Clinicopathological parameters and prognostic relevance of miR-21 and PTEN expression in Wilms' tumor

J Pediatr Surg. 2017 Aug;52(8):1348-1354. doi: 10.1016/j.jpedsurg.2016.12.005. Epub 2016 Dec 20.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: PTEN; Wilms' tumor; miR-21.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Child, Preschool
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Infant
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Male
  • MicroRNAs
  • PTEN Phosphohydrolase / biosynthesis
  • PTEN Phosphohydrolase / genetics*
  • Prognosis
  • RNA, Neoplasm / genetics*
  • Real-Time Polymerase Chain Reaction
  • Tumor Suppressor Proteins
  • Wilms Tumor / diagnosis
  • Wilms Tumor / genetics*
  • Wilms Tumor / metabolism

Substances

  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • Tumor Suppressor Proteins
  • PTEN Phosphohydrolase
  • PTEN protein, human