Analyzing and validating the prognostic value and immune microenvironment of clear cell renal cell carcinoma

Ke, Jingwei; Chen, Jie; Liu, Xin

doi:10.1080/19768354.2022.2056635

Cited by 10 publications

(5 citation statements)

References 41 publications

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“…Immune cell infiltration plays an important role in tumorigenesis and development [ 44 , 45 ]. We investigated whether there were any differences in the genomes of patients in two risk cohorts.…”

Section: Resultsmentioning

confidence: 99%

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

Feng,

Li,

Meng

et al. 2024

Discov Onc

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Purpose This study aimed to construct an m6A and cuproptosis-related long non-coding RNAs (lncRNAs) signature to accurately predict the prognosis of kidney clear cell carcinoma (KIRC) patients using the information acquired from The Cancer Genome Atlas (TCGA) database. Methods First, the co-expression analysis was performed to identify lncRNAs linked with N6-methyladenosine (m6A) and cuproptosis in ccRCC. Then, a model encompassing four candidate lncRNAs was constructed via univariate, least absolute shrinkage together with selection operator (LASSO), and multivariate regression analyses. Furthermore, Kaplan–Meier, principal component, functional enrichment annotation, and nomogram analyses were performed to develop a risk model that could effectively assess medical outcomes for ccRCC cases. Moreover, the cellular function of NFE4 in Caki-1/OS-RC-2 cultures was elucidated through CCK-8/EdU assessments and Transwell experiments. Dataset outcomes indicated that NFE4 can have possible implications in m6A and cuproptosis, and may promote ccRCC progression. Results We constructed a panel of m6A and cuproptosis-related lncRNAs to construct a prognostic prediction model. The Kaplan–Meier and ROC curves showed that the feature had acceptable predictive validity in the TCGA training, test, and complete groups. Furthermore, the m6A and cuproptosis-related lncRNA model indicated higher diagnostic efficiency than other clinical features. Moreover, the NFE4 function analysis indicated a gene associated with m6A and cuproptosis-related lncRNAs in ccRCC. It was also revealed that the proliferation and migration of Caki-1 /OS-RC-2 cells were inhibited in the NFE4 knockdown group. Conclusion Overall, this study indicated that NFE4 and our constructed risk signature could predict outcomes and have potential clinical value.

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Section: Resultsmentioning

confidence: 99%

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

Feng,

Li,

Meng

et al. 2024

Discov Onc

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“…The tumor immune microenvironment plays an important role in tumor diagnosis, prevention, treatment, and prognosis [ 27 ]. Immune cells infiltrating tumors are an essential component of the tumor microenvironment, which is intimately linked to tumor cell proliferation, treatment response, and prognosis [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Elevated ADH5 expression suggested better prognosis in kidney renal clear cell carcinoma (KIRC) and related to immunity through single-cell and bulk RNA-sequencing

Sun,

Zhang,

et al. 2024

BMC Urol

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Background Despite the rapid advances in modern medical technology, kidney renal clear cell carcinoma (KIRC) remains a challenging clinical problem in urology. Researchers urgently search for useful markers to break through the therapeutic conundrum due to its high lethality. Therefore, the study explores the value of ADH5 on overall survival (OS) and the immunology of KIRC. Methods The gene expression matrix and clinical information on ADH5 in the TCGA database were validated using external databases and qRT-PCR. To confirm the correlation between ADH5 and KIRC prognosis, univariate/multivariate Cox regression analysis was used. We also explored the signaling pathways associated with ADH5 in KIRC and investigated its association with immunity. Results The mRNA and protein levels showed an apparent downregulation of ADH5 in KIRC. Correlation analysis revealed that ADH5 was directly related to histological grade, clinical stage, and TMN stage (p < 0.05). Univariate and multivariate Cox regression analysis identified ADH5 as an independent factor affecting the prognosis of KIRC. Enrichment analysis looked into five ADH5-related signaling pathways. The results showed no correlation between ADH5 and TMB, TNB, and MSI. From an immunological perspective, ADH5 was found to be associated with the tumor microenvironment, immune cell infiltration, and immune checkpoints. Lower ADH5 expression was associated with greater responsiveness to immunotherapy. Single-cell sequencing revealed that ADH5 is highly expressed in immune cells. Conclusion ADH5 could be a promising prognostic biomarker and a potential therapeutic target for KIRC. Besides, it was found that KIRC patients with low ADH5 expression were more sensitive to immunotherapy.

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“…The reason was that necrotic tumor cells could release IL-1α to activate dendritic cells (DCs) which could induce an anti-tumor immune response by producing cytotoxic IL-12 or activating CD8+ T cells ( Schmidt et al, 2015 ; Takemura et al, 2015 ). Meanwhile, the tumor immune microenvironment plays an important role in the diagnosis, prevention, treatment and prognosis of ccRCC ( Ke, Chen & Liu, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of prognostic and tumor microenvironment characteristics of necroptosis index and BIRC3 in clear cell renal cell carcinoma

Wei,

Zhang,

Yang

2023

PeerJ

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Background Necroptosis is a form of programmed cell death; it has an important role in tumorigenesis and metastasis. However, details of the regulation and function of necroptosis in clear cell renal cell carcinoma (ccRCC) remain unclear. It is necessary to explore the significance of necroptosis in ccRCC. Methods Necroptosis-related clusters were discerned through the application of Consensus Clustering. Based on the TCGA and GEO databases, we identified prognostic necroptosis-related genes (NRGs) with univariate COX regression analysis. The necroptosis-related model was constructed through the utilization of LASSO regression analysis, and the immune properties, tumor mutation burden, and immunotherapy characteristics of the model were assessed using multiple algorithms and datasets. Furthermore, we conducted comprehensive GO, KEGG, and GSVA analyses to probe into the functional aspects of biological pathways. To explore the expression and of hub gene (BIRC3) in different ccRCC cell types and cell lines, single-cell sequencing data was analysed and we performed Quantitative Real-time PCR to detect the expression of BIRC3 in ccRCC cell lines. Function of BIRC3 in ccRCC was assessed through Cell Counting Kit-8 (CCK8) assay (for proliferation), transwell and wound healing assays (for migration and invasion). Results Distinct necroptosis-related clusters exhibiting varying prognostic implications, and enrichment pathways were identified in ccRCC. A robust necroptosis-related model formulated based on the expression of six prognostic NRGs, presented substantial predictive capabilities of overall survival and was shown to be related with patients’ immune profiles, tumor mutation burden, and response to immunotherapy. Notably, the hub gene BIRC3 was markedly upregulated in both ccRCC tissues and cell lines, and showed significant correlations with immunosuppressive cells, immune checkpoints, and oncogenic pathways. Downregulation of BIRC3 demonstrated a negative regulatory effect on ccRCC cell proliferation migration and invasion. Conclusion The necroptosis-related model assumed a pivotal role in determining the prognosis, tumor mutation burden, immunotherapy response, and immune cell infiltration characteristics among ccRCC patients. BIRC3 exhibited significant correlations with the immunosuppressive microenvironment, which highlighted its potential for informing the design of innovative immunotherapies for ccRCC patients.

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Analyzing and validating the prognostic value and immune microenvironment of clear cell renal cell carcinoma

Cited by 10 publications

References 41 publications

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

Bioinformatics analysis and experimental validation of m6A and cuproptosis-related lncRNA NFE4 in clear cell renal cell carcinoma

Elevated ADH5 expression suggested better prognosis in kidney renal clear cell carcinoma (KIRC) and related to immunity through single-cell and bulk RNA-sequencing

Identification and validation of prognostic and tumor microenvironment characteristics of necroptosis index and BIRC3 in clear cell renal cell carcinoma

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