目的探讨驱动蛋白超家族4A(kinesin family member 4A,KIF4A)在乳腺癌中的表达及与临床病理特征、预后的关系。方法利用GEO数据库的GSE3494公共数据集和TCGA数据库的乳腺癌样本及其临床资料,采用χ2检验进行KIF4A与临床病理特征的相关...目的探讨驱动蛋白超家族4A(kinesin family member 4A,KIF4A)在乳腺癌中的表达及与临床病理特征、预后的关系。方法利用GEO数据库的GSE3494公共数据集和TCGA数据库的乳腺癌样本及其临床资料,采用χ2检验进行KIF4A与临床病理特征的相关性分析,Kaplan-Meier法进行生存分析。通过基因富集分析预测乳腺癌中高表达KIF4A所富集的基因集。结果 KIF4A在不同Elston组织学分级和TNM分期的乳腺癌肿瘤样本中表达差异有统计学意义(P=0.000)。GSE3494和TCGA数据库中KIF4A与ER水平、PR水平均显著相关(P=0.000);与年龄仅TCGA数据库分析结果差异有统计学意义(P=0.000)。此外,GSE3494数据集中,KIF4A与肿瘤大小、淋巴结浸润均显著相关(P=0.000);TCGA数据库中,KIF4A仅与T分期显著相关(P=0.000),与N分期(P=0.081)、M分期(P=0.372)均不相关。KIF4A高表达的乳腺癌患者预后较差,其疾病特异生存期(P=0.001)和总体生存率(P=0.005)均远低于KIF4A低表达患者,且富集了与细胞分裂、细胞周期调控、DNA复制及DNA损伤修复有关的基因集。结论 KIF4A与乳腺癌多个临床病理指标相关,可作为潜在的乳腺癌预后标志物和治疗靶标进一步研究。展开更多
Background:microRNA-139(miR-139)is dysregulated in various types of tumors and plays a key role in carcinogenesis.miR-139 may be used as a diagnostic and prognostic biomarker of cancers.However,the data from the liter...Background:microRNA-139(miR-139)is dysregulated in various types of tumors and plays a key role in carcinogenesis.miR-139 may be used as a diagnostic and prognostic biomarker of cancers.However,the data from the literature are not consistent.The present study aimed to verify the prognostic and diagnostic values of miR-139 in solid tumors.Data sources:PubMed,Web of Science and Embase databases were searched and publications from January 2011 to August 2017 were included.We used Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)database to further validate this meta-analysis.Results:Eight individual studies from seven articles were included.Pooled analyses showed that low miR-139 expression was related to worse overall survival(OS)[hazard ratio(HR)=2.27;95%confidence intervals(CI):1.74–2.95;P<0.001]in solid tumors,including hepatocellular carcinoma(HCC)and glioblastoma multiforme(GBM),consisting with the results of TCGA.However,our results of CRC showed that low miR-139 expression was associated with poor OS which was contradictory with the results in TCGA database and need larger samples to validate the phenomenon;whereas for CRC patients,high miR-139 expression predicted poor RFS,which was in good accordance with TCGA results.The results of 27 microarrays from GEO database showed that miR-139 expression levels were lower in tumor tissues compared to adjacent non-tumor tissues or healthy tissues.Decreased miR-139 expression was also significantly correlated with poor differentiation grade(OR=3.57;95%CI:1.44–8.85;P=0.006).However,the combined data indicated that no associations between miR-139 expression and the following parameters such as age(pooled OR=1.50;95%CI:0.69–3.24;P=0.304),gender(pooled OR=0.92;95%CI:0.56–1.51;P=0.738),tumor size(pooled OR=1.51;95%CI:0.69–3.31;P=0.298),late tumor-node-metastasis stage(pooled OR=1.63;95%CI:0.99–2.68;P=0.057)and lymph-node-metastasis(pooled OR=0.66;95%CI:0.34–1.28;P=0.222).Conclusions:Low miR-139 expression was related to poor prognosis in HCC and GBM,which could be regarded as a potential prognostic biomarker.However,its precise functional role in CRC still need to be further investigated through larger samples and multicenter studies.展开更多
文摘目的探讨驱动蛋白超家族4A(kinesin family member 4A,KIF4A)在乳腺癌中的表达及与临床病理特征、预后的关系。方法利用GEO数据库的GSE3494公共数据集和TCGA数据库的乳腺癌样本及其临床资料,采用χ2检验进行KIF4A与临床病理特征的相关性分析,Kaplan-Meier法进行生存分析。通过基因富集分析预测乳腺癌中高表达KIF4A所富集的基因集。结果 KIF4A在不同Elston组织学分级和TNM分期的乳腺癌肿瘤样本中表达差异有统计学意义(P=0.000)。GSE3494和TCGA数据库中KIF4A与ER水平、PR水平均显著相关(P=0.000);与年龄仅TCGA数据库分析结果差异有统计学意义(P=0.000)。此外,GSE3494数据集中,KIF4A与肿瘤大小、淋巴结浸润均显著相关(P=0.000);TCGA数据库中,KIF4A仅与T分期显著相关(P=0.000),与N分期(P=0.081)、M分期(P=0.372)均不相关。KIF4A高表达的乳腺癌患者预后较差,其疾病特异生存期(P=0.001)和总体生存率(P=0.005)均远低于KIF4A低表达患者,且富集了与细胞分裂、细胞周期调控、DNA复制及DNA损伤修复有关的基因集。结论 KIF4A与乳腺癌多个临床病理指标相关,可作为潜在的乳腺癌预后标志物和治疗靶标进一步研究。
基金supported by grants from the National S&T Major Project of China(2018ZX10301201)the National Natu-ral Science Foundation of China(81702757,81702346,81600506,81702927,81500127)+1 种基金Youth Innovation Fund of the First Affiliated Hospital of Zhengzhou University(YNQN2017167,YNQN2017031 and YNQN2017032)the Joint Research Fund of the First Affiliated Hospital of Zhengzhou University and Dalian Institute of Chemical Physics Chinese Academy of Sciences
文摘Background:microRNA-139(miR-139)is dysregulated in various types of tumors and plays a key role in carcinogenesis.miR-139 may be used as a diagnostic and prognostic biomarker of cancers.However,the data from the literature are not consistent.The present study aimed to verify the prognostic and diagnostic values of miR-139 in solid tumors.Data sources:PubMed,Web of Science and Embase databases were searched and publications from January 2011 to August 2017 were included.We used Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)database to further validate this meta-analysis.Results:Eight individual studies from seven articles were included.Pooled analyses showed that low miR-139 expression was related to worse overall survival(OS)[hazard ratio(HR)=2.27;95%confidence intervals(CI):1.74–2.95;P<0.001]in solid tumors,including hepatocellular carcinoma(HCC)and glioblastoma multiforme(GBM),consisting with the results of TCGA.However,our results of CRC showed that low miR-139 expression was associated with poor OS which was contradictory with the results in TCGA database and need larger samples to validate the phenomenon;whereas for CRC patients,high miR-139 expression predicted poor RFS,which was in good accordance with TCGA results.The results of 27 microarrays from GEO database showed that miR-139 expression levels were lower in tumor tissues compared to adjacent non-tumor tissues or healthy tissues.Decreased miR-139 expression was also significantly correlated with poor differentiation grade(OR=3.57;95%CI:1.44–8.85;P=0.006).However,the combined data indicated that no associations between miR-139 expression and the following parameters such as age(pooled OR=1.50;95%CI:0.69–3.24;P=0.304),gender(pooled OR=0.92;95%CI:0.56–1.51;P=0.738),tumor size(pooled OR=1.51;95%CI:0.69–3.31;P=0.298),late tumor-node-metastasis stage(pooled OR=1.63;95%CI:0.99–2.68;P=0.057)and lymph-node-metastasis(pooled OR=0.66;95%CI:0.34–1.28;P=0.222).Conclusions:Low miR-139 expression was related to poor prognosis in HCC and GBM,which could be regarded as a potential prognostic biomarker.However,its precise functional role in CRC still need to be further investigated through larger samples and multicenter studies.
