Identification of TYROBP and FCER1G as Key Genes with Prognostic Value in Clear Cell Renal Cell Carcinoma by Bioinformatics Analysis

Wang, Licheng; Lin, Yun; Yuan, Yi; Liu, Fei; Sun, Kai

doi:10.1007/s10528-021-10061-y

Cited by 11 publications

(16 citation statements)

References 46 publications

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“…The prognostic role of FCER1G expression in ccRCC has been previously discovered through proteinprotein interaction networks (25) or weighted gene co-expression network (26) analysis of DEGs using open-source bulk RNA-sequencing data of ccRCC. Another study used the pre-established ESTMATE algorithm (41) to assess the genes with prognostic value in the immune microenvironment of ccRCC, identifying FCER1G as a candidate gene (28).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, there are no studies conducted thus far that investigated the correlation of FECER1G expression with macrophages or validated their ndings in a large clinical cohort. Although the GSEA analysis of high FCER1G expression was performed using TCGA-KIRC (25), the investigator failed to fully interpret the function of FCER1G in suppressing T cells in ccRCC.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we selected FCER1G as the most pronounced macrophage-related DEG with prognostic value for further exploration of its function in ccRCC. The literature review revealed that the differentially expression of FCER1G has been previously reported and has prognostic importance in TCGA-KIRC database (25,26). Concerning the close relationship of FCER1G with tumor immunity, we downloaded the bulk RNA-seq and clinical data of the CheckMate 025 clinical trial, based on which Nivolumab (anti-PD1) was approved by the Food and Drug Administration for the treatment of ccRCC, to further investigate the prognostic value of FCER1G (20).…”

Section: Fcer1g Was Abundantly Expressed In Ccrcc and Contributed To Poor Prognosis In Patients Receiving Anti-pd1 Treatmentmentioning

confidence: 93%

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FCER1G Positively Relates To Macrophage Infiltration In Clear Cell Renal Cell Carcinoma And Contributes To Unfavorable Prognosis By Regulating Tumor Immunity

Dong

Chen

Pan

et al. 2021

Preprint

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Background: Tumor-associated macrophages (TAMs) are closely related to unfavorable prognosis of patients with clear cell renal cell carcinoma (ccRCC). However, the important molecules in the interaction between ccRCC and TAMs are unclear.Methods: TCGA-KIRC gene expression data of tumor tissues and normal tissues adjacent to tumor were compared to identify differentially expressed genes in ccRCC. TAMs related genes were discovered by analyzing the correlation between these differentially expressed genes and common macrophage biomarkers. Gene set enrichment analysis was performed to predict functions of TAMs related gene. The findings were further validated using RNA sequencing data obtained from the CheckMate 025 study and immunohistochemical analysis of samples from 350 patients with ccRCC. Kaplan–Meier survival curve, Cox regression analysis and Harrell’s concordance index analysis were used to determine the prognostic significance.Results: In this study, we applied bioinformatic analysis to explore TAMs related differentially expressed genes in ccRCC and identified 5 genes strongly correlated with all selected macrophage biomarkers: STAC3, LGALS9, TREM2, FCER1G, and PILRA. Among them, FCER1G was abundantly expressed in tumor tissues and showed prognostic importance in patients with ccRCC who received treatment with Nivolumab; however, it did not exhibit prognostic value in those treated with Everolimus. We also discovered that high expression levels of FCER1G are related to T cell suppression. Moreover, combination of FCER1G and macrophage biomarker CD68 can improve the prognostic stratification of patients with ccRCC from TCGA-KIRC. Based on the immunohistochemical analysis of samples from patients with ccRCC, we further validated that FCER1G and CD68 are both highly expressed in tumor tissue and correlate with each other. Higher expression of CD68 or FCER1G in ccRCC tissue indicates shorter overall survival and progression-free survival; patients with high expression of both CD68 and FCER1G have the worst outcome. Combining CD68 and FCER1G facilitates the screening of patients with a worse prognosis from the same TNM stage group.Conclusions: High expression of FCER1G in ccRCC is closely related to TAMs infiltration and suppression of T cell function. Combining the expression levels of FCER1G and macrophage biomarker CD68 may be a promising postoperative prognostic index for patients with ccRCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Fcer1g Was Abundantly Expressed In Ccrcc and Contributed To Poor Prognosis In Patients Receiving Anti-pd1 Treatmentmentioning

confidence: 93%

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FCER1G Positively Relates To Macrophage Infiltration In Clear Cell Renal Cell Carcinoma And Contributes To Unfavorable Prognosis By Regulating Tumor Immunity

Dong

Chen

Pan

et al. 2021

Preprint

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“…As transmembrane immune signaling adaptor proteins, TYROBP and FCER1G may mediate an intracellular signal via immunoreceptor tyrosine-based activation motif (ITAM) to up-regulate the expression of SPI1 and then initiate the whole SPI1-TYROBP-FCER1G network for a competent immunological surveillance function with upregulated immune infiltrations in tumor microenvironment [ 60 – 63 ]. SPI1, as an oncogene, is also an important transcription factor for monocyte and macrophage identity.…”

Section: Discussionmentioning

confidence: 99%

The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration

Shi

Yuan

et al. 2022

BMC Cancer

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Osteosarcoma is an aggressive malignant bone sarcoma worldwide. A causal gene network with specific functions underlying both the development and progression of OS was still unclear. Here we firstly identified the differentially expressed genes (DEGs) between control and OS samples, and then defined the hub genes and top clusters in the protein–protein interaction (PPI) network of these DEGs. By focusing on the hub gene TYROBP in the top 1 cluster, a conserved TYROBP co-expression network was identified. Then the effect of the network on OS overall survival was analyzed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and Gene Set Enrichment Analysis (GSEA) were used to explore the functions of the network. XCell platform and ssGSEA algorithm were conducted to estimate the status of immune infiltration. ChEA3 platform, GSEA enrichment analysis, and Drug Pair Seeker (DPS) were used to predict the key transcription factor and its upstream signal. We identified the downregulated SPI1-TYROBP-FCER1G network in OS, which were significantly enriched in immune-related functions. We also defined a two-gene signature (SPI1/FCER1G) that can predict poorer OS overall survival and the attenuated immune infiltration when downregulated. The SPI1-TYROBP-FCER1G network were potentially initiated by transcription factor SPI1 and would lead to the upregulated CD86, MHC-II, CCL4/CXCL10/CX3CL1 and hence increased immune infiltrations. With this study, we could better explore the mechanism of OS oncogenesis and metastasis for developing new therapies.

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“…The missense mutations in the coding region of the TYROBP were closely related to the AD risk [24]. Besides, the ccRCC tissues had a signi cantly higher TYROBP expression than the normal tissues, and its overexpression led to a lower survival probability in ccRCC patients [25]. The elevated level of TYROBP was observed in nearly 66% of the breast cancers, which was related to the worse prognosis of breast cancer patients [26].…”

Section: Discussionmentioning

confidence: 99%

TYRO Protein Tyrosine Kinase-binding Protein Predicts Favorable Overall Survival in Osteosarcoma and Correlates With Antitumor Immunity

Chen

Shen

et al. 2022

Preprint

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Objective: To explore the prognostic significance and underlying mechanism of TYRO protein tyrosine kinase-binding protein (TYROBP) in osteosarcoma. Methods: Firstly, the expression of TYROBP was analyzed using the t-test. The Kaplan-Meier plotter analysis and a receiver operating characteristic (ROC) curve were performed to evaluate the influence of TYROBP on overall survival (OS). Further, Cox regression analysis was conducted to predict the independent prognostic factors for OS of osteosarcoma patients, and a nomogram was constructed. Then, the relationship between TYROBP and clinicopathological characteristics was determined using statistical methods. Enrichment analyses were conducted to evaluate the biological functions of TYROBP. Finally, ESTIMATE algorithm was used to assess the association of TYROBP with immune cell infiltration. Results: TYROBP was significantly increased in osteosarcoma (all P <0.001). However, the high expression of TYROBP was related to better OS of osteosarcoma patients. Cox regression analysis showed that TYROBP was an independent prognostic factor for predicting OS (P =0.005), especially in patients with male sex, age <18 years, metastasis, and tumor site leg/foot (all P <0.05). Besides, TYROBP mRNA expression was significantly associated with tumor site (P <0.01) but had no remarkable relationship with age, gender, and metastasis status (all P>0.05). Functional annotation and GSEA revealed that TYROBP was mainly involved in immune-related pathways. Importantly, TYROBP positively correlated with immune scores (P <0.001, r=0.87). Conclusions: TYROBP served as an independent prognostic biomarker for OS in osteosarcoma. High TYROBP expression might prolong the survival of osteosarcoma patients mainly through promoting antitumor immunity.

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Identification of TYROBP and FCER1G as Key Genes with Prognostic Value in Clear Cell Renal Cell Carcinoma by Bioinformatics Analysis

Cited by 11 publications

References 46 publications

FCER1G Positively Relates To Macrophage Infiltration In Clear Cell Renal Cell Carcinoma And Contributes To Unfavorable Prognosis By Regulating Tumor Immunity

FCER1G Positively Relates To Macrophage Infiltration In Clear Cell Renal Cell Carcinoma And Contributes To Unfavorable Prognosis By Regulating Tumor Immunity

The role of SPI1-TYROBP-FCER1G network in oncogenesis and prognosis of osteosarcoma, and its association with immune infiltration

TYRO Protein Tyrosine Kinase-binding Protein Predicts Favorable Overall Survival in Osteosarcoma and Correlates With Antitumor Immunity

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