Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients

Cai, Hai; Chen, Hang; Huang, Qi; Zhu, Jiang; Ke, Zhi‐Bin; Lin, Yunzhi; Zheng, Qing‐Shui; Wei, Yong; Xu, Ning; Xue, Xue-Yi

doi:10.3389/pore.2021.1609941

Cited by 8 publications

(7 citation statements)

References 42 publications

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“…Several cancers, including bladder cancer and glioma, exhibited immune cell infiltration associated with URGs, which can provide novel therapeutic targets. The common ubiquitination-related subtypes showed significant differences in immune cell infiltration, stromal scores, ESTIMATE scores, and immune scores ( Cai et al, 2021 ). According to the investigation of the immune microenvironment in gliomas, this risk grouping could be used as a guide for common glioma immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

et al. 2023

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Breast cancer (BC) is one of the most common tumor types and has poor outcomes. In this study, a ubiquitination-related prognostic signature was constructed, and its association with immunotherapy response in BC was explored. A list of ubiquitination-related genes was obtained from the molecular signatures database, and a ubiquitination-related gene signature was obtained by least absolute shrinkage and selection operator Cox regression. The genes, TCN1, DIRAS3, and IZUMO4, had significant influence on BC outcomes. Patients were categorized into two clusters—a high-risk group with poor survival and a low-risk group with greater chances of controlling BC progression. Univariate and multivariate Cox regression analyses revealed that the risk signature was an independent prognostic factor for BC. Gene set enrichment analysis suggested that the high-risk group was enriched in cell cycle and DNA replication pathways. The risk score was positively linked to the tumor microenvironment and negatively correlated with the immunotherapy response. The IC50 values for rapamycin were higher in the low-risk group, whereas those for axitinib, AZD6244, erlotinib, GDC0941, GSK650394, GSK269962A, lapatinib, and PD0325901 were higher in the high-risk group. Therefore, the ubiquitination-related signature is considered a promising tool for predicting a BC patient’s immunotherapy response.

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Section: Discussionmentioning

confidence: 99%

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

et al. 2023

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“…Recently, the role of ubiquitination-related regulators in the occurrence and outcome of pancreatic cancer has been deeply researched, which can influence the occurrence, progression, metastasis, and treatment response of various cancers (Ma et al 2020 ; Sun et al 2020 ; Chen et al 2021 ). Ubiquitination-related prognostic signatures have been developed for estimating the prognosis of several types of cancers (Cai et al 2021 ; Wu et al 2021 ; Zhou et al 2021 ). In our research, the expression characteristics and prognostic performances of URGs in PAAD were systematically explored to classify different ubiquitination-related clusters and a novel prognostic signature was precisely established for disease stratification.…”

Section: Discussionmentioning

confidence: 99%

“…The significant role of ubiquitination in cancer development and progression has been demonstrated in multiple reviews, which detailly comments the regulating mechanism of ubiquitination-related biomolecules on neoplastic diseases (Hoeller and Dikic 2009 ; Kirkin and Dikic 2011 ; Lipkowitz and Weissman 2011 ; Deng et al 2020 ). There have been reports that ubiquitination-related regulators are discovered to evaluate the prognostic prediction in renal cell carcinoma and bladder cancers (Cai et al 2021 ; Wu et al 2021 ; Zhou et al 2021 ). Additionally, studies in vivo and vitro display that ubiquitination-related regulators, such as COP9 signalosome complex subunit 6 (CSN6) and F-box protein 22 (FBXO22), participate in the progression of PAAD (Ma et al 2020 ; Chen et al 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A prospective prognostic signature for pancreatic adenocarcinoma based on ubiquitination-related mRNA-lncRNA with experimental validation in vitro and vivo

Wang

Yuan

et al. 2023

Funct Integr Genomics

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Ubiquitination-related genes (URGs) exerted a crucial part in a variety of human disease disorders; however, their association with pancreatic adenocarcinoma (PAAD) had yet to be clearly described. We aimed to comprehensively characterize the contributions of URGs in PAAD through in silico analysis and experimental validation, and then identified a robust mRNA-lncRNA-based molecular prognostic panel for patients with PAAD using bulk RNA-sequencing and single-cell RNA-sequencing data. Initially, we collected the multi-omics data from TCGA platform to depict a comprehensive landscape of URGs in pan-cancer. Furthermore, we were accurate to PAAD for in-depth analysis. Significant differences of the activation of ubiquitination pathways and the expression of URGs were detected between normal and malignant cells. Unsupervised hierarchical clustering determined two PAAD subtypes with distinct clinical outcomes, ubiquitination pathway activities, immune microenvironment, and functional annotation characteristics. The expression profiles of ubiquitination-associated mRNAs and lncRNAs in the training and validation datasets were utilized to develop and verify a novel ubiquitination-related mRNA-lncRNA prognostic panel, which had a satisfied prediction efficiency. Our ubiquitination-associated model could function as an effective prognostic index and outperformed four other recognized panels in evaluating PAAD patients’ survival status. Tumor immune microenvironment, mutation burden, and chemotherapy response were intensively explored to demonstrate the underlying mechanism of prognostic difference according to our panel. Our findings also revealed that FTI-277, a farnesyltransferase inhibitor, had a better curative effect in high-risk patients, while MK-2206, an Akt allosteric inhibitor, had a superior therapeutic effect in low-risk patients. The real-time PCR results uncovered the RNA expression of AC005062.1 in all the three PAAD cell lines was elevated several thousandfold. In conclusion, our URGs-based classification panel could be triumphantly served as a prediction tool for survival evaluation in patients with PAAD, and the genes in this panel could be developed as a potential target in PAAD therapy.

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“…Moreover, silencing UBE2T induced cell cycle arrest at the G 2 /M phase and increased apoptosis; thus, it may be considered a potential biomarker and therapeutic target for BC (101). Univariate Cox regression results showed that it was potential ubiquitination-related prognostic molecule, and it was verified to be associated with OS (102). High expression of UBE2T was positively correlated with advanced pathological stage, distant metastasis, histological grade and maximum tumor diameter.…”

Section: Expression Of Ube2t In Cancermentioning

confidence: 91%

Diverse roles of UBE2T in cancer (Review)

Yan

et al. 2023

Oncol Rep

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As a leading cause of mortalities worldwide, cancer results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in cancer, particularly aberrant ubiquitination, has drawn increasing interest in recent years. The present study aimed to review the roles of ubiquitin-conjugating enzyme E2 T (UBE2T) and its associated pathways in the pathogenesis of pan-cancer, and the development of small-molecule modulators to regulate ubiquitination for treatment strategies. The current study comprehensively investigated the expression landscape and functional significance of UBE2T, as well as its correlation with cancer cell sensitivity to chemotherapy/radiotherapy. Multiple levels of evidence suggested that aberrant UBE2T played important roles in pan-cancer. Information was collected from 16 clinical trials on ubiquitin enzymes, and it was found that these molecules had an important role in the ubiquitin-proteasome system. Further studies are necessary to explore their feasibility and effectiveness as diagnostic and prognostic biomarkers, or as up/down-stream and therapeutic targets for cancer treatment.

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Ubiquitination-Related Molecular Subtypes and a Novel Prognostic Index for Bladder Cancer Patients

Cited by 8 publications

References 42 publications

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

Prognostic implication and immunotherapy response prediction of a ubiquitination-related gene signature in breast cancer

A prospective prognostic signature for pancreatic adenocarcinoma based on ubiquitination-related mRNA-lncRNA with experimental validation in vitro and vivo

Diverse roles of UBE2T in cancer (Review)

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