Increased ANXA5 expression in stomach adenocarcinoma infers a poor prognosis and high level of immune infiltration

Su, Zhaoran; Shu, Kuanshan; Li, Guangyao

doi:10.3233/cbm-210482

Cited by 11 publications

(8 citation statements)

References 28 publications

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“…The increased expression of ANXA5 was associated with a worse prognosis in GC patients, promoting GC by affecting extracellular matrix-related processes and immune infiltration. [28] CCN1 can induce the migration and invasion of GC cells by activating the integrin/nuclear factor-κB/cyclooxygenase-2 signaling pathway, [29][30][31] and it is also a metastatic marker of gastric cardia adenocarcinoma. [32] EGF-positive GC patients have a worse prognosis than EGF-negative GC patients.…”

Section: Discussionmentioning

confidence: 99%

ANRGs impact on gastric cancer progression and drug efficacy: A comprehensive study

Zhang,

Zhu

2023

Medicine

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Gastric cancer (GC) is a significant contributor to cancer-related mortality globally, with the heterogeneity of metastasis and treatment impacting patient prognosis. Currently, the treatment of GC still relies on early surgical resection, and comprehensive treatment is needed for patients with metastatic GC. Anikis-related genes (ANRGs) have been shown to affect tumor metastasis. Exploring the role of ANRGs in GC will help us understand the mechanism of tumor metastasis; screening precise targets and selecting appropriate chemotherapeutics will help individualize the treatment of GC patients. In this study, we established a prognostic scoring model based on ANRGs and explored their association with GC patient prognosis, immune microenvironment, chemotherapeutic drug sensitivity, and small molecule compounds. Our findings revealed that a gene signature composed of ANXA5, CCN1, EGF, VTN, and ZBTB7A accurately predicted GC patient prognosis. Patients in the low-risk group had better outcomes, higher macrophage M1 infiltration, and higher tumor mutation burden. The half maximal inhibitory concentration (IC50) values of Ponatinib (ap.24534), Motesanib (amg.706), and Navitoclax (abt.263) were lower in the high-risk group, indicating that patients in the high-risk group were more sensitive to these chemotherapy drugs, meaning with better clinical outcomes. In addition, we screened the small molecule compound SGC-CBP30 that can inhibit ANXA5 and CCN1, and these results help individualized treatment of GC patients. Our study identified key genes based on ANRGs and developed a novel gene signature for predicting the prognosis of GC patients and understanding the relationship between immunity and tumor mutation burden. Additionally, we identified chemotherapeutic drugs that can guide GC treatment and elucidated the binding affinity between specific targeted drugs and distinct protein sites, providing novel insights for the precise treatment of GC patients.

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Section: Discussionmentioning

confidence: 99%

ANRGs impact on gastric cancer progression and drug efficacy: A comprehensive study

Zhang,

Zhu

2023

Medicine

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“…Although the relationship between ANXA9 and immune infiltration has not been well studied, the relationship between other ANXA family members and immune infiltration has been extensively reported. For example, ANXA1 promotes the suppressive functions of Tregs in triple-negative breast cancer [ 7 ], ANXA2 acts as a potential marker of immunosuppression in glioma [ 25 ], and ANXA5 expression in stomach adenocarcinoma is significantly correlated with various infiltrating immune cells [ 26 ]. These suggest that ANXA9, as a member of ANXA family, may affect the immune response in CRC, but the effects of ANXA9 in regulating immune-infiltrating cells requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Annexin A9 promotes cell proliferation by regulating the Wnt signaling pathway in colorectal cancer

Mao

et al. 2023

Human Cell

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Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Expression of Annexin A9 (ANXA9), a member of the annexin A family, is upregulated in CRC. However, the molecular role of ANXA9 in CRC remains unknown. In the present study, we aimed to investigate the function of ANXA9 and to elucidate the mechanisms underlying its regulation in CRC. In this study, mRNA expression data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and GEPIA database, respectively. Kaplan–Meier analysis was used to analyze the survival rates. LinkedOmics and Metascape databases were used to explore the potential mechanisms of regulation of ANXA9 and to identify genes co-expressed with ANXA9. Finally, in vitro experiments were used to evaluate the function of ANXA9 and explore potential mechanisms. We found that ANXA9 expression was significantly elevated in CRC tissue and cells. High ANXA9 expression was associated with shorter overall survival, poorer disease specific survival, as well as with patient age, clinical stage, M stage, and OS events in CRC. Knockdown of ANXA9 inhibited cell proliferation, invasion, migratory potential, and cell cycle arrest. Mechanistically, functional analysis revealed that genes co-expressed with ANXA9 were mainly enriched in the Wnt signaling pathway. ANXA9 deletion suppressed cell proliferation via the Wnt signaling pathway, while Wnt activation reversed the effects of ANXA9. In conclusion, ANXA9 may promote CRC progression by regulating the Wnt signaling pathway and may be a potential diagnostic biomarker in the clinical management of CRC.

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“…Xiantao is a comprehensive bioinformatics tool ( (accessed on 20 June 2022) based on R language that has realized online analysis and visualization through front–end technology to conduct analysis of public database data [ 13 ]. We first applied this tool to The Cancer Genome Atlas (TCGA, (accessed on 20 June 2022)) and the Genotype-Tissue Expression (GTEx, gtexportal.org/home/ (accessed on 20 June 2022)) databases to analyze the mRNA levels of SEC23A in 33 cancer entities.…”

Section: Methodsmentioning

confidence: 99%

Increased SEC23A Expression Correlates with Poor Prognosis and Immune Infiltration in Stomach Adenocarcinoma

Linnebacher

2023

Cancers

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Background: Previous studies have described that the SEC23A gene is involved in the occurrence and development of various tumor entities. However, little is known about its expression and relevance in stomach adenocarcinoma (STAD). The aim of this study was to bioinformatically analyze the role of SEC23A in STAD, followed by patient tissue sample analyses. Materials and methods: SEC23A expression levels in STAD and normal gastric tissues were analyzed in the Cancer Genome Atlas and Gene Expression Omnibus databases; results were verified in fresh clinical STAD specimens on both gene and protein expression levels. SEC23A expression correlated with survival parameters by Kaplan–Meier and multivariate Cox regression analyses. The top genes co-expressed with SEC23A were identified by gene set enrichment analysis (GSEA) using the clusterProfiler package in R. Furthermore, the R package (immunedeconv), integrating the CIBERSORT algorithm, was used to estimate immune cell infiltration levels in STAD. Results: SEC23A gene and sec23a protein expression were both significantly upregulated in STAD, and this correlated with the pT stage. Moreover, high SEC23A expression was associated with poor disease-free and overall survival of STAD patients. Cox analyses revealed that besides age and pathologic stage, SEC23A expression is an independent risk factor for STAD. GSEA indicated that SEC23A was positively associated with ECM-related pathways. In the CIBERSORT analysis, the level of SEC23A negatively correlated with various infiltrating immune cell subsets, including follicular helper T cells, Tregs, activated NK cells and myeloid dendritic cells. Finally, the expression levels of immune checkpoint-related genes, including HAVCR2 and PDCD1LG2, were significantly increased in the high SEC23A expression group. Conclusions: We observed the significantly upregulated expression of SEC23A in STAD, an association with disease progression, patients’ prognosis and infiltrating immune cell subsets. Thus, we propose SEC23A as an independent prognostic factor with a putative role in immune response regulation in STAD.

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Increased ANXA5 expression in stomach adenocarcinoma infers a poor prognosis and high level of immune infiltration

Cited by 11 publications

References 28 publications

ANRGs impact on gastric cancer progression and drug efficacy: A comprehensive study

ANRGs impact on gastric cancer progression and drug efficacy: A comprehensive study

Annexin A9 promotes cell proliferation by regulating the Wnt signaling pathway in colorectal cancer

Increased SEC23A Expression Correlates with Poor Prognosis and Immune Infiltration in Stomach Adenocarcinoma

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