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Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma

Edwin Cevallos Barrera, Edson Zangiacomi Martinez, Mariangela Ottoboni Brunaldi, Eduardo Antonio Donadi, Ajith Kumar Sankarankutty, Rafael Kemp and José Sebastiao dos Santos _

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Oncotarget. 2022; 13:1043-1053. https://doi.org/10.18632/oncotarget.28275

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Abstract

Edwin Cevallos Barrera1,2, Edson Zangiacomi Martinez3, Mariangela Ottoboni Brunaldi4, Eduardo Antonio Donadi5, Ajith Kumar Sankarankutty2, Rafael Kemp2 and José Sebastiao dos Santos2

1 Universidad Central del Ecuador, Ciencias Médicas, Carrera de Medicina, Hospital de Especialidades de Fuerzas Armadas HE-1, Quito, Ecuador

2 Department of Surgery and Anatomy, Ribeirao Preto Medical School, University of São Paulo, São Paulo, Brazil

3 Department of Social Medicine, Ribeirao Preto Medical School, University of São Paulo, São Paulo, Brazil

4 Department of Pathology, Ribeirao Preto Medical School, University of São Paulo, São Paulo, Brazil

5 Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, São Paulo, Brazil

Correspondence to:

José Sebastiao dos Santos, email: lab.biomol.cirugia@fmrp.usp.br

Keywords: gastric adenocarcinoma; hypoxia-induced factor; HER2; survival rate; tumor markers

Received: June 09, 2022     Accepted: August 29, 2022     Published: September 14, 2022

Copyright: © 2022 Barrera et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Since the incidence of gastric adenocarcinoma (GA) is high in populations living at high altitudes, we evaluated the influence of altitude on the expression of HIF-1 and survival of Ecuadorian GA patients. Method: 155 GA cases were studied: 56 from coastal (GAC) and 99 from mountainous regions (GAM), and 74 non-GA controls (25 coast and 49 mountain). The expression of HIF-1/HER2 was analyzed by immunohistochemistry. Analyses were performed using Fisher's exact and Breslow-Day tests for homogeneity and Kaplan-Meier curves and restricted median survival time ΔRMST. Results: HIF-1 was overexpressed in normal/inflamed gastric mucosa, especially in mountainous non-GA patients (p = 0.001). There was no difference between GAC and GAM in terms of age/gender, HIF-1/HER2 expression, stage/tumor location. Median survival at 120 months was significantly higher among GAC, with a difference (ΔRMST) of 43.7 months (95% CI 29.5, 57.8) (p < 0.001) and those with positive HIF-1 expression: ΔRMST 26.6 months (95% CI 11.0, 42.1) (p < 0.001). Positive HIF-1 expression was associated with better GAM survival, with ΔRMST 33.6 months (95% CI 14.2, 52.9) (p < 0.001). Conclusion: Despite the limitations of this retrospective study, GA patients in the coastal region and those who expressed HIF-1 exhibited a better prognosis, but this factor was associated with better survival only in the mountain region.


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