The Prognostic Value and Immune Infiltration of USP10 in Pan-Cancer: A Potential Therapeutic Target

Gao, Dedong; Zhang, Zhiwen; Rui, Xu; He, Zuming; Li, Fangyi; Hu, Yan; Chen, Hui; Lü, Jining; Cao, Xingguo; Liu, Yali; Xu, Zeng‐Guang

doi:10.3389/fonc.2022.829705

Cited by 7 publications

(4 citation statements)

References 48 publications

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“…Innate immune response has been proven to be activated in murine CML and further enhanced by TKI or alpha-interferon treatment [33,34]. Bioinformatic studies in several cancers have shown that ubiquitination is implicated in immune infiltrates and pathways [35][36][37]. In our study, CML is correlated with an impaired immune response, indicated by the low scores of T cells regulatory, Macrophages M2, activated dendritic cells, neutrophils, plasma cells and resting mast cells and the high scores of monocytes, activated CD4 + memory T cells and activated NK cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of ubiquitination-related hub genes in chronic myeloid leukemia cell by bioinformatics analysis

Zhou,

Li,

Meng

et al. 2024

J. Cancer

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Purpose: Chronic myeloid leukemia stem cells (CML-LSCs) are posited as the primary instigators of resistance to tyrosine kinase inhibitors (TKIs) and recurrence of CML. Ubiquitination, a post-translational modification, has been implicated in the worsening process of CML. A more detailed understanding of their crosstalk needs further investigation. Our research aims to explore the potential ubiquitination-related genes in CML-LSC using bioinformatics analysis that might be the target for the eradication of LSCs. Methods: The ubiquitination modification-related differentially expressed genes (UUC-DEGs) between normal hematopoietic stem cells (HSCs) and LSCs were obtained from GSE47927 and iUUCD database. Subsequently, the hub UUC-DEGs were identified through protein-protein interaction (PPI) network analysis utilizing the STRING database and the MCODE plug-in within the Cytoscape platform. The upstream regulation network of the hub UUC-DEGs was studied by hTFtarget, PROMO, miRDB and miRWalk databases respectively. Then the correlation between the hub UUC-DEGs and the immune cells was analyzed by the CIBERSORT algorithm and "ggcorrplot" package. Finally, we validated the function of hub UUC-DEGs in CML animal models, CML cell lines and CD34 + cells of the GSE24739 dataset. Results: There is a strong association between the 4 hub UUC genes (AURKA, Fancd2, Cdc20 and Uhrf1) of LSCs and the infiltration of CD4 + /CD8 + T cells, NK cells and monocytes. 8 TFs and 23 miRNAs potentially targeted these 4 hub genes were constructed. Among these hub genes, Fancd2, Cdc20 and Uhrf1 were found to be highly expressed in CML-LSC, which knocking down resulted in significant inhibition of CML cell proliferation. Conclusions: From the perspective of bioinformatics analysis, UHRF1 and CDC20 were identified as the novel key ubiquitination-related genes in CML-LSCs and the pathogenesis of CML.

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Section: Discussionmentioning

confidence: 99%

Identification of ubiquitination-related hub genes in chronic myeloid leukemia cell by bioinformatics analysis

Zhou,

Li,

Meng

et al. 2024

J. Cancer

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“…The study of Liu et al showed that USP10 could stabilize Yes1-associated transcriptional regulator expression which, whereafter enhanced cysteine rich angiogenic inducer 61 expression to promote immune escape and maintain cell proliferation and metastasis ability via the upregulation of PD-L1 and galectin-9 [ 24 ]. Recently, a bioinformatic study comprehensively analyzed the prognostic value and immune infiltration of USP10 in pan-cancer, especially in PDAC and hepatocellular carcinoma [ 32 ]. In this study, we found that USP10 was highly expressed in PDAC tissues, and high USP10 expression also indicated a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

USPs in Pancreatic Ductal Adenocarcinoma: A Comprehensive Bioinformatic Analysis of Expression, Prognostic Significance, and Immune Infiltration

Wang

Zhou

Kong

et al. 2022

BioMed Research International

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Pancreatic ductal adenocarcinoma (PDAC), as an intractable malignancy, still causes an extremely high mortality worldwide. The ubiquitin-specific protease (USP) family constitutes the major part of deubiquitinating enzymes (DUBs) which has been reported to be involved in initiation and progression of various malignancies via the function of deubiquitination. However, the biological function and clinical values of USPs in PDAC have not been comprehensively elucidated. In this study, Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) datasets, UALCAN database, and the Human Protein Atlas (HPA) online tool were used to analyze the expression level and the relationship between USP expression and clinicopathological features in PDAC. Survival module of HPA and Kaplan-Meier plotter (KMP) databases was recruited to explore the prognostic value of USPs. Tumor Immune Estimation Resource (TIMER) online tool and KMP databases were utilized to elucidate tumor immune infiltration and immune-related survival of USPs. CBioPortal online tool was used to identify the gene mutation level of USPs in PDAC. Both cBioPortal and LinkedOmics were used to confirm the potential biological functions of USPs in PDAC. Our study showed that USP10, USP14, USP18, USP32, USP33, and USP39 (termed as six-USPs) expressions were significantly elevated in tumor tissues. The high expression of the four USPs (USP10, USP14, USP18, and USP39) indicated a poor prognosis. A significant relationship was indicated between the expression of six-USPs and clinicopathological features. Also, the expression of six-USPs was related to promoter methylation level. Moreover, more than 40% genetic alterations and mutations were discovered in six-USPs. Furthermore, the six-USP expression was correlated with immune infiltration and immune-related prognosis. The functional analysis found that the six-USPs were involved in various biological processes and signaling pathways, such as nucleocytoplasmic transport, choline metabolism in cancer, cell cycle, ErbB signaling pathway, RIG-I-like receptor signaling pathway, TGF-β signaling pathway, and TNF signaling pathway. In conclusion, the results showed that six-USPs are potential prognostic biomarkers and can be recruited as possible therapeutic targets of PDAC.

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“…TLRs can promote inflammation and immune response in tumors, suggesting a potential role for USP10 in the regulation of immune pathways. Growing evidence suggests that USP10 may be involved in the infiltration of various immune cells in tumors, potentially regulating the infiltration levels of specific immune cells (98); however, its precise role in tumor immune response remains unclear. We further analyzed data from the TISIDB (http://cis.hku.hk/TISIDB/index.php) to evaluate the correlation between USP10 and immunostimulatory molecules, immunosuppressive molecules, major histocompatibility complex (MHC) molecules, chemokines, and MHC receptors, to better understand the immune function of USP10 in cancer regulation.…”

Section: Usp10 Regulates the Immune Response In Tumorsmentioning

confidence: 99%

Ubiquitin-specific peptidase 10, a deubiquitinating enzyme: Assessing its role in tumor prognosis and immune response

Chen²,

Huang³

et al. 2022

Front. Oncol.

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Ubiquitin-specific peptidase 10 (USP10) is a member of the ubiquitin-specific protease family that removes the ubiquitin chain from ubiquitin-conjugated protein substrates. We performed a literature search to evaluate the structure and biological activity of USP10, summarize its role in tumorigenesis and tumor progression, and discuss how USP10 may act as a tumor suppressor or a tumor-promoting gene depending on its mechanism of action. Subsequently, we elaborated further on these results through bioinformatics analysis. We demonstrated that abnormal expression of USP10 is related to tumorigenesis in various types of cancer, including liver, lung, ovarian, breast, prostate, and gastric cancers and acute myeloid leukemia. Meanwhile, in certain cancers, increased USP10 expression is associated with tumor suppression. USP10 was downregulated in kidney renal clear cell carcinoma (KIRC) and associated with reduced overall survival in patients with KIRC. In contrast, USP10 upregulation was associated with poor prognosis in head and neck squamous cell carcinoma (HNSC). In addition, we elucidated the novel role of USP10 in the regulation of tumor immunity in KIRC and HNSC through bioinformatics analysis. We identified several signaling pathways to be significantly associated with USP10 expression, such as ferroptosis, PI3K/AKT/mTOR, TGF-β, and G2/M checkpoint. In summary, this review outlines the role of USP10 in various forms of cancer, discusses the relevance of USP10 inhibitors in anti-tumor therapies, and highlights the potential function of USP10 in regulating the immune responses of tumors.

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The Prognostic Value and Immune Infiltration of USP10 in Pan-Cancer: A Potential Therapeutic Target

Cited by 7 publications

References 48 publications

Identification of ubiquitination-related hub genes in chronic myeloid leukemia cell by bioinformatics analysis

Identification of ubiquitination-related hub genes in chronic myeloid leukemia cell by bioinformatics analysis

USPs in Pancreatic Ductal Adenocarcinoma: A Comprehensive Bioinformatic Analysis of Expression, Prognostic Significance, and Immune Infiltration

Ubiquitin-specific peptidase 10, a deubiquitinating enzyme: Assessing its role in tumor prognosis and immune response

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