MicroRNA-194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma.
MicroRNA-194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma.
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DOI：
10.1002/cam4.631
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发表时间：
2016-04
期刊：
影响因子：
4
通讯作者：
Yousef GM
中科院分区：
文献类型：
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作者：
Nofech-Mozes R;Khella HW;Scorilas A;Youssef L;Krylov SN;Lianidou E;Sidiropoulos KG;Gabril M;Evans A;Yousef GM
透明细胞肾细胞癌（ccRCC）是最常见的成人肾癌。需要预后标志物来指导患者治疗采用积极的方法还是更保守的方法，特别是对于≤4厘米的小肿瘤。据报道，miR-194 在多种癌症中表达下调，并参与上皮细胞向间质细胞的转化。我们评估 miR-194 作为 ccRCC 的预后标志物。在 234 名原发性 ccRCC 患者的队列中，我们将 miR-194 表达水平与多种临床病理学特征相关联，包括无病生存率和总生存率、肿瘤大小、临床分期和组织学分级。我们的结果显示，从正常肾脏到原发性 ccRCC，miR-194 表达逐步降低（P = 0.0032），随后从原发性病变到转移性病变降低。此外，与表达较低的患者相比，miR-194 表达较高的患者无病生存期 (P = 0.041) 和总生存期 (P = 0.031) 显着更长。在多变量分析中，miR-194 阳性肿瘤在无病生存率和总生存率方面仍具有重要意义，表明 miR-194 是 ccRCC 良好预后的独立标志物。此外，miR-194 是肾小肿块患者良好预后的标志物（P = 0.014）。这些发现在癌症基因组图谱的独立数据集上得到了验证。我们还比较了 RCC 亚型之间的 miR-194 表达。 ccRCC 的水平最高，而嫌色细胞 RCC 和嗜酸细胞瘤的水平相当低。靶标预测与通路分析相结合表明，miR-194 预计会靶向参与 RCC 进展的关键分子和通路。 miR-194 代表 ccRCC 的预后生物标志物。
Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors ≤4 cm. miR‐194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR‐194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR‐194 expression level with multiple clinicopathological features including disease‐free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR‐194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR‐194 expression has significantly longer disease‐free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR‐194‐positive tumors retain significance in disease‐free survival and overall survival, suggesting miR‐194 is an independent marker for good prognosis in ccRCC. Moreover, miR‐194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR‐194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR‐194 is predicted to target key molecules and pathways involved in RCC progression. miR‐194 represents a prognostic biomarker in ccRCC.