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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

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


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.


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