Identification of a Novel Defined Immune-Autophagy-Related Gene Signature Associated With Clinical and Prognostic Features of Kidney Renal Clear Cell Carcinoma

Background: As a common cancer of the urinary system in adults, renal clear cell carcinoma is metastatic in 30% of patients, and 1–2 years after diagnosis, 60% of patients die. At present, the rapid development of tumor immunology and autophagy had brought new directions to the treatment of renal cancer. Therefore, it was extremely urgent to find potential targets and prognostic biomarkers for immunotherapy combined with autophagy.Methods: Through GSE168845, immune-related genes, autophagy-related genes, and immune-autophagy-related differentially expressed genes (IAR-DEGs) were identified. Independent prognostic value of IAR-DEGs was determined by differential expression analysis, prognostic analysis, and univariate and multivariate Cox regression analyses. Then, the lasso Cox regression model was established to evaluate the correlation of IAR-DEGs with the immune score, immune checkpoint, iron death, methylation, and one-class logistic regression (OCLR) score.Results: In this study, it was found that CANX, BID, NAMPT, and BIRC5 were immune-autophagy-related genes with independent prognostic value, and the risk prognostic model based on them was well constructed. Further analysis showed that CANX, BID, NAMPT, and BIRC5 were significantly correlated with the immune score, immune checkpoint, iron death, methylation, and OCLR score. Further experimental results were consistent with the bioinformatics analysis.Conclusion: CANX, BID, NAMPT, and BIRC5 were potential targets and effective prognostic biomarkers for immunotherapy combined with autophagy in kidney renal clear cell carcinoma.

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GALNT14 expression in renal clear cell carcinoma and its effect on prognosis

10.21203/rs.3.rs-761157/v1 ◽

2021 ◽

Author(s):

Yuqin Wei ◽

Fan Wu ◽

Shengfeng Zhang ◽

Yanlin Tan ◽

Qunying Wu ◽

...

Keyword(s):

Cell Carcinoma ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Regulatory Pathways ◽

Cox Analysis ◽

The Relationship

Abstract Background The expression of GALNT14 in kidney renal clear cell carcinoma (KIRC) and its clinical significance remains unknown. Methods The KIRC data expressed by GALNT14 was downloaded from The Cancer Genome Atlas (TCGA) database. The expression of GALNT14 was analyzed by R software, Perl software and online analysis database. The relationship between GALNT14 expression and clinicopathological features in KIRC was analyzed by univariate, multivariate Cox regression and some databases. Gene Expression Profling Interactive Analysis (GEPIA), Starbase v3.0, UALCAN, and Kaplan-Meier were used to analyze the relationship between GALNT14 expression and overall survival (OS) in KIRC. UALCAN detects the expression of GALNT14 methylation in KIRC. Linkedomics and Genemania were used to analyze the gene co-expression of GALNT14. Gene Set Enrichment Analysis (GSEA) was performed to search for potential regulatory pathways. Results We found that GALNT14 was overexpressed in KIRC (p=1.433e-25). Patients with high GALNT14 expression in KIRC had a better prognosis than patients with low GALNT14 expression (p=0.008). In addition, high GALNT14 expression in KIRC was significantly associated with low T stage and positive OS (p<0.05). Univariate Cox analysis showed that GALNT14 was positively correlated with OS (p<0.001). Multivariate Cox analysis showed that GALNT14 was associated with OS (p<0.001), age (p=0.01) and histological grade (p=0.02). GALNT14 methylation is low expressed in KIRC (p<0.001). GSEA analysis showed that GALNT14 was enriched in histidine metabolism, peroxisome, and renin-angiotensin system pathways. Conclusion GALNT14 can be used as an independent prognostic factor for renal clear cell carcinoma and a potential target for clinical diagnosis and treatment of KIRC.

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PROGNOSTIC VALUE OF CARBONIC ANHYDRASE IX AND KI67 AS PREDICTORS OF SURVIVAL FOR RENAL CLEAR CELL CARCINOMA

The Journal of Urology ◽

10.1097/01.ju.0000116444.08690.e2 ◽

2004 ◽

Vol 171 (6 Part 1) ◽

pp. 2461-2466 ◽

Cited By ~ 116

Author(s):

MATTHEW H.T. BUI ◽

HARRI VISAPAA ◽

DAVID SELIGSON ◽

HYUNG KIM ◽

KEN-RYU HAN ◽

...

Keyword(s):

Carbonic Anhydrase ◽

Cell Carcinoma ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Carbonic Anhydrase Ix

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Identification of the Prognosis Value and Potential Mechanism of Immune Checkpoints in Renal Clear Cell Carcinoma Microenvironment

Frontiers in Oncology ◽

10.3389/fonc.2021.720125 ◽

2021 ◽

Vol 11 ◽

Author(s):

Guodong Liao ◽

Ping Wang ◽

Yuyong Wang

Keyword(s):

Immune Checkpoint ◽

Prognostic Value ◽

Immune Cell ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Immune Checkpoints ◽

Immune Cell Infiltration ◽

Free Survival ◽

Checkpoint Genes

BackgroundKidney Renal Clear Cell Carcinoma (KIRC) is one of the most prevalent types of cancer worldwide. KIRC has a poor prognosis and, to date, immunotherapy based on immune checkpoints is the most promising treatment. However, the role of immune checkpoints in KIRC remains ambiguous.MethodsBioinformatics analyses and qRT-PCR were performed to explore and further confirm the prognostic value of immune checkpoint genes and their correlation with immune infiltration in KIRC samples.ResultsThe expression of the immune checkpoint genes CD274, PDCD1LG2, HAVCR2, CTLA4, TIGFT, LAG3, and PDCD1 was upregulated in KIRC tissues. These genes were involved in the activation of the apoptosis pathway in KIRC. Low expression of CD274 and HAVCR2 and high expression of CTLA4 were associated with poor overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of KIRC patients. The univariate and multivariate analyses revealed that CTLA4, HAVCR2, age, pTNM stage, and tumor grade were independent factors affecting the prognosis of KIRC patients. A predictive nomogram demonstrated that the calibration plots for the 3‐year and 5‐year OS probabilities showed good agreement compared to the actual OS of KIRC patients. The expression of CTLA4 and HAVCR2 were positively associated with immune cell infiltration, immune biomarkers, chemokines, and chemokine receptors. Moreover, miR-20b-5p was identified as a potential miRNA target of CTLA4 in KIRC.ConclusionOur study clarified the prognostic value of several immune checkpoint regulators in KIRC, revealing a CTLA4/miR-20b-5p axis in the control of immune cell infiltration in the tumor microenvironment.

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NCF1/2/4 Are Prognostic Biomarkers Related to the Immune Infiltration of Kidney Renal Clear Cell Carcinoma

BioMed Research International ◽

10.1155/2021/5954036 ◽

2021 ◽

Vol 2021 ◽

pp. 1-31

Author(s):

Yifei Chen ◽

Fei He ◽

Ruhua Wang ◽

Menglin Yao ◽

Yarui Li ◽

...

Keyword(s):

Cell Carcinoma ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Genetic Alterations ◽

Renal Clear Cell Carcinoma ◽

Prognostic Biomarkers ◽

Mrna Levels ◽

Poor Overall Survival ◽

Cytoplasmic Factor ◽

Value Analysis

Neutrophil cytoplasmic factor 1/2/4 (NCF1/2/4) belongs to the NADPH oxidase complex, which is a cytoplasmic component, and its polymorphism is the main factor related to autoimmune diseases, which is probably caused by the regulation of peroxide. They also play a role in tumor growth and metastasis. This research is aimed at evaluating the biological function and prognostic role of NCF1, NCF2, and NCF4 genes in kidney renal clear cell carcinoma (KIRC) by using multiple online bioinformatics website, including Oncomine, GEPIA, UALCAN, Kaplan–Meier Plotter, TIMER, TISIDB, cBioPortal, LinkedOmics, GeneMANIA, and DAVID databases. The mRNA levels of NCFs were higher in KIRC tissues than in normal tissues. The overexpression of NCFs was significantly correlated with advanced pathological grades and individual cancer stages in KIRC. Meanwhile, the expressions of NCFs played an important role in the tumorigenesis and progression of KIRC. Prognostic value analysis suggested that high transcription levels of NCF1/4 were associated with poor overall survival in KIRC patients. In addition, results from the LinkedOmics database showed that the KEGG pathway related to NCFs mainly focused on immune activation and immune regulation function. NCF genetic alterations, including copy number amplification, missense mutation, and deep deletion, could be found through the cBioPortal database. Further, NCF expression was significantly correlated with infiltration levels of various immune cells as well as immune signatures. Protein-protein interaction network and enrichment analysis of NCF1/2/4 in KIRC showed that NCF coexpressed genes mainly associated with diverse immune marker sets showed significance. Overall, these results indicated that NCFs could be prognostic biomarkers as well as effective targets for diagnosis in KIRC.

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The prognostic value and immunological role of the small mother against decapentaplegic proteins in kidney renal clear cell carcinoma

Translational Cancer Research ◽

10.21037/tcr-21-178 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Siyue Zhang ◽

Zhuang Liu ◽

Mingming Xiao ◽

Hong Liu

Keyword(s):

Cell Carcinoma ◽

Prognostic Value ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma

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Integrated analysis of the underlying immunomodulator and survival signature of STON1 gene in kidney renal clear cell carcinoma

10.21203/rs.3.rs-847345/v1 ◽

2021 ◽

Author(s):

Axiu Zheng ◽

Jianrong Bai ◽

Yanping Ha ◽

Bingshu Wang ◽

Yuan Zou ◽

...

Keyword(s):

Cell Carcinoma ◽

Risk Score ◽

Immune Cell ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Clinicopathological Characteristics ◽

Risk Scores ◽

Integrated Analysis

Abstract Background Stonin 1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of a series of public databases to determine the expression and clinical significance of STON1 in KIRC and focused on STON1-related immunomodulator and survival signatures. A nomogram model integrating clinicopathological characteristics and risk scores for KIRC was established and validated. Results Through TGCA and GEO databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis, and vital status of KIRC. Furthermore, OncoLnc, UALCAN, Kaplan–Meier, and GEPIA2 analyses supported that KIRC patients with high STON1 expression had better overall survival. STON1 was positively associated with mismatch proteins including MLH1, PMS2, MSH2, MSH6 and EpCAM, and was negatively correlated with tumor mutational burden. Interestingly, arm-level deletion of STON1 was clearly related to the abundance of immune cells and the infiltration abundance in the majority of 26 immune cell types that were positively related to STON1 mRNA level in the TIMER database. The TISIDB database revealed 21 immunostimulators and 10 immunoinhibitors that were obviously related to STON1 in KIRC. In univariate and multivariate Cox regression analyses, CTLA4 , KDR , LAG3 , PDCD1 , HHLA2 , TNFRSF25 , and TNFSF14 were screened to establish a risk score model, and the low-risk group had a better prognosis for KIRC. Furthermore, a nomogram integrating clinicopathological characteristics and risk score had better accuracy and practicability in predicating the survival of KIRC patients. Conclusions Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, loss of STON1 is associated with the aberrant immune microenvironment in KIRC. Integrated clinicopathological characteristics and risk score derived from STON1 -related immunomodulators can aid the prediction of KIRC survival.

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Analyzing and Validating the Prognostic Value of a TNF-Related Signature in Kidney Renal Clear Cell Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.689037 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wenhao Zhang ◽

Changjiu Li ◽

Fanding Wu ◽

Ning Li ◽

Yuwei Wang ◽

...

Keyword(s):

Cell Carcinoma ◽

Prognostic Value ◽

T Regulatory Cells ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Risk Groups ◽

Renal Clear Cell Carcinoma ◽

Risk Scores ◽

Immune Infiltration ◽

Mutation Burden

Background: Kidney renal clear cell carcinoma (KIRC) has the highest incidence rate in renal cell carcinoma (RCC). Although bioinformatics is widely used in cancer, few reliable biomarkers of KIRC have been found. Therefore, continued efforts are required to elucidate the potential mechanism of the biogenesis and progression of KIRC.Methods: We evaluated the expression of tumor necrosis factor (TNF) family genes in KIRC, and constructed a prognostic signature. We validated the signature by another database and explored the relationship between the signature and progression of KIRC. We assessed the prognostic value, immune infiltration, and tumor mutation burden (TMB) of the signature in KIRC.Results: We selected four key genes (TNFSF14, TNFRSF19, TNFRSF21, and EDA) to construct the TNF-related signature. We divided the KIRC patients into high- and low-risk groups based on the signature. Patients with higher risk scores had shorter overall survival and worse prognosis. With another database, we validated the value of the signature. The signature was considered as an independent risk factor. A higher level of risk score was relevant to higher level of immune infiltration, especially T regulatory cells, CD8+ T cells, and macrophages. The signature was also associated with TMB scores, and it may have an effect on assessing the efficacy of immunotherapy.Conclusion: This is the first TNF-family-related signature of KIRC and we demonstrated its effectiveness. It played a significant role in predicting the prognosis of patients with KIRC. It also has the potential to become a powerful tool in guiding the immunotherapy of KIRC patients in clinical practice.

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Identification of a Prognostic Risk Signature of Kidney Renal Clear Cell Carcinoma Based on Regulating the Immune Response Pathway Exploration

Journal of Oncology ◽

10.1155/2020/6657013 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Guangzhen Wu ◽

Yingkun Xu ◽

Chenglin Han ◽

Zilong Wang ◽

Jiayi Li ◽

...

Keyword(s):

Immune Response ◽

Cell Carcinoma ◽

Sensitivity And Specificity ◽

Cox Regression ◽

Clear Cell ◽

Clear Cell Carcinoma ◽

Renal Clear Cell Carcinoma ◽

Lasso Regression ◽

Regression Curve ◽

Cox Regression Analysis

Purpose. To construct a survival model for predicting the prognosis of patients with kidney renal clear cell carcinoma (KIRC) based on gene expression related to immune response regulation. Materials and Methods. KIRC mRNA sequencing data and patient clinical data were downloaded from the TCGA database. The pathways and genes involved in the regulation of the immune response were identified from the GSEA database. A single factor Cox analysis was used to determine the association of mRNA in relation to patient prognosis P < 0.05 . The prognostic risk model was further established using the LASSO regression curve. The survival prognosis model was constructed, and the sensitivity and specificity of the model were evaluated using the ROC curve. Results. Compared with normal kidney tissues, there were 28 dysregulated mRNA expressions in KIRC tissues P < 0.05 . Univariate Cox regression analysis revealed that 12 mRNAs were related to the prognosis of patients with renal cell carcinoma. The LASSO regression curve drew a risk signature consisting of six genes: TRAF6, FYN, IKBKG, LAT2, C2, IL4, EREG, TRAF2, and IL12A. The five-year ROC area analysis (AUC) showed that the model has good sensitivity and specificity (AUC >0.712). Conclusion. We constructed a risk prediction model based on the regulated immune response-related genes, which can effectively predict the survival of patients with KIRC.

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