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

PLoS One. 2018 Nov 1;13(11):e0206590. doi: 10.1371/journal.pone.0206590. eCollection 2018.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Angiotensinogen / blood
  • Angiotensinogen / genetics*
  • Astrocytoma / diagnosis*
  • Astrocytoma / genetics*
  • Astrocytoma / mortality
  • Astrocytoma / therapy
  • Biomarkers, Tumor / genetics
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Pilot Projects
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Angiotensinogen

Grants and funding

This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACYT) (México) (Salud-2013-01-202720).