Therapy-, gender- and race-specific microRNA markers, target genes and networks related to glioblastoma recurrence and survival

Abstract

Aim: To identify and study targets of microRNA biomarkers of glioblastoma survival across events (death and recurrence) and phases (life expectancy or post-diagnostic) using functional and network analyses.

Materials and methods: microRNAs associated with glioblastoma survival within and across race, gender, recurrence, and therapy cohorts were identified using 253 individuals, 534 microRNAs, Cox survival model, cross-validation, discriminant analyses, and cross-study comparison.

Results: All 45 microRNAs revealed as being associated with survival were confirmed in independent cancer studies and 25 in glioblastoma studies. Thirty-nine and six microRNAs (including hsa-miR-222) were associated with one and multiple glioblastoma survival indicators, respectively. Nineteen and 26 microRNAs exhibited cohort-dependent (including hsa-miR-10b with therapy and hsa-miR-486 with race) and independent associations with glioblastoma, respectively.

Conclusion: Sensory perception and G protein-coupled receptor processes were enriched among microRNA gene targets also associated with survival and network visualization highlighted their relations. These findings can help to improve prognostic tools and personalized treatments.

Figure 1

Overall survival plots for males (black lines) and females (gray lines) that have high (dash lines) and low (solid line) levels of ebv-miR-bhrf1-1.

Figure 2

Network of target genes of glioblastoma microRNAs. Footnote. Circular pink nodes denote target genes of microRNAs associated with glioblastoma survival that also have a significant association with survival themselves. Square gray nodes denote a maximum of one intermediate gene between target genes. Edges denote known relationship between genes from several databases and summarized in the SysBiomics repository.