Background: We successfully screened the important interacting protein peroxiredoxin 4 (PRDX4) of thioredoxin domain-containing protein 5 (TXNDC5) in gastric cancer. However, its specific molecular mechanism in gastric cancer remains unclear. This study aimed to verify the interaction between PRDX4 and TXNDC5 protein molecules in gastric cancer and analyze the expression and functional significance of PRDX4 in gastric cancer using bioinformatics methods.
Methods: The interaction between TXNDC5 and PRDX4 was verified by the coimmunoprecipitation (co-IP) of the total protein of gastric cancer cells, and tissues with high expressions of TXNDC5. The Human Protein Atlas (HPA) database, UCSC Xena (University of California Santa Cruz xenabrowser) platform, the Kaplan-Meier Plotter platform, and the TIMER (Tumor IMmune Estimation Resource) platform were used to analyze the expression and subcellular localization of the PRDX4 molecule in normal human gastric tissue, the difference in expression between gastric cancer tissue and normal gastric tissue, the relationship between the expression of PRDX4 and survival, its functional significance in gastric cancer cells, and its effect on the tumor immune microenvironment (TIME).
Results: The data analysis results showed that the expression of PRDX4 messenger RNA (mRNA) in the gastric cancer tissues was significantly higher than that in the normal tissues (P<0.05). PRDX4 could affect the occurrence and development of tumors by participating in the neutrophil degranulation signaling pathway to regulate tumor immunity. The expression level of PRDX4 has a certain relationship with the TIME; that is, it is mainly negatively correlated with the infiltration of B lymphocytes and CD4+ T lymphocytes (P<0.05). The expression level of PRDX4 was positively correlated with the expression of LILRB2 (leukocyte immunoglobulin-like receptor subfamily B member 2), and negatively correlated with BLTA (B and T lymphocyte attenuation factor) and VISTA (V-type immunoglobulin domain-containing suppressor of T cell activation) (P<0.05).
Conclusions: There is an interaction between PRDX4 and TXNDC5 protein molecules in gastric cancer. PRDX4 gene expression is significantly up-regulated in gastric cancer. It may reduce the infiltration of B lymphocytes and CD4+ T lymphocytes and affect the expression of LILRB2, BLTA, and VISTA immune checkpoints, leading to anti-tumor immunosuppression.
Keywords: PRDX4 gene; gastric cancer; molecular signaling pathways; survival curve; tumor immune microenvironment (TIME).
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