that in the miR-433-3p high expression group, the miR-381-3p high expression group, the miR-301a-3p high expression group and the miR-199b-5p high expression group, respectively, and the differences were statistically significant(P<0.05). Conclusion The relative expression levels of miR-543, miR-495-3p and miR-125b-5p in the OS tissues are lower than those in the paracancer tissues, while the relative expression levels of miR-433-3p, miR-381-3p, miR-301a-3p and miR-199b-5p in the OS tissues are higher than those in the paracancer tissues. The above 7 kinds of differentially expressed miRNA are associated with the survival prognosis of the OS patients.
Key words:  Differentially expressed miRNA  Osteosarcoma  Bioinformatics analysis  MicroRNA(miR)  Survival prognosis