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Investigation of HIF Gene Expression and Function in Gastric cancer using in silico Approaches
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Marziye Amini-Ghahfarokhi    , Maryam Kalantari-Dehaghi , Modjtaba Emadi-Baygi * |
| , emadi-m@sku.ac.ir |
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Abstract: (19 Views) |
Background and Objectives:
Hypoxia-inducible factor 1 (HIF1) is a heterodimeric transcription factor that becomes activated under hypoxic conditions and regulates the expression of genes that enable cellular adaptation to hypoxia. HIF1 plays a key role in controlling pathways related to hypoxic response, angiogenesis, epithelial–mesenchymal transition (EMT), and metastasis. This study aimed to investigate the role of HIF1 in invasion, EMT, and prognosis in gastric cancer.
Materials and Methods:
This study is a retrospective cohort computational study that was designed and conducted based on gene expression data and clinical information extracted from the TCGA database.Patients were categorized into high and low HIF1 expression groups. Differential gene expression analysis was performed using the Limma package, and univariate and multivariate Cox regression analyses were used to evaluate the association with patient survival. Weighted gene co-expression network analysis (WGCNA) was conducted to identify gene modules associated with HIF1 expression. Functional pathway enrichment was assessed using the enrichR tool. Kaplan–Meier survival analysis and ROC curve analysis were used to evaluate the prognostic impact of HIF1 expression. Nomograms combining HIF1 expression and clinical data were developed to predict patient survival.
Results:
A total of 15,060 differentially expressed genes were identified between the two HIF1 expression groups. Among the genes associated with invasion and metastasis, 10 genes—such as CD44, COL1A1, SLC12A3, and NT5E—showed significant correlation with patient survival. The royal blue module identified by WGCNA was highly correlated with HIF1 expression and was enriched in pathways including cytokine signaling, immune response, VEGF regulation, and extracellular matrix organization. Survival analysis showed that patients with high HIF1 expression had significantly shorter survival. The nomogram-based predictive models demonstrated high accuracy in predicting 3- and 5-year survival outcomes.
Conclusion:
The findings of this study indicate that HIF1 not only contributes to gastric cancer progression through pathways such as EMT, angiogenesis, metastasis, and inflammation but also serves as an independent and reliable prognostic marker. Therefore, HIF1 could be considered a potential prognostic biomarker and therapeutic target, and targeting HIF1-related pathways may open new horizons in personalized treatment of gastric cancer.
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| Keywords: Gastric cancer, HIF1, Hypoxia, Epithelial–mesenchymal transition, Survival analysis, Gene expression, Nomogram, Metastasis |
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Type of Study: Research |
Subject:
General
Received: 2025/07/18 | Revised: 2025/11/3 | Accepted: 2025/10/25
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