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

Angiotensinogen rs5050 Germline Genetic Variant as Potential Biomarker of Poor Prognosis in Astrocytoma

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Free PMC article

Angiotensinogen rs5050 Germline Genetic Variant as Potential Biomarker of Poor Prognosis in Astrocytoma

Alexander Perdomo-Pantoja et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Kaplan-Meier survival estimates.
(A) Survival analysis of the AGT rs5050 genotypes (TT in green, TG in orange, and GG in red) separately, showing the shorter survival in GG-genotype patients (p = .05). (B) Comparing GG-genotype against TT + TG-genotypes of AGT rs5050, patients harboring GG-genotype (in red) exhibited lower survival rates compared to TT + TG (in green) genotypes patients (2 vs. 11.5 months [p = .01]).
Fig 2
Fig 2. Hypothetical dual mechanism of the AGT rs5050 genetic variant.
The 5´ upstream core promoter region of the human AGT gene, where rs5050 is identified, has been recognized as an authentic regulator for the transcription of AGT mRNA [38]. Differences in the AGT plasma levels were found between the genotypes of rs5050, with the GG-genotype associated with the lowest levels [22]. AGT expresses opposite effects, showing an antiangiogenic property, such as some Serpins family members, and a proangiogenic activity as the precursor of AngII. It might depend upon local conditions that define which of the effects dominates [48].

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Grant support

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