Identification of TYROBP and C1QB as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis

Jiang, Junjie; Ding, Yongfeng; Wu, Mengjie; Lyu, Xiadong; Wang, Haifeng; Chen, Yanyan; Wang, Haiyong; Teng, Lisong

doi:10.3389/fonc.2020.01765

Cited by 32 publications

(28 citation statements)

References 63 publications

(78 reference statements)

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“…Functionally, TYROBP encodes a transmembrane signaling polypeptide on the surface of a variety of immune cells that contains an immunoreceptor tyrosine-based activation motif in its cytoplasmic domain and mediates signaling transductions (Dietrich et al, 2000;Shabo et al, 2013;Töpfer et al, 2015). It has been reported that TYROBP expression is associated with CD8 T cell infiltration in gastric cancer and clear cell renal cell carcinoma (Jiang et al, 2020;Wu et al, 2020). In line with these pieces of evidence, our result showed that TYROBP expression is positively correlated with CD8 T cell infiltration in the osteosarcoma tumor microenvironment.…”

Section: Discussionsupporting

confidence: 83%

Classification of Osteosarcoma Based on Immunogenomic Profiling

Wang

et al. 2021

Front. Cell Dev. Biol.

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Accumulating evidence has supported that osteosarcoma is heterogeneous, and several subtypes have been identified based on genomic profiling. Immunotherapy is revolutionizing cancer treatment and is a promising therapeutic strategy. In contrast, few studies have identified osteosarcoma classification based on immune biosignatures, which offer the optimal stratification of individuals befitting immunotherapy. Here, we classified osteosarcoma into two clusters: immunity high and immunity low using the single-sample gene-set enrichment analysis and unsupervised hierarchical clustering. Immunity_H subtype was associated with high immune cells infiltration, a favorable prognosis, benefit to immunotherapy, high human leukocyte antigen gene expression, and activated immune signal pathway indicating an immune-hot phenotype. On the contrary, the Immunity_L subtype was correlated with low immune cell infiltration, poor prognosis, and cancer-related pathway, indicating an immune-cold phenotype. We also identified TYROBP as a key immunoregulatory gene associated with CD8+ T cell infiltration by multiplex immunohistochemistry. Finally, we established an immune-related prognostic model that predicted the survival time of osteosarcoma. In conclusion, we established a new classification system of osteosarcoma based on immune signatures and identified TYROBP as a key immunoregulatory gene. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of osteosarcoma patients.

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Section: Discussionsupporting

confidence: 83%

Classification of Osteosarcoma Based on Immunogenomic Profiling

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…Studies show that high TYROBP expression in breast cancer cells is correlated with bone metastasis and poor prognosis [ 45 ]. Besides, Ping Wu et al and Junjie Jiang et al reveal that TYROBP is a potential prognostic biomarker for clear cell renal cell carcinoma and gastric cancer [ 14 , 15 ]. Although the correlation between TYROBP expression and LGG has not been elucidated so far, our results indicate that TYROBP is a prognostic biomarker of LGG plays an essential role in its progression.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, Qisheng Peng et al showed that DAP12 inhibit LPS signaling in macrophages to prevent inflammation through physically combined with DOK3 [ 13 ]. TYROBP is an established oncogene for clear cell renal cell carcinoma and gastric cancer [ 14 , 15 ]. Kopatz et al showed that microglia can phagocytose glioma cells via the Siglec-h receptor for apoptosis induction, which indicates an important role of immune cell infiltration in glioma progression [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Elevated TYROBP expression predicts poor prognosis and high tumor immune infiltration in patients with low-grade glioma

Peng

Huang

et al. 2021

BMC Cancer

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Background Tyrosine protein tyrosine kinase binding protein (TYROBP) binds non-covalently to activated receptors on the surface of various immune cells, and mediates signal transduction and cellular activation. It is dysregulated in various malignancies, although little is known regarding its role in low-grade glioma. The aim of this study is to explore the clinicopathological significance, prognostic value and immune signature of TYROBP expression in low-grade glioma (LGG). Methods The differentially expressed genes (DEGs) between glioma samples and normal tissues were identified from two GEO microarray datasets using the limma package. The DEGs overlapping across both datasets were functionally annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. STRING database was used to establish the protein-protein interaction (PPI) of the DEGs. The PPI network was visualized by Cytoscape and cytoHubba, and the core module and hub genes were identified. The expression profile of TYROBP and patient survival were validated in the Oncomine, GEPIA2 and CGGA databases. The correlation between TYROBP expression and the clinicopathologic characteristics were evaluated. Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed by R based on the LGG data from TCGA. The TIMER2.0 database was used to determine the correlation between TYROBP expression and tumor immune infiltrating cells in the LGG patients. Univariate and multivariate Cox regression analyses were performed to determine the prognostic impact of clinicopathological factors via TCGA database. Results Sixty-two overlapping DEGs were identified in the 2 datasets, and were mainly enriched in the response to wounding, focal adhesion, GTPase activity and Parkinson disease pathways. TYROBP was identified through the PPI network and cytoHubba. TYROBP expression levels were significantly higher in the LGG tissues compared to the normal tissues, and was associated with worse prognosis and poor clinicopathological parameters. In addition, GSEA showed that TYROBP was positively correlated to neutrophil chemotaxis, macrophage activation, chemokine signaling pathway, JAK-STAT signaling pathway, and negatively associated with gamma aminobutyric acid signaling pathway, neurotransmitter transport, neuroactive ligand receptor intersection etc. TIMER2.0 and ssGSEA showed that TYROBP expression was significantly associated with the infiltration of neutrophils, macrophages, myeloid dendritic cells and monocytes. The infiltration of the M2 phenotype macrophages, cancer-associated fibroblasts and myeloid dendritic cells correlated to worse prognosis in LGG patients. Finally, multivariate analysis showed that elevated TYROBP expression is an independent risk factor for LGG. Conclusion TYROBP is dysregulated in LGG and correlates with immune infiltration. It is a potential therapeutic target and prognostic marker for LGG.

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“…Recent studies have shown that high expression of CD163 is related to a poor prognosis in breast cancer ( 53 ) and glioma ( 54 ) patients. TYROBP is mainly involved in immune signaling pathways, but an increasing number of studies have shown that TYROBP can be used as a prognostic marker for cancer ( 55 , 56 ). We found that the hub nine genes were mainly located in the extracellular matrix and cell membrane, which may indicate that they promote tumor progression by regulating the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

et al. 2021

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BackgroundGastric cancer is a common gastrointestinal malignancy. Since it is often diagnosed in the advanced stage, its mortality rate is high. Traditional therapies (such as continuous chemotherapy) are not satisfactory for advanced gastric cancer, but immunotherapy has shown great therapeutic potential. Gastric cancer has high molecular and phenotypic heterogeneity. New strategies for accurate prognostic evaluation and patient selection for immunotherapy are urgently needed.MethodsWeighted gene coexpression network analysis (WGCNA) was used to identify hub genes related to gastric cancer progression. Based on the hub genes, the samples were divided into two subtypes by consensus clustering analysis. After obtaining the differentially expressed genes between the subtypes, a gastric cancer risk model was constructed through univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis. The differences in prognosis, clinical features, tumor microenvironment (TME) components and immune characteristics were compared between subtypes and risk groups, and the connectivity map (CMap) database was applied to identify potential treatments for high-risk patients.ResultsWGCNA and screening revealed nine hub genes closely related to gastric cancer progression. Unsupervised clustering according to hub gene expression grouped gastric cancer patients into two subtypes related to disease progression, and these patients showed significant differences in prognoses, TME immune and stromal scores, and suppressive immune checkpoint expression. Based on the different expression patterns between the subtypes, we constructed a gastric cancer risk model and divided patients into a high-risk group and a low-risk group based on the risk score. High-risk patients had a poorer prognosis, higher TME immune/stromal scores, higher inhibitory immune checkpoint expression, and more immune characteristics suitable for immunotherapy. Multivariate Cox regression analysis including the age, stage and risk score indicated that the risk score can be used as an independent prognostic factor for gastric cancer. On the basis of the risk score, we constructed a nomogram that relatively accurately predicts gastric cancer patient prognoses and screened potential drugs for high-risk patients.ConclusionsOur results suggest that the 7-gene signature related to tumor progression could predict the clinical prognosis and tumor immune characteristics of gastric cancer.

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Identification of TYROBP and C1QB as Two Novel Key Genes With Prognostic Value in Gastric Cancer by Network Analysis

Cited by 32 publications

References 63 publications

Classification of Osteosarcoma Based on Immunogenomic Profiling

Classification of Osteosarcoma Based on Immunogenomic Profiling

Elevated TYROBP expression predicts poor prognosis and high tumor immune infiltration in patients with low-grade glioma

A Tumor Progression Related 7-Gene Signature Indicates Prognosis and Tumor Immune Characteristics of Gastric Cancer

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