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

Author(s):  
Wei Zhang ◽  
Yue Qian ◽  
Xue Jin ◽  
Yixian Wang ◽  
Lili Mu

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.

2021 ◽  
Author(s):  
Ming Li ◽  
Yue Qian ◽  
Lili Mu ◽  
Yixian Wang ◽  
Xue Jin ◽  
...  

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.


2021 ◽  
Author(s):  
Wei Zhang ◽  
Yue Qian ◽  
Xue Jin ◽  
Yixian Wang ◽  
Lili Mu ◽  
...  

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.


2021 ◽  
Author(s):  
Rui-ji Liu ◽  
Zhi-Peng Xu ◽  
Shuying Li ◽  
Jun-Jie Yu ◽  
Bin Xu ◽  
...  

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.


2022 ◽  
Vol 8 ◽  
Author(s):  
Lei Sun ◽  
Zijun Zhang ◽  
Hang Zhao ◽  
Miaoyun Qiu ◽  
Ying Wen ◽  
...  

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zhuolun Sun ◽  
Changying Jing ◽  
Xudong Guo ◽  
Mingxiao Zhang ◽  
Feng Kong ◽  
...  

Kidney renal clear cell carcinoma (KIRC) has long been identified as a highly immune-infiltrated tumor. However, the underlying role of pyroptosis in the tumor microenvironment (TME) of KIRC remains poorly described. Herein, we systematically analyzed the prognostic value, role in the TME, response to ICIs, and drug sensitivity of pyroptosis-related genes (PRGs) in KIRC patients based on The Cancer Genome Atlas (TCGA) database. Cluster 2, by consensus clustering for 24 PRGs, presented a poor prognosis, likely because malignancy-related hallmarks were remarkably enriched. Additionally, we constructed a prognostic prediction model that discriminated well between high- and low-risk patients and was further confirmed in external E-MTAB-1980 cohort and HSP cohort. By further analyzing the TME based on the risk model, higher immune cell infiltration and lower tumor purity were found in the high-risk group, which presented a poor prognosis. Patients with high risk scores also exhibited higher ICI expression, indicating that these patients may be more prone to profit from ICIs. The sensitivity to anticancer drugs that correlated with model-related genes was also identified. Collectively, the pyroptosis-related prognosis risk model may improve prognostic information and provide directions for current research investigations on immunotherapeutic strategies for KIRC patients.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Hang Xu ◽  
Xiaonan Zheng ◽  
Shiyu Zhang ◽  
Xianyanling Yi ◽  
Tianyi Zhang ◽  
...  

AbstractCurrent treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination.


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