Cui Mingyu, Liu Wei, Zhang Lijuan, Guo Feng, Liu Yang, Chen Fang, Liu Ting, Ma Rui, Wu Rongde
Department of Pediatric Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.
Shandong Quality Inspection Center for Medical Devices, Jinan, Shandong Province, China.
J Pediatr Surg. 2017 Aug;52(8):1348-1354. doi: 10.1016/j.jpedsurg.2016.12.005. Epub 2016 Dec 20.
MiR-21 is one of the most often found miRNAs overexpressed in solid tumors, while PTEN is the most highly mutated tumor suppressor gene. Our purpose was to examine the expression levels of miR-21 and PTEN protein in Wilms' tumor (WT) and in para-tumoral tissues and to investigate the relationships among miR-21, PTEN expression, clinicopathological parameters and the prognosis of patients with WT.
The expression levels of miR-21 and PTEN protein in WT and corresponding para-tumoral tissues were investigated by qRT-PCR and Western blot, respectively. Differences in patient survival were determined using the Kaplan-Meier method and the log-rank test. A Cox proportional hazards regression analysis was used for univariate and multivariate analyses of prognostic values.
Compared with para-tumoral renal tissues, the expression levels of miR-21 were significantly upregulated in WT tissues, while the PTEN protein were significantly downregulated (P<0.05). Analyses of the clinicopathological parameters showed that the miR-21 expression level was significantly associated with age, late clinical stage, histopathological tumor type and lymphatic metastasis (P<0.05). PTEN protein expression was significantly associated with age, late clinical stage and histopathological tumor type (P<0.05). The univariate linear regression analysis illustrated a significant negative correlation between miR-21 and PTEN expression (r=-0.687, P<0.05). The Kaplan-Meier curve showed that patients with high miR-21 and low PTEN protein expression survived significantly longer (P<0.05). However, a multivariate analysis suggested that neither the expression level of miR-21 nor that of PTEN is an independent prognostic factor for overall survival.
Both upregulated miR-21 and downregulated PTEN expression have a possible correlation with the aggressive progression and poor prognosis of WT, which suggests that upregulated miR-21 and downregulated PTEN expression may be valuable markers of tumor progression and indicators of the prognosis of WT.
miR-21是实体瘤中最常被发现过表达的微小RNA之一，而PTEN是突变率最高的肿瘤抑制基因。我们的目的是检测肾母细胞瘤（WT）及瘤旁组织中miR-21和PTEN蛋白的表达水平，并研究miR-21、PTEN表达、临床病理参数与WT患者预后之间的关系。
分别采用qRT-PCR和蛋白质免疫印迹法检测WT及相应瘤旁组织中miR-21和PTEN蛋白的表达水平。采用Kaplan-Meier法和对数秩检验确定患者生存率的差异。采用Cox比例风险回归分析对预后价值进行单因素和多因素分析。
与瘤旁肾组织相比，WT组织中miR-21的表达水平显著上调，而PTEN蛋白显著下调（P<0.05）。临床病理参数分析表明，miR-21表达水平与年龄、临床晚期、组织病理学肿瘤类型及淋巴转移显著相关（P<0.05）。PTEN蛋白表达与年龄、临床晚期及组织病理学肿瘤类型显著相关（P<0.05）。单因素线性回归分析表明miR-21与PTEN表达呈显著负相关（r=-0.687，P<0.05）。Kaplan-Meier曲线显示，miR-21高表达和PTEN蛋白低表达的患者生存时间显著更长（P<0.05）。然而，多因素分析表明，miR-21和PTEN的表达水平均不是总生存的独立预后因素。
miR-21上调和PTEN表达下调均可能与WT的侵袭性进展和不良预后相关，这表明miR-21上调和PTEN表达下调可能是肿瘤进展的有价值标志物及WT预后的指标。
