PLoS ONE (Jan 2018)

Angiotensinogen rs5050 germline genetic variant as potential biomarker of poor prognosis in astrocytoma.

  • Alexander Perdomo-Pantoja,
  • Sonia Iliana Mejía-Pérez,
  • Nancy Reynoso-Noverón,
  • Liliana Gómez-Flores-Ramos,
  • Ernesto Soto-Reyes,
  • Thalía Estefania Sánchez-Correa,
  • Lissania Guerra-Calderas,
  • Clementina Castro-Hernandez,
  • Silvia Vidal-Millán,
  • José Sánchez-Corona,
  • Lucia Taja-Chayeb,
  • Olga Gutiérrez,
  • Bernardo Cacho-Diaz,
  • Rosa Maria Alvarez-Gomez,
  • Juan Luis Gómez-Amador,
  • Patricia Ostrosky-Wegman,
  • Teresa Corona,
  • Luis Alonso Herrera-Montalvo,
  • Talia Wegman-Ostrosky

DOI
https://doi.org/10.1371/journal.pone.0206590
Journal volume & issue
Vol. 13, no. 11
p. e0206590

Abstract

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INTRODUCTION:Renin-angiotensin system (RAS) in brain cancer represents a scarcely explored field in neuro-oncology. Recently, some pre- and clinical studies have reported that RAS components play a relevant role in the development and behavior of gliomas. The angiotensinogen (AGT) rs5050 genetic variant has been identified as a crucial regulator of the transcription of AGT mRNA, which makes it a logical and promising target of research. The aim of this study was to determine the relationship between the AGT rs5050 genetic variant in blood with prognosis in astrocytoma. METHODS:A prospective pilot study was performed on forty-eight astrocytoma patients, who received the standard-of-care treatment. Blood samples were taken prior to surgery and DNA was sequenced using Ion Torrent next-generation sequencing and analyzed by Ion Reporter software. Descriptive, bivariate, multivariate, and survival analyses were performed using SPSS v21, STATA 12 and GraphPad Prism 7. RESULTS:Median follow-up was 41 months (range 1-48). Survival analysis showed a significant difference between the rs5050 genotypes (p = .05). We found lower survival rates in individuals with the GG-genotype of rs5050 AGT compared to patients with the TT- and TG-genotype (2 months vs. 11.5 months, respectively [p = .01]). In bivariate and multivariate analyses, GG-genotype was negatively associated with survival. CONCLUSIONS:In patients with astrocytoma, AGT rs5050 GG-genotype was associated with poor prognosis. We propose this germline genetic variant as a complementary biomarker, which can be detected practically and safely in blood samples or saliva.