Iliev Robert, Fedorko Michal, Machackova Tana, Mlcochova Hana, Svoboda Marek, Pacik Dalibor, Dolezel Jan, Stanik Michal, Slaby Ondrej
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
Anticancer Res. 2016 Dec;36(12):6419-6423. doi: 10.21873/anticanres.11239.
Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively.
In our study, we analyzed piR-823 levels in 588 biological specimens: tumor tissue (N=153), adjacent renal parenchyma (N=121), blood serum (N=178) and urine (N=20) of patients undergoing nephrectomy for RCC; and in blood serum (N=101) and urine (N=15) of matched healthy controls. Expression levels of piR-823 were determined in all biological specimens by quantitative real-time polymerase chain reaction, compared in patients and controls, and correlated with clinicopathological features of RCC.
We identified a significant down-regulation of piR-823 in tumor tissue [p<0.0001, area under the curve (AUC)=0.7945]. On the contrary in blood serum and urine, the expression of piR-823 was significantly higher in patients with RCC compared to healthy individuals (p=0.0005, AUC=0.6264 and p=0.0157, AUC=0.7433, respectively). We further observed higher levels of piR-823 in tumor tissue to be associated with shorter disease-free survival of patients (p=0.0186) and a trend for higher piR-823 levels in serum to be associated with advanced clinical stages of RCC (p=0.0691). There were no other significant associations of piR-823 levels in any type of biological specimen with clinicopathological features of RCC.
piR-823 is down-regulated in tumor tissue, but positively correlated with worse outcome, indicating its complex role in RCC pathogenesis. In blood serum, piR-823 is up-regulated, but with unsatisfactory analytical performance. Preliminary data indicate the promising diagnostic utility of urinary piR-823 in patients with RCC.
肾细胞癌（RCC）是成人肾脏最常见的肿瘤，约占成人恶性肿瘤的3%。P元件诱导的弱小睾丸（PIWI）相互作用RNA（piRNA）是一类新的天然存在的短非编码RNA，参与转座元件的沉默和序列特异性染色质修饰。已有初步数据表明，piR-823的表达在胃癌和肾癌的循环肿瘤细胞及肿瘤组织中分别失调。
在我们的研究中，我们分析了588份生物标本中piR-823的水平：接受肾切除术治疗RCC患者的肿瘤组织（N = 153）、肾旁组织（N = 121）、血清（N = 178）和尿液（N = 20）；以及配对健康对照的血清（N = 101）和尿液（N = 15）。通过定量实时聚合酶链反应测定所有生物标本中piR-823的表达水平，在患者和对照中进行比较，并与RCC的临床病理特征相关联。
我们发现肿瘤组织中piR-823显著下调[p < 0.0001，曲线下面积（AUC）= 0.7945]。相反，在血清和尿液中，RCC患者中piR-823的表达显著高于健康个体（分别为p = 0.0005，AUC = 0.6264和p = 0.0157，AUC = 0.7433）。我们进一步观察到肿瘤组织中较高水平的piR-823与患者较短的无病生存期相关（p = 0.0186），血清中较高水平的piR-823有与RCC晚期临床分期相关的趋势（p = 0.069）。在任何类型的生物标本中，piR-823水平与RCC的临床病理特征均无其他显著关联。
piR-823在肿瘤组织中下调，但与较差的预后呈正相关，表明其在RCC发病机制中的复杂作用。在血清中，piR-823上调，但分析性能不理想。初步数据表明尿piR-823在RCC患者中有潜在的诊断价值。
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