Influence of high altitude on the expression of HIF-1 and on the prognosis of Ecuadorian patients with gastric adenocarcinoma
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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
|José Sebastiao dos Santos,||email:||[email protected]|
Keywords: gastric adenocarcinoma; hypoxia-induced factor; HER2; survival rate; tumor markers
Received: June 09, 2022 Accepted: August 29, 2022 Published: September 14, 2022
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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