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ARHGAP11A Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

ABSTRACT: Background: ARHGAP11A, belongs to RhoGAPs family, is vital for cell motility. However, the role of ARHGAP11A in gastric cancer is obscure. Methods: The expression level of ARHGAP11A was analyzed by Oncomine database. The correlation of ARHGAP11A expression with immune infiltrates and associated gene markers was clarified by Tumor IMmune Estimation Resource and Gene Expression Profiling Interactive Analysis database. The correlation between ARHGAP11A expression and the patient prognosis was identified by Kaplan-Meier plotter and PrognoScan. Genetic changes of ARHGAP11A were analyzed by cBioPortal. The protein-protein interaction network and gene functional enrichment analysis were constructed and performed by GeneMANIA and Metascape. Results: We found that the expression levels of ARHGAP11A were elevated in various cancers including gastric cancer when compared with normal tissues. High expression of ARHGAP11A was significantly correlated with a better prognosis in gastric cancer. We revealed that the expression of ARHGAP11A was negatively associated with infiltration levels of CD8+ T cells, CD4+ T cells, macrophages and dendritic cells. In addition, ARHGAP11A expression was significantly correlated with gene markers of these immune cells. Lastly, gene functional enrichment analysis indicated that ARHGAP11A involved in regulating lymphocyte activation, cell division, cell killing, myeloid leukocyte differentiation and leukocyte apoptosis. Conclusion: Our findings demonstrated that ARHGAP11A was a valuable prognostic biomarker in gastric cancer. Further work is needed to validate its role and underlying mechanisms in regulating immune infiltrates.

SUBMITTER: Fan B

PROVIDER: S-EPMC8558302 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeThe serine protease inhibitor clade E member 1 (SERPINE1) has been studied as a potential biomarker in a variety of cancers, but poorly studied in gastric cancer (GC). The purpose of this study was to explore the prognostic value of SERPINE1 in GC and primarily analyze its functions.MethodsWe analyzed the the prognostic value of SERPINE1 and studied the relationship with clinicopathologic biomarkers in gastric cancer. The expression of SERPINE1 was analyzed by GEO and TCGA databases. Moreover, we validated the results by immunohistochemistry. Next, the correlation analysis between SERPINE1 and the cuproptosis-related genes was analyzed by the "Spearman" method. CIBERSORT and TIMER algorithms were used to analyze the correlation of SERPINE1 with immune infiltration. Furthermore, GO and KEGG gene enrichment analyses were used to study the functions and pathways that SERPINE1 might be involved in. Then, drug sensitivity analysis was performed using CellMiner database. Finally, a cuproptosis-immune-related prognostic model was constructed using genes related to immune and cuproptosis, and verified against external datasets.ResultsSERPINE1 was up-regulated in gastric cancer tissues, which tends toward poor prognosis. Using immunohistochemistry experiment, the expression and prognostic value of SERPINE1 were verified. Then, we found that SERPINE1 was negatively correlated with cuproptosis-related genes FDX1, LIAS, LIPT1, and PDHA1. On the contrary, SERPINE1 was positively correlated with APOE. This indicates the effect of SERPINE1 on the cuproptosis process. Furthermore, by conducting immune-related analyses, it was revealed that SERPINE1 may promote the inhibitory immune microenvironment. The infiltration level of resting NK cells, neutrophils, activated mast cells, and macrophages M2 was positively correlated with SERPINE1. However, B cell memory and plasma cells were negatively correlated with SERPINE1. Functional analysis showed that SERPINE1 was closely related to angiogenesis, apoptosis, and ECM degradation. The KEGG pathway analysis showed that SERPINE1 may be associated with P53, Pi3k/Akt, TGF-β, and other signaling pathways. Drug sensitivity analysis showed that SERPINE1 could be also seen as a potential treatment target. The risk model based on SERPINE1 co-expression genes could better predict the survival of GC patients than SERPINE1 alone. We also verified the prognostic value of the risk score by GEO external datasets.ConclusionSERPINE1 is highly expressed in gastric cancer and related to poor prognosis. SERPINE1 may regulate cuproptosis and the immune microenvironment by a series of pathways. Therefore, SERPINE1 as a prognostic biomarker and potential therapeutic target deserves further study.

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ARHGAP11A Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric Cancer

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