Comparing tumor microRNA profiles of patients with long‑ and short‑term‑surviving glioblastoma

Abstract

Glioblastoma is one of the most frequent primary brain tumors with a poor prognosis. Nevertheless, some patients show a prolonged survival. The aim of the present study was to compare the expression profiles of tumor derived microRNA (miR) of long‑term survivors with those of short‑term survivors in order to identify differentially expressed miRs as well as their target genes, which may elucidate mechanisms that play a role in varying tumor progression and, therefore, may influence survival. Formalin‑fixed paraffin‑embedded samples of 23 patients with glioblastoma were classified according to overall survival. Profiles of miR expression were determined using Nanostring technology. Expression levels of potential target genes of differentially expressed miRs were assessed using immunohistochemistry. MiR profiles of long‑term survivors differed from those of short‑term survivors. A total of three prominent differentially expressed miRs were highlighted: MiR‑130b‑3p, which is downregulated in long‑term survivors, and miR‑146b‑5p and miR‑148a‑3p, which are upregulated in long‑term survivors. Known tumor suppressor genes are among targets potentially affected by miR‑130b‑3p, whereas targets of miR‑146b‑5p and miR‑148a‑3p consist of several genes known to have a role in tumor invasion and aggressiveness. In conclusion, it was revealed that a type of miR‑signature was associated with short‑ and long‑term survival, potentially serving as biomarker for disease progression and providing a base for further functional studies.

Keywords: expression profile; glioblastoma; microRNAs; molecular signature; overall survival.

Figure 1.

Boxplot representation of normalized expression values of miR-130b-3p, miR-146b-5p and miR-148a-3p, comparing LTS and STS groups. Center lines indicate medians, box limits indicate the 25 and 75th percentiles, whiskers extend 1.5× interquartile range from percentiles and dots represent outliers (generated using BoxPlotR; http://shiny.chemgrid.org/boxplotr/). *P<0.05. miR, microRNA; STS, short-term survivor; LTS, long-term survivor.

Figure 2.

Visualization of the signature model miR-130b-3p low, miR-146b-5p high, miR-148a-3p high or vice versa. Each column represents a patient, and the number indicates for how many of the three miRs the model statement is true. Blue=long-term survivor; yellow=short-term survivor; green=low expression; red=high expression. miR, microRNA.

Figure 3.

PTEN immunohistochemistry, sorted, from left to right, in an ascending order of miR-130b-3p counts days in patients #1 to 23. miR, microRNA; OS, overall survival; STS, short-term survivor; LTS, long-term survivor; d, days.

Figure 4.

TRAF6 immunohistochemistry, sorted, from left to right, in an ascending order of miR-146b-5p counts in patients #1 to 23. miR, microRNA; OS, overall survival; STS, short-term survivor; LTS, long-term survivor; d, days; TRAF6, TNF receptor-associated factor 6.