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. 2022 Sep 14:13:1043-1053.
doi: 10.18632/oncotarget.28275. eCollection 2022.

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

Edwin Cevallos Barrera  1   2 , Edson Zangiacomi Martinez  3 , Mariangela Ottoboni Brunaldi  4 , Eduardo Antonio Donadi  5 , Ajith Kumar Sankarankutty  2 , Rafael Kemp  2 , José Sebastiao Dos Santos  2
Affiliations

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

Edwin Cevallos Barrera et al. Oncotarget. .

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST Authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Illustrative HER2 immunohistochemistry labeling observed for gastric adenocarcinoma (GA) patients at 400× magnification.
(A) Lack of labelling (score 0), (B) Weak labelling (arrows; score 1), (C) Weak to moderate staining (score 2), and (D) Strong membrane labelling (arrows; score 3).
Figure 2
Figure 2. Illustrative HIF-1 immunohistochemistry labeling observed at 400× magnification for gastric samples.
(A) Gastric mucosa without gastric adenocarcinoma (GA) (score 8), (B) Lack of labelling in a GA patient (score 0), (C) Moderate expression observed in more than 75% of the nuclei (score 8), and (D) Strong labelling observed in more than 75% of the nuclei (score 12).
Figure 3
Figure 3. Overall survival of gastric adenocarcinoma (GA) patients.
(A) All studied patients (n = 155), and of GA patients stratified by gender (B), age (C), coastal or mountainous regions (D), expression of HIF-1 (E), and expression of HER2 (F).
Figure 4
Figure 4
Survival rate of Ecuadorian gastric adenocarcinoma patients from coastal or mountainous regions, stratified by gender (A), Age (B), Expression of HIF-1 (C), and expression of HER2 (D).
See this image and copyright information in PMC

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