Identification of a Necroptosis-Related Prognostic Index and Associated Regulatory Axis in Kidney Renal Clear Cell Carcinoma

Luo, Yunping; Zhang, Guian

doi:10.2147/ijgm.s367173

Cited by 15 publications

(7 citation statements)

References 36 publications

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“…Kidney renal clear cell carcinoma (KIRC) is the most common histological subtype of renal cell carcinoma, accounting for 80–90% of all cases, with a high degree of immune infiltration [ 1 , 2 , 3 ]. A better understanding of the immune system and a discovery that tumors can take advantage of immune checkpoints to promote their survival and growth have resulted in the creation of immune checkpoint inhibitors (ICIs) [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Wang

et al. 2022

Bioengineering

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Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent and deadly types of renal cancer in adults. Recent research has identified circadian genes as being involved in the development and progression of KIRC by altering their expression. This study aimed to identify circadian genes that are differentially expressed in KIRC and assess their role in KIRC progression. In KIRC, there were 553 differentially expressed rhythm genes (DERGs), with 300 up-regulated and 253 down-regulated DERGs. Functional enrichment analyses showed that DERGs were greatly enriched in the circadian rhythm and immune response pathways. Survival analyses indicated that higher expression levels of CSNK1E were related to shorter overall survival of KIRC patients, whereas lower expression levels of GNA11, KLF9, and THRAP3 were associated with shorter overall survival of KIRC patients. Through cell assay verification, the mRNA level of CSNK1E was significantly up-regulated, whereas the mRNA levels of GNA11, KLF9, and THRAP3 were dramatically down-regulated in KIRC cells, which were consistent with the bioinformatics analysis of KIRC patient samples. Age, grade, stage, TM classification, and CSNK1E expression were all shown to be high-risk variables, whereas GNA11, KLF9, and THRAP3 expression were found to be low-risk factors in univariate Cox analyses. Multivariate Cox analyses showed that CSNK1E and KLF9 were also independently related to overall survival. Immune infiltration analysis indicated that the proportion of immune cells varied greatly between KIRC tissues and normal tissue, whereas CSNK1E, GNA11, KLF9, and THRAP3 expression levels were substantially linked with the infiltration abundance of immune cells and immunological biomarkers. Moreover, interaction networks between CSNK1E/GNA11/KLF9/THRAP3 and immune genes were constructed to explore the stream connections. The findings could help us better understand the molecular mechanisms of KIRC progression, and CSNK1E/GNA11/KLF9/THRAP3 might be used as molecular targets for chronotherapy in KIRC patients in the near future.

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Section: Introductionmentioning

confidence: 99%

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Wang

et al. 2022

Bioengineering

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“…There are three studies reporting necroptosis-related genes in KIRC [ 49 – 51 ], however, these three articles only roughly described the necroptosis-related genes level in RCC. We enriched these necroptosis-related genes and found that these necroptosis-related genes may be related to immunity in renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Necroptosis-related genes are associated with prognostic features of kidney renal clear cell carcinoma

Wang,

Pan,

Chen

2023

Discov Onc

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Introduction Renal clear cell carcinoma is a common type of cancer in the adult urological system. It has a high mortality rate, with 30% of patients developing metastasis and 60% dying within 1–2 years of diagnosis. Recent advancements in tumor immunology and necroptosis have provided new insights into kidney cancer therapy. Therefore, it is crucial to identify potential targets for combining immunotherapy with necroptosis. Materials and methods Using the GSE168845 dataset and necroptosis-related genes, we identified genes that are differentially expressed in relation to necroptosis. We analyzed the prognostic value of these genes through differential expression analysis, prognostic analysis, and Cox regression analysis. The expression levels of the MYCN and CDKN2A genes were verified using the GSE53757 dataset. We also examined the association between the differentially expressed genes and clinicopathological features, as well as overall survival in our cohorts. In addition, we constructed a lasso Cox regression model to assess the correlation between these genes and immune score, ICP, and OCLR score. We conducted qRT-PCR to detect the expression of MYCN, CDKN2A, and ZBP1 in different samples of kidney renal clear cell carcinoma (KIRC). The expression levels of these genes were verified in a normal kidney cell line (HK-2 cells) and two KIRC cell lines (786-O, ACHN). The protein levels of MYCN and CDKN2A were detected using immunohistochemistry (IHC). SiRNA was used to silence the expression of MYCN and CDKN2A in the ACHN cell line, and wound healing assays were performed to measure cell migration. Results MYCN, CDKN2A, and ZBP1 were identified as necroptosis-related genes with independent prognostic value, leading to the development of a risk prognostic model. The expression of the CDKN2A gene was significantly higher in KIRC tissues compared to normal tissues, while the expression of the MYCN gene was significantly lower in KIRC tissues. The expression of MYCN and CDKN2A was associated with tumor stage, metastasis, and overall survival in our cohort. Furthermore, MYCN, CDKN2A, and ZBP1 were significantly correlated with immune score, ICP, and OCLR score. The expression levels of CDKN2A and ZBP1 were higher in KIRC cells compared to normal kidney cells, while the expression of MYCN was lower in KIRC cells. The protein expression of MYCN and CDKN2A was also higher in KIRC tissues, as confirmed by IHC. The results of the wound healing assay indicated that silencing CDKN2A inhibited cell migration, while silencing MYCN enhanced cell migration. Conclusions MYCN and CDKN2A are potential targets and valuable prognostic biomarkers for combining immunotherapy with necroptosis in kidney renal clear cell carcinoma. CDKN2A promotes the migration of renal cancer cells, while MYCN inhibits their migration.

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“…Studies have also shown that necroptosis-related genes are promising biomarkers for predicting prognosis and treatment response in ccRCC ( Luo and Zhang, 2022 ). Necroptosis-related signatures have also been demonstrated as novel prognostic predictors of immune microenvironment and treatment response in ccRCC ( Chen et al, 2022b ).…”

Section: Discussionmentioning

confidence: 99%

A novel marker based on necroptosis-related long non-coding RNA for forecasting prognostic in patients with clear cell renal cell carcinoma

et al. 2022

Front. Genet.

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Background: The incidence of clear cell renal cell carcinoma (ccRCC) is high and has increased gradually in recent years. At present, due to the lack of effective prognostic indicators, the prognosis of ccRCC patients is greatly affected.Necroptosis is a type of cell death, and along with cell necrosis is considered a new cancer treatment strategy. The aim of this study was to construct a new marker for predicting the prognosis of ccRCC patients based on long non-coding RNA (nrlncRNAs) associated with necroptosis.Methods: RNA sequence data and clinical information of ccRCC patients from the Cancer Genome Atlas database (TCGA) were downloaded. NrlncRNA was identified by Pearson correlation study. The differentially expressed nrlncRNA and nrlncRNA pairs were identified by univariate Cox regression and Lasso-Cox regression. Finally, a Kaplan-Meier survival study, Cox regression, clinicopathological features correlation study, and receiver operating characteristic (ROC) spectrum were used to evaluate the prediction ability of 25-nrlncrnas for markers. In addition, correlations between the risk values and sensitivity to tumor-infiltrating immune cells, immune checkpoint inhibitors, and targeted drugs were also investigated.Results: In the current research, a novel marker of 25-nrlncRNAs pairs was developed to improve prognostic prediction in patients with ccRCC. Compared with clinicopathological features, nrlncRNAs had a higher diagnostic validity for markers, with the 1-year, 3-years, and 5-years operating characteristic regions being 0.902, 0.835, and 0.856, respectively, and compared with the stage of 0.868, an increase of 0.034. Cox regression and stratified survival studies showed that this marker could be an independent predictor of ccRCC patients. In addition, patients with different risk scores had significant differences in tumor-infiltrating immune cells, immune checkpoint, and semi-inhibitory concentration of targeted drugs. The feature could be used to evaluate the clinical efficacy of immunotherapy and targeted drug therapy.Conclusion: 25-nrlncRNAs pair markers may help to evaluate the prognosis and molecular characteristics of ccRCC patients, which improve treatment methods and can be more used in clinical practice.

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Identification of a Necroptosis-Related Prognostic Index and Associated Regulatory Axis in Kidney Renal Clear Cell Carcinoma

Cited by 15 publications

References 36 publications

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Effects and Prognostic Values of Circadian Genes CSNK1E/GNA11/KLF9/THRAP3 in Kidney Renal Clear Cell Carcinoma via a Comprehensive Analysis

Necroptosis-related genes are associated with prognostic features of kidney renal clear cell carcinoma

A novel marker based on necroptosis-related long non-coding RNA for forecasting prognostic in patients with clear cell renal cell carcinoma

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