Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma

Wu, Yue; Zhang, Xi; Xian, Wa; Feng, Huan; Hu, Bintao; Deng, Zhiyao; Liu, Bo; Luan, Yang; Ruan, Yajun; Liu, Xiaohui; Liu, Zhuo; Liu, Jihong; Wang, Tao

doi:10.3389/fcell.2021.684643

Cited by 8 publications

(7 citation statements)

References 46 publications

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“…An integrated analysis of glycolysis-related genes in clear cell renal cell carcinoma (ccRCC) by Lv et al using TCGA and GEO datasets resulted in the construction of a seven-gene signature that predicted OS in ccRCC ( 17 ). The accuracy and generalizability of a prognostic signature for ccRCC created by Wu et al based on ubiquitin-related genes has been verified in an independent dataset derived from the ArrayExpress database ( 18 ). Verbiest et al found that the ccRCC molecular subtypes (ccrcc1 to 4), established based on unsupervised clustering of whole genome mRNA-expression data ( 19 ), could identify molecularly different patient populations and selected patients for systemic therapies, and they were predictive of sunitinib or pazopanib response in metastatic ccRCC ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 94%

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

et al. 2022

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Given the importance of tripartite motif (TRIM) proteins in diverse cellular biological processes and that their dysregulation contributes to cancer progression, we constructed a robust TRIM family signature to stratify patients with kidney renal clear cell carcinoma (KIRC). Transcriptomic profiles and corresponding clinical information of KIRC patients were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. Prognosis-related TRIM family genes were screened and used to construct a novel TRIM family-based signature for the training cohort. The accuracy and generalizability of the prognostic signature were assessed in testing, entire, and external ICGC cohorts. We analyzed correlations among prognostic signatures, tumor immune microenvironment, and immune cell infiltration. The results of univariate Cox regression and Kaplan-Meier survival analyses revealed 27 TRIMs that were robustly associated with the prognosis of patients with KIRC. We applied Lasso regression and multivariate Cox regression analyses to develop a prognostic signature containing the TRIM1, 13, 35, 26, 55, 2, 47, and 27 genes to predict the survival of patients with KIRC. The accuracy and generalizability of this signature were confirmed in internal and external validation cohorts. We also constructed a predictive nomogram based on the signature and the clinicopathological characteristics of sex, age, and T and M status to aid clinical decision-making. We analyzed immune cell infiltration analysis and found that CD8 T cells, memory resting CD4 T cells, and M2 macrophages were the most enriched components in the KIRC tumor immune microenvironment. A higher level of immune infiltration by plasma cells, follicular helper T cells, and activated NK cells, and a lower level of immune infiltration by memory resting CD4 T cells, M1 and M2 macrophages, and resting dendritic cells were associated with higher risk scores. Overall, our eight-gene TRIM family signature has sufficient accuracy and generalizability for predicting the overall survival of patients with KIRC. Furthermore, this prognostic signature is associated with tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 94%

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

et al. 2022

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“…A study demonstrated that the overexpression of MG53 in melanoma cells confers enhanced resistance to dacarbazine treatment, thereby highlighting its potential as a valuable strategy for improving chemical resistance ). An analysis of ubiquitinrelated genes in the cancer genome atlas queue revealed an association between MG53 and the prognosis of renal clear cell carcinoma (Wu et al, 2021). MG53 can also impede breast cancer progression by suppressing the activation of the PI3K/Akt/mTOR pathway (Wang et al, 2022).…”

Section: Mg53 and Other Cancersmentioning

confidence: 99%

MG53/TRIM72: multi-organ repair protein and beyond

Wang,

An,

et al. 2024

Front. Physiol.

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MG53, a member of the tripartite motif protein family, possesses multiple functionalities due to its classic membrane repair function, anti-inflammatory ability, and E3 ubiquitin ligase properties. Initially recognized for its crucial role in membrane repair, the therapeutic potential of MG53 has been extensively explored in various diseases including muscle injury, myocardial damage, acute lung injury, and acute kidney injury. However, further research has revealed that the E3 ubiquitin ligase characteristics of MG53 also contribute to the pathogenesis of certain conditions such as diabetic cardiomyopathy, insulin resistance, and metabolic syndrome. Moreover, recent studies have highlighted the anti-tumor effects of MG53 in different types of cancer, such as small cell lung cancer, liver cancer, and colorectal cancer; these effects are closely associated with their E3 ubiquitin ligase activities. In summary, MG53 is a multifunctional protein that participates in important physiological and pathological processes of multiple organs and is a promising therapeutic target for various human diseases. MG53 plays a multi-organ protective role due to its membrane repair function and its exertion of anti-tumor effects due to its E3 ubiquitin ligase properties. In addition, the controversial aspect of MG53’s E3 ubiquitin ligase properties potentially causing insulin resistance and metabolic syndrome necessitates further cross-validation for clarity.

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“…One study analyzed ubiquitin-related genes in The Cancer Genome Atlas cohort and found that MG53 was correlated strongly with the grade, stage, and T stage of clear cell renal cell carcinoma. However, the expression of MG53 in patients with clear cell renal cell carcinoma remains to be confirmed ( 54 ).…”

Section: Beneficial Effects Of Mg53 On Cancer Therapymentioning

confidence: 99%

Is MG53 a potential therapeutic target for cancer?

Du,

Li,

2023

Front. Endocrinol.

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Cancer treatment still encounters challenges, such as side effects and drug resistance. The tripartite-motif (TRIM) protein family is widely involved in regulation of the occurrence, development, and drug resistance of tumors. MG53, a member of the TRIM protein family, shows strong potential in cancer therapy, primarily due to its E3 ubiquitin ligase properties. The classic membrane repair function and anti-inflammatory capacity of MG53 may also be beneficial for cancer prevention and treatment. However, MG53 appears to be a key regulatory factor in impaired glucose metabolism and a negative regulatory mechanism in muscle regeneration that may have a negative effect on cancer treatment. Developing MG53 mutants that balance the pros and cons may be the key to solving the problem. This article aims to summarize the role and mechanism of MG53 in the occurrence, progression, and invasion of cancer, focusing on the potential impact of the biological function of MG53 on cancer therapy.

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Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma

Cited by 8 publications

References 46 publications

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

MG53/TRIM72: multi-organ repair protein and beyond

Is MG53 a potential therapeutic target for cancer?

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