Digital Polymerase Chain Reaction Quantification of SERPINA1 Predicts Prognosis in High-Grade Glioma

World Neurosurg. 2018 Mar:111:e783-e789. doi: 10.1016/j.wneu.2017.12.166. Epub 2018 Jan 5.

Abstract

Background: SERPINA1 plays an anti-inflammatory role in protecting tissues from proteolytic mechanisms. SERPINA1 is positive in gliomas by immunohistochemical analysis; however, the role of SERPINA1, including the relationship with prognosis, has been uncertain. In recent years, digital polymerase chain reaction (PCR) has provided ultra-sensitive assessment of messenger RNA expression from formalin-fixed paraffin-embedded (FFPE) tissues.

Objective: In this study, we quantitatively determined the expression of SERPINA1 in high-grade gliomas (HGGs) using digital PCR, and we analyzed its relationship with prognosis.

Methods: Twenty-nine FFPE surgical samples from patients with HGGs (7 of World Health Organization [WHO] grade III and 22 of WHO grade IV), and human glioblastoma cell lines, U87 and U118, were used for analysis. A qualitative assessment using immunostaining and quantitative assessment using digital PCR were performed to assess the expression of SERPINA1.

Results: The expression of SERPINA1 was demonstrated in glioma tissues and glioblastoma multiforme cell lines by immunostaining. Digital PCR analysis showed that SERPINA1 was expressed in 14.3% and 63.6% of the tissues from patients with grade III and grade IV HGG, respectively (P = 0.035). The median overall survival of 38.8 months in the low SERPINA1 expression group was longer than that of 15.3 months in the high expression group (P = 0.030).

Conclusions: The frequency and the amount of SERPINA1 expression were higher in grade IV than in grade III HGGs. The high expression of SERPINA1 indicates a poor prognosis of HGGs.

Keywords: Digital PCR; Glioblastoma; Glioma; High-grade glioma; Prognosis; SERPINA1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / therapy
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Glioblastoma / genetics
  • Glioma / genetics*
  • Glioma / therapy
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymerase Chain Reaction / methods*
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Treatment Outcome
  • alpha 1-Antitrypsin / genetics*

Substances

  • SERPINA1 protein, human
  • alpha 1-Antitrypsin