Shu X, Hildebrandt M A, Gu J, Tannir N M, Matin S F, Karam J A, Wood C G, Wu X
Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Br J Cancer. 2017 Jan 3;116(1):77-84. doi: 10.1038/bjc.2016.392. Epub 2016 Dec 1.
Twenty to 40% localised RCC patients may experience recurrence after curative surgery. Limited miRNA predictors have been identified for ccRCC recurrence.
Through a multi-phase study design, we analysed miRNAs in tissues obtained from 203 ccRCC patients. Paired t-test was used for tumour-normal comparisons and Cox regression model was performed to compute hazard ratios (HRs) and corresponding 95% CIs.
A 17-miRNA signature was identified that can concordantly classify >95% of tumour/adjacent normal samples. Significant enrichment was found as 6 out of 17 miRNAs were associated with obesity (binomial probability=0.001). Decreased levels of miR-204-5p and miR-139-5p were each associated with an approximately three-fold increased risk of recurrence (P<0.01). Risk score was generated based on expressions of miR-204-5p and miR-139-5p, and the trend test was significant in both discovery and validation sets (P<0.05). Striking MST reduction was observed for patients with a high-risk score (high vs low: discovery, 9.4 vs >97.7 months; validation, 20.8 vs >70.3 months). Expressions of miR-204-5p were also associated with body mass index (β=5.64, P<0.001). Significant inverse correlations were observed and validated between miR-204-5p and 13 obesity-related genes (r<0, P<0.01).
We identified 17 miRNAs dysregulated in ccRCC tissues and showed that low expressions of miR-204-5p and miR-139-5p were associated with the higher risk of recurrence. The link between miR-204-5p and ccRCC recurrence may be partially mediated by regulating the expression of targeted obesity-related genes.
20%至40%的局限性肾细胞癌（RCC）患者在根治性手术后可能会复发。目前已确定的用于预测透明细胞肾细胞癌（ccRCC）复发的微小RNA（miRNA）指标有限。
通过多阶段研究设计，我们分析了203例ccRCC患者组织中的miRNA。采用配对t检验进行肿瘤与正常组织的比较，并进行Cox回归模型计算风险比（HRs）及相应的95%置信区间（CIs）。
鉴定出一个由17个miRNA组成的特征图谱，其可一致地将>95%的肿瘤/相邻正常样本分类。发现有显著富集现象，因为17个miRNA中有6个与肥胖相关（二项式概率=0.001）。miR-204-5p和miR-139-5p水平降低各自与复发风险增加约三倍相关（P<0.01）。基于miR-204-5p和miR-139-5p的表达生成风险评分，且趋势检验在发现集和验证集均具有显著性（P<0.05）。观察到高风险评分患者的中位生存时间（MST）显著缩短（高风险与低风险：发现集，9.4个月对>97.7个月；验证集，20.8个月对>70.3个月）。miR-204-5p的表达也与体重指数相关（β=5.64，P<0.001）。观察并验证了miR-204-5p与13个肥胖相关基因之间存在显著的负相关（r<0，P<0.01）。
我们鉴定出在ccRCC组织中失调的17个miRNA，并表明miR-204-5p和miR-139-5p的低表达与较高的复发风险相关。miR-204-5p与ccRCC复发之间的联系可能部分是通过调节靶向肥胖相关基因的表达来介导的。
