A SEMA3 Signaling Pathway-Based Multi-Biomarker for Prediction of Glioma Patient Survival

Int J Mol Sci. 2020 Oct 7;21(19):7396. doi: 10.3390/ijms21197396.

Abstract

Glioma is a lethal central nervous system tumor with poor patient survival prognosis. Because of the molecular heterogeneity, it is a challenge to precisely determine the type of the tumor and to choose the most effective treatment. Therefore, novel biomarkers are essential to improve the diagnosis and prognosis of glioma tumors. Class 3 semaphorin proteins (SEMA3) play an important role in tumor biology. SEMA3 transduce their signals by using neuropilin and plexin receptors, which functionally interact with the vascular endothelial growth factor-mediated signaling pathways. Therefore, the aim of this study was to explore the potential of SEMA3 signaling molecules for prognosis of glioma patient survival. The quantitative real-time PCR method was used to evaluate mRNA expression of SEMA3(A-G), neuropilins (NRP1 and NRP2), plexins (PLXNA2 and PLXND1), cadherins (CDH1 and CDH2), integrins (ITGB1, ITGB3, ITGA5, and ITGAV), VEGFA and KDR genes in 59 II-IV grade glioma tissues. Seven genes significantly associated with patient overall survival were used for multi-biomarker construction, which showed 64%, 75%, and 68% of accuracy of predicting the survival of 1-, 2-, and 3-year glioma patients, respectively. The results suggest that the seven-gene signature could serve as a novel multi-biomarker for more accurate prognosis of a glioma patient's outcome.

Keywords: Glioma; SEMA3; VEGF; biomarker; gene expression; glioblastoma; neuropilin; patient survival; plexin; semaphoring.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Astrocytoma / etiology
  • Astrocytoma / metabolism
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • Biomarkers*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / etiology
  • Glioma / metabolism*
  • Glioma / mortality*
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Prognosis
  • ROC Curve
  • Semaphorin-3A / metabolism*
  • Signal Transduction*

Substances

  • Biomarkers
  • Semaphorin-3A