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Background <p>Glutathione peroxidases (GPxs) are a family of enzymes comprising eight members known for their peroxidase activity, which helps relieve oxidative stress by reducing hydrogen peroxide and lipid peroxides. GPxs play a crucial role in tumorigenesis, affecting DNA integrity, proliferation, cell adhesion, and survival. However, a comprehensive analysis of the expression and prognostic relevance of GPx members in gastric cancer (GC) remains underexplored.</p> Results <p>This study explored the relationship between GPx mRNA expression and prognosis in GC patients across different Lauren classifications (intestinal, diffuse, and mixed types). We found that GPx1 and GPx4 were highly expressed in all GC subtypes compared to normal tissues, while GPx7 expression was notably elevated in mixed-type GC. These findings were consistent across multiple Oncomine datasets and partially validated in TCGA GC versus normal samples. Kaplan–Meier survival analysis showed that high mRNA expression of GPx3, GPx5, GPx6, and GPx7 was associated with poor overall survival (OS) at both 5- and 10-year intervals. In contrast, elevated GPx1 expression correlated with better OS at both 5 and 10&#xa0;years. Additionally, high GPx4, GPx5, and GPx6/7 expression were linked to reduced first progression (FP), while increased GPx3, GPx4, and GPx6/7 levels were associated with shorter post-progression survival (PPS). These trends were consistent for both 5- and 10-year FP and PPS. Prognostic associations were partially validated using TCGA data. Subgroup analyses based on Lauren classification, clinicopathological features, and treatment further supported these observations.</p> Conclusions <p>This study highlights the distinct prognostic roles of GPx family members in GC. High GPx1 expression is associated with favorable outcomes, whereas elevated levels of GPx3, GPx4, GPx5, and GPx6/7 are linked to poor prognosis in GC patients, including OS, FP, and PPS. In addition to confirming previous findings, this study suggests that GPx4, GPx5, and GPx6/7 could serve as valuable prognostic markers and potential therapeutic targets in GC. Further clinical studies are needed to validate these findings and explore GPx-targeted therapies for GC.</p>

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Dual insights into gastric cancer: expression analysis and prognostic relevance of glutathione peroxidases

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月25日

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  • Biyu Zhang,
  • Denggang Fu

摘要

Background

Glutathione peroxidases (GPxs) are a family of enzymes comprising eight members known for their peroxidase activity, which helps relieve oxidative stress by reducing hydrogen peroxide and lipid peroxides. GPxs play a crucial role in tumorigenesis, affecting DNA integrity, proliferation, cell adhesion, and survival. However, a comprehensive analysis of the expression and prognostic relevance of GPx members in gastric cancer (GC) remains underexplored.

Results

This study explored the relationship between GPx mRNA expression and prognosis in GC patients across different Lauren classifications (intestinal, diffuse, and mixed types). We found that GPx1 and GPx4 were highly expressed in all GC subtypes compared to normal tissues, while GPx7 expression was notably elevated in mixed-type GC. These findings were consistent across multiple Oncomine datasets and partially validated in TCGA GC versus normal samples. Kaplan–Meier survival analysis showed that high mRNA expression of GPx3, GPx5, GPx6, and GPx7 was associated with poor overall survival (OS) at both 5- and 10-year intervals. In contrast, elevated GPx1 expression correlated with better OS at both 5 and 10 years. Additionally, high GPx4, GPx5, and GPx6/7 expression were linked to reduced first progression (FP), while increased GPx3, GPx4, and GPx6/7 levels were associated with shorter post-progression survival (PPS). These trends were consistent for both 5- and 10-year FP and PPS. Prognostic associations were partially validated using TCGA data. Subgroup analyses based on Lauren classification, clinicopathological features, and treatment further supported these observations.

Conclusions

This study highlights the distinct prognostic roles of GPx family members in GC. High GPx1 expression is associated with favorable outcomes, whereas elevated levels of GPx3, GPx4, GPx5, and GPx6/7 are linked to poor prognosis in GC patients, including OS, FP, and PPS. In addition to confirming previous findings, this study suggests that GPx4, GPx5, and GPx6/7 could serve as valuable prognostic markers and potential therapeutic targets in GC. Further clinical studies are needed to validate these findings and explore GPx-targeted therapies for GC.