A 3-miRNA Signature Enables Risk Stratification in Glioblastoma Multiforme Patients with Different Clinical Outcomes

Curr Oncol. 2022 Jun 16;29(6):4315-4331. doi: 10.3390/curroncol29060345.

Abstract

Malignant gliomas constitute a complex disease phenotype that demands optimum decision-making as they are highly heterogeneous. Such inter-individual variability also renders optimum patient stratification extremely difficult. microRNA (hsa-miR-20a, hsa-miR-21, hsa-miR-21) expression levels were determined by RT-qPCR, upon FFPE tissue sample collection of glioblastoma multiforme patients (n = 37). In silico validation was then performed through discriminant analysis. Immunohistochemistry images from biopsy material were utilized by a hybrid deep learning system to further cross validate the distinctive capability of patient risk groups. Our standard-of-care treated patient cohort demonstrates no age- or sex- dependence. The expression values of the 3-miRNA signature between the low- (OS > 12 months) and high-risk (OS < 12 months) groups yield a p-value of <0.0001, enabling risk stratification. Risk stratification is validated by a. our random forest model that efficiently classifies (AUC = 97%) patients into two risk groups (low- vs. high-risk) by learning their 3-miRNA expression values, and b. our deep learning scheme, which recognizes those patterns that differentiate the images in question. Molecular-clinical correlations were drawn to classify low- (OS > 12 months) vs. high-risk (OS < 12 months) glioblastoma multiforme patients. Our 3-microRNA signature (hsa-miR-20a, hsa-miR-21, hsa-miR-10a) may further empower glioblastoma multiforme prognostic evaluation in clinical practice and enrich drug repurposing pipelines.

Keywords: 3-microRNA signature; glioblastoma multiforme; image classification; machine learning; pattern recognition; risk stratification.

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Prognosis
  • Risk Assessment

Substances

  • MicroRNAs