Global and Targeted miRNA Expression Profiling in Clear Cell Renal Cell Carcinoma Tissues Potentially Links miR-155-5p and miR-210-3p to both Tumorigenesis and Recurrence.
Global and Targeted miRNA Expression Profiling in Clear Cell Renal Cell Carcinoma Tissues Potentially Links miR-155-5p and miR-210-3p to both Tumorigenesis and Recurrence.
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透明细胞肾细胞癌组织中的全局和靶向 miRNA 表达谱可能将 miR-155-5p 和 miR-210-3p 与肿瘤发生和复发联系起来。
DOI：
10.1016/j.ajpath.2018.07.026
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Wu,Xifeng
中科院分区：
文献类型：
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作者：
Zhang,Jinhua;Ye,Yuanqing;Chang,DavidW;Lin,Shu-Hong;Huang,Maosheng;Tannir,NizarM;Matin,Surena;Karam,JoseA;Wood,ChristopherG;Chen,Zhi-Nan;Wu,Xifeng
约30%的肾细胞癌（RCC）患者接受肾切除术后会出现疾病复发。我们分析了透明细胞（cc）RCC肿瘤组织中表达异常的miRNAs，并预测复发。在来自18名ccRCC患者的发现队列的成对肿瘤和正常组织中评估800种miRNA的表达水平。在205例患者的验证组中，使用实时定量PCR检测发现差异表达的miRNA。来自癌症基因组图谱中64名患者的肿瘤正常数据用于外部验证。28种miRNAs在肿瘤组织中持续失调。在二分分析中，高水平miR-155- 5 p和miR-210- 3 p的患者显示ccRCC复发的风险增加，（风险比，2.64; 95% CI，1.49至4.70;P= 0.0009;风险比，1.80; 95% CI，1.04至3.12; P= 0.036）和较短的中位无复发生存时间比低水平的患者[P< 0.01（对数秩检验）]。基于miR-155- 5 p和miR-210- 3 p的表达水平生成风险评分，趋势检验具有显著性（P= 0.005）。在通路分析中，miR-155- 5 p和miR-210- 3 p调控的靶基因主要富集在炎症相关通路中。我们鉴定并验证了在ccRCC组织中失调的多种miRNA; miR-155- 5 p和miR-210- 3 p可预测ccRCC复发，指出其作为生物标志物和潜在生物学机制的潜在效用。
About 30% of patients undergoing nephrectomy for renal cell carcinoma (RCC) experience disease recurrence. We profiled miRNAs dysregulated in clear-cell (cc) RCC tumor tissues and predictive of recurrence. The expression levels of 800 miRNAs were assessed in paired tumor and normal tissues from a discovery cohort of 18 ccRCC patients. miRNAs found to be differentially expressed were examined in a validation set of 205 patients, using real-time quantitative PCR. Tumor-normal data from 64 patients in The Cancer Genome Atlas were used for external validation. Twenty-eight miRNAs were consistently dysregulated in tumor tissues. On dichotomized analysis, patients with high levels of miR-155-5p and miR-210-3p displayed an increased risk for ccRCC recurrence (hazard ratio, 2.64; 95% CI, 1.49 to 4.70;P= 0.0009; and hazard ratio, 1.80; 95% CI, 1.04 to 3.12;P= 0.036, respectively) and a shorter median recurrence-free survival time than did patients with low levels [P< 0.01 (log rank test)]. A risk score was generated based on the expression levels of miR-155-5p and miR-210-3p, and the trend test was significant (P= 0.005). On pathway analysis, target genes regulated by miR-155-5p and miR-210-3p were mainly enriched in inflammation-related pathways. We identified and validated multiple miRNAs dysregulated in ccRCC tissues; miR-155-5p and miR-210-3p were predictive of ccRCC recurrence, pointing to potential utility as biomarkers and underlying biological mechanisms.