Dataset Information

ANTXR1 Is a Prognostic Biomarker and Correlates With Stromal and Immune Cell Infiltration in Gastric Cancer.

ABSTRACT: Gastric cancer (GC) is a complex and heterogeneous disease, making it difficult to ascertain the optimal therapeutic approach for individual GC patients. Stromal and immune cell infiltration in GC has a strong correlation with clinical outcomes; however, the underlying mechanisms that drive immunosuppression remain vastly undiscovered. Recent studies validated that anthrax toxin receptor 1 (ANTXR1) is aberrantly expressed in several cancers and holds promise as a new therapeutic target for cancer. However, its immunological roles in GC are still unclear. Here, we show that we identify the distinct stromal and immune cell infiltration in GC between the high and low ANTXR1 expression group by analyzing genomic data. Clinically, ANTXR1 is highly expressed in GC and correlates with adverse clinicopathological characteristics. Additionally, high ANTXR1 expression is linked to markedly poor clinical outcomes and resistance to chemotherapy, whereas the low ANTXR1 expression group is correlated with better outcomes and response to chemotherapy in GC patients. We further revealed the differential landscape of somatic tumor mutation burden (TMB) between the two groups and observed that patients with high ANTXR1 expression suffered from a lower TMB, potentially leading to less sensitivity to checkpoint therapy. Molecularly, results displayed that ANTXR1 is an immunosuppressive element, which may perform its function via promoting the secretion of immunosuppressive factors that play a significant role in modulating tumor-associated fibroblast transformation, M2 macrophage polarization, and T cell exhaustion. Gene set enrichment analysis revealed that cancer-related pathways including epithelial-to-mesenchymal transition, focal adhesion, and transforming growth factor-? (TGF-?) signaling pathways were enriched in high ANTXR1 expression tumors. Our work suggests that ANTXR1 could not only serve as a valuable prognostic biomarker in GC but also be deemed as a potential immunotherapeutic target and useful biomarker of sensitivity to chemotherapy.

SUBMITTER: Huang X

PROVIDER: S-EPMC7770144 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ANTXR1 Is a Prognostic Biomarker and Correlates With Stromal and Immune Cell Infiltration in Gastric Cancer.

Huang Xiaodong X Zhang Jie J Zheng Yongbin Y

Frontiers in molecular biosciences 20201215

Gastric cancer (GC) is a complex and heterogeneous disease, making it difficult to ascertain the optimal therapeutic approach for individual GC patients. Stromal and immune cell infiltration in GC has a strong correlation with clinical outcomes; however, the underlying mechanisms that drive immunosuppression remain vastly undiscovered. Recent studies validated that anthrax toxin receptor 1 (ANTXR1) is aberrantly expressed in several cancers and holds promise as a new therapeutic target for cance ...[more]

PMID: 33385012

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Project description:BackgroundHsa_circ_0072309 has been identified as a tumor suppressor in several carcinomas. However, its precise role in gastric cancer (GC) remains largely unknown. This study was aimed to explore the precise role of Hsa_circ_0072309 in GC.MethodsThe transcriptional and clinical data of stomach adenocarcinoma were downloaded using the University of California SantaCruz (UCSC) Xena browser. The circular RNA (circRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database. The expression profile and survival analysis of differentially expressed micro RNAs (DEMIs) and differentially expressed messenger RNAs (DEMs) were performed. Correlations between the expression and immune infiltration of the DEMS were studied. Additionally, the expression of hsa_circ_0072309 in GC tissues and cell lines were validated, and the relationship between its expression and clinical features was investigated. Gain- and loss-of function experiments and molecular interaction experiments were also conducted.ResultsOverall, 7 differentially expressed circRNAs, 13 DEMIs, and 17 DEMs were screened. Two DEMIs (hsa_miR-34a-3p and hsa_miR-326) and five DEMs (C7, MARCKSL1, UBE2T, OLR1, and HOXC11) showed significant differences in the high- and low-risk groups. The most significantly enriched Gene Ontology terms were the circadian regulation of gene expression and protein binding. The most significantly enriched Kyoto Encyclopedia of Genes and Genomes pathways were the PI3K-Akt and Ras signal pathways. Additionally, six genes were significantly correlated with immune infiltration. The real-time quantitative PCR (RT-qPCR) results revealed a significant downregulation of hsa_circ_0072309 in GC tissues related to tumor size, vascular invasion, and lymph node metastasis. A hsa_circ_0072309 overexpression suppressed whereas a hsa_circ_0072309 knockdown promoted GC cells proliferation and migration in vitro; in addition, hsa_circ_0072309 could directly bind to has-miR-34a-3p and has-miR-330-5p.ConclusionsHsa_circ_0072309 is a potential diagnostic biomarker for GC, and complement component 7 may be a tumor suppressor. These may potentially predict the prognosis of patients with GC and may become new therapeutic targets.

Project description:BackgroundProtein phosphatase magnesium-dependent 1 delta (PPM1D), also referred to as wild-type p53-induced phosphatase 1 (Wip1) or protein phosphatase 2C delta (PP2Cδ), is an oncogenic nuclear serine/threonine phosphatase belonging to the PP2C family. However, the knowledge regarding PPM1D mRNA expression, tumor immunity, and the prognosis in hepatocellular carcinoma (HCC) is scanty.MethodsWe analyzed PPM1D, including its expression in both the normal and tumor tissue using the Sangerbox database and Tumor Immune Estimation Resource (TIMER). We evaluated its correlation with prognosis in different tumor types by the Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between PPM1D and the cancer immune infiltrates were determined using TIMER. The correlations between PPM1D expression and gene marker sets of the immune infiltrates were established by both the TIMER and GEPIA. Immunohistochemistry was performed to detect the expression of Wip1 protein encoded by PPM1D in HCC, and the relationship between Wip1 expression and the prognosis of HCC were analyzed.ResultsWe found out that PPM1D mRNA expression was significantly higher in several human cancers, including HCC, than in the corresponding normal human tissues. The PPM1D mRNA high expression in HCC was significantly correlated with poor prognosis. The expression was associated with progression-free survival (PFS) in multiple HCC patients' cohorts (PFS HR = 1.5, P = 0.0066). This was especially in early stage (stage 1) and AJCC_T 1 of HCC. Besides, PPM1D mRNA expression indicated a positive correlation with tumor-infiltrating Monocytes, tumor-associated macrophages (TAMs), M1 Macrophage, M2 Macrophage, dendritic cells (DCs), T-helper (Th) and Treg. Wip1 was higher in HCC than paracancerous tissue. High expression of Wip1 was associated with poor prognosis of HCC.ConclusionOur findings suggested that PPM1D mRNA is critical in activating tumor immunity. Besides, they implied that PPM1D could be a potential prognostic biomarker for cancer progression. Moreover, it correlated with tumor immune cell infiltration in HCC.

Dataset Information

ANTXR1 Is a Prognostic Biomarker and Correlates With Stromal and Immune Cell Infiltration in Gastric Cancer.

Publications

ANTXR1 Is a Prognostic Biomarker and Correlates With Stromal and Immune Cell Infiltration in Gastric Cancer.

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