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

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.

scholarly journals SIRT7 is a prognostic biomarker in kidney renal clear cell carcinoma that is correlated with immune cell infiltration

2021 ◽  
Author(s):  
Ming Li ◽  
Yue Qian ◽  
Lili Mu ◽  
Yixian Wang ◽  
Xue Jin ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Roc Curve ◽  
Functional Role ◽  
Immune Cell ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Cancer Type ◽  
Immune Cell Infiltration

Abstract Background: SIRT7 has been shown to be expressed in many cancer types, including kidney renal clear cell carcinoma (KIRC), but its functional role in this oncogenic context remains to be firmly defined. This study was designed to explore correlations between SIRT7 and KIRC characteristics using the TCGA database. Methods: Relationships between SIRT7 expression and KIRC patient clinicopathological characteristics were assessed through Kruskal-Wallis tests, Wilcoxon signed-rank tests, and logistic regression analyses. Area under the ROC curve (AUC) values were used to assess the prognostic value of SIRT7 as a means of classifying KIRC patients. The functional role of SIRT7 in this cancer type was assessed through GO/KEGG enrichment analyses and immune cell infiltration analyses. Results: In KIRC patients, higher levels of SIRT7 expression were associated with Race, M stage, T stage (all P < 0.05). SIRT7 offered significant diagnostic value in ROC curve analyses (AUC = 0.912), and elevated SIRT7 levels were linked to worse patient overall survival (OS; P < 0.001). The expression of SIRT7 was independently related with KIRC patient OS (HR: 1.827; 95%CI: 1.346-2.481; P<0.001). In GO/KEGG analyses, SIRT7 was found to be associated with ubiquitin-mediated proteolysis and nucleotide excision repair. Higher SIRT7 expression was related to the enhanced infiltration of certain immune cells.Conclusions: Increased SIRT7 expression was associated with a worse KIRC patient prognosis, and immune infiltrates, suggesting it may offer value as a prognostic biomarker for this cancer type.

scholarly journals Identification a ceRNA (XIST/miR-10a-5p/SERPINE1) Axis as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma.

2021 ◽  
Author(s):  
Rui-ji Liu ◽  
Zhi-Peng Xu ◽  
Shuying Li ◽  
Jun-Jie Yu ◽  
Bin Xu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Carcinoma ◽  
Immune Cell ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Cerna Network

Abstract Background: Kidney cancer is one of the most common malignancies, of which the most aggressive subtype was kidney renal clear cell carcinoma (KIRC), accounting for 80% of them. A growing number of studies point to the involvement of competitive endogenous RNAs in tumor development. However, the role of ceRNA network involved in KIRC remains unclear. Thus, the aim of this study was to investigate the BAP1-associated prognostic ceRNA in KIRC. Methods: We downloaded the RNAseq data from TCGA along with the relevant clinical data. We screened the differentially expressed lncRNAs, miRNAs, mRNAs according to the expression of BAP1 and established a ceRNA network. Results: After comprehensive bioinformatics analysis, we identified the XIST-miR-10a-5p-SERPINE1 ceRNA axis. Next, we confirmed the prognostic role of miR-10a-5p/SERPINE1 in KIRC using survival analysis and Cox regression analysis. To investigate the abnormally high expression of SERPINE1, we performed methylation analysis of SERPINE1 and concluded that the methylation level of SERPINE1 in KIRC was significantly lower than that in normal tissues. Furthermore, to study the role of SERPINE1 in the immune microenvironment in KIRC, we performed immune cell infiltration analysis and found that SERPINE1 expression was positively correlated with the level of multiple immune cell infiltration (CD 4+ T cell, CD 8+ T cell, macrophages, dendritic cells, neutrophils). Conclusion: We constructed a ceRNA (XIST/has-miR-10a-5p/SERPINE1) that can be used as prognostic biomarker of KIRC. Furthermore, we found that miR-10a-5p/SERPINE1 were significantly associated with clinical features and were independent prognostic factors of KIRC.

scholarly journals SIRT7 is a prognostic biomarker in kidney renal clear cell carcinoma that is correlated with immune cell infiltration

2021 ◽  
Author(s):  
Wei Zhang ◽  
Yue Qian ◽  
Xue Jin ◽  
Yixian Wang ◽  
Lili Mu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Roc Curve ◽  
Functional Role ◽  
Immune Cell ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Cancer Type ◽  
Immune Cell Infiltration

Abstract Background: SIRT7 has been shown to be expressed in many cancer types, including kidney renal clear cell carcinoma (KIRC), but its functional role in this oncogenic context remains to be firmly defined. This study was designed to explore correlations between SIRT7 and KIRC characteristics using the TCGA database. Methods: Relationships between SIRT7 expression and KIRC patient clinicopathological characteristics were assessed through Kruskal-Wallis tests, Wilcoxon signed-rank tests, and logistic regression analyses. Area under the ROC curve (AUC) values were used to assess the prognostic value of SIRT7 as a means of classifying KIRC patients. The functional role of SIRT7 in this cancer type was assessed through GO/KEGG enrichment analyses and immune cell infiltration analyses. Results: In KIRC patients, higher levels of SIRT7 expression were associated with Race, M stage, T stage (all P < 0.05). SIRT7 offered significant diagnostic value in ROC curve analyses (AUC = 0.912), and elevated SIRT7 levels were linked to worse patient overall survival (OS; P < 0.001). The expression of SIRT7 was independently related with KIRC patient OS (HR: 1.827; 95%CI: 1.346-2.481; P<0.001). In GO/KEGG analyses, SIRT7 was found to be associated with ubiquitin-mediated proteolysis and nucleotide excision repair. Higher SIRT7 expression was related to the enhanced infiltration of certain immune cells.Conclusions: Increased SIRT7 expression was associated with a worse KIRC patient prognosis, and immune infiltrates, suggesting it may offer value as a prognostic biomarker for this cancer type.

scholarly journals SIRT7 is a prognostic biomarker in kidney renal clear cell carcinoma that is correlated with immune cell infiltration

2022 ◽  
Author(s):  
Wei Zhang ◽  
Yue Qian ◽  
Xue Jin ◽  
Yixian Wang ◽  
Lili Mu
Keyword(s):  
Cell Carcinoma ◽  
Roc Curve ◽  
Functional Role ◽  
Immune Cell ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Cancer Type ◽  
Immune Cell Infiltration

Abstract Background: SIRT7 has been shown to be expressed in many cancer types, including kidney renal clear cell carcinoma (KIRC), but its functional role in this oncogenic context remains to be firmly defined. This study was designed to explore correlations between SIRT7 and KIRC characteristics using the TCGA database. Methods: Relationships between SIRT7 expression and KIRC patient clinicopathological characteristics were assessed through Kruskal-Wallis tests, Wilcoxon signed-rank tests, and logistic regression analyses. Area under the ROC curve (AUC) values were used to assess the prognostic value of SIRT7 as a means of classifying KIRC patients. The functional role of SIRT7 in this cancer type was assessed through GO/KEGG enrichment analyses and immune cell infiltration analyses. Results: In KIRC patients, higher levels of SIRT7 expression were associated with Race, M stage, T stage (all P < 0.05). SIRT7 offered significant diagnostic value in ROC curve analyses (AUC = 0.912), and elevated SIRT7 levels were linked to worse patient overall survival (OS; P < 0.001). The expression of SIRT7 was independently related with KIRC patient OS (HR: 1.827; 95%CI: 1.346-2.481; P<0.001). In GO/KEGG analyses, SIRT7 was found to be associated with ubiquitin-mediated proteolysis and nucleotide excision repair. Higher SIRT7 expression was related to the enhanced infiltration of certain immune cells.Conclusions: Increased SIRT7 expression was associated with a worse KIRC patient prognosis, and immune infiltrates, suggesting it may offer value as a prognostic biomarker for this cancer type.

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

2021 ◽  
Vol 8 ◽  
Author(s):  
Guangyuan Zhang ◽  
Lei Zhang ◽  
Si Sun ◽  
Ming Chen
Keyword(s):  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Prognostic Value ◽  
Cox Regression ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Prognostic Biomarkers ◽  
Prognostic Features ◽  
Immune Score

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.

scholarly journals Identification of TRPM2 as a Marker Associated With Prognosis and Immune Infiltration in Kidney Renal Clear Cell Carcinoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Lei Sun ◽  
Zijun Zhang ◽  
Hang Zhao ◽  
Miaoyun Qiu ◽  
Ying Wen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Carcinoma ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Immune Infiltration

TRPM2 (transient receptor potential melastatin-2), a Ca2+ permeable, non-selective cation channel, is highly expressed in cancers and regulates tumor cell migration, invasion, and proliferation. However, no study has yet demonstrated the association of TRPM2 with the prognosis of cancer patients or tumor immune infiltration, and the possibility and the clinical basis of TRPM2 as a prognostic marker in cancers are yet unknown. In the current study, we first explored the correlation between the mRNA level of TRPM2 and the prognosis of patients with different cancers across public databases. Subsequently, the Tumor Immune Estimation Resource (TIMER) platform and the TISIDB website were used to assess the correlation between TRPM2 and tumor immune cell infiltration level. We found that 1) the level of TRPM2 was significantly elevated in most tumor tissues relative to normal tissues; 2) TRPM2 upregulation was significantly associated with adverse clinical characteristics and poor survival of kidney renal clear cell carcinoma (KIRC) patients; 3) the level of TRPM2 was positively related to immune cell infiltration. Moreover, TRPM2 was closely correlated to the gene markers of diverse immune cells; 4) a high TRPM2 expression predicted worse prognosis in KIRC based on different enriched immune cell cohorts; and 5) TRPM2 was mainly implemented in the T-cell activation process indicated by Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. In conclusion, TRPM2 can serve as a marker to predict the prognosis and immune infiltration in KIRC through the regulation of T-cell activation. The current data may provide additional information for further studies surrounding the function of TRPM2 in KIRC.

scholarly journals Reclassification of Kidney Clear Cell Carcinoma Based on Immune Cell Gene-Related DNA CpG Pairs

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 215
Author(s):  
Qizhan Luo ◽  
Thomas-Alexander Vögeli
Keyword(s):  
Cell Carcinoma ◽  
Immune Cell ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Pairwise Comparison ◽  
Clinicopathological Features ◽  
Immune Checkpoints ◽  
Potential Mechanism ◽  
Tissue Samples

Background: A new method was developed based on the relative ranking of gene expression level, overcoming the flaw of the batch effect, and having reliable results in various studies. In the current study, we defined the two methylation sites as a pair. The methylation level in a specific sample was subject to pairwise comparison to calculate a score for each CpGs-pair. The score was defined as a CpGs-pair score. If the first immune-related CpG value was higher than the second one in a specific CpGs-pair, the output score of this immune-related CpGs-pair was 1; otherwise, the output score was 0. This study aimed to construct a new classification of Kidney Clear Cell Carcinoma (KIRC) based on DNA CpGs (methylation sites) pairs. Methods: In this study, the biomarkers of 28 kinds of immune infiltration cells and corresponding methylation sites were acquired. The methylation data were compared between KIRC and normal tissue samples, and differentially methylated sites (DMSs) were obtained. Then, DNA CpGs-pairs were obtained according to the pairs of DMSs. In total, 441 DNA CpGs-pairs were utilized to construct a classification using unsupervised clustering analysis. We also analyzed the potential mechanism and therapy of different subtypes, and validated them in a testing set. Results: The classification of KIRC contained three subgroups. The clinicopathological features were different across three subgroups. The distribution of immune cells, immune checkpoints and immune-related mechanisms were significantly different across the three clusters. The mutation and copy number variation (CNV) were also different. The clinicopathological features and potential mechanism in the testing dataset were consistent with those in the training set. Conclusions: Our findings provide a new accurate and stable classification for developing personalized treatments for the new specific subtypes.

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