Dataset Information

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis.

ABSTRACT: Differential expression of TRPV1 has been detected in many cancer types, including clear cell renal cell carcinoma (ccRCC). However, the clinical significance of TRPV1 expression profile in ccRCC has not been comprehensively elucidated. In this study, TRPV1 expression in ccRCC and other cancer types was analyzed based on data from the GEO and Oncomine databases. Immunohistochemical (IHC) staining was performed for further validation in human ccRCC tissue chips. Survival and correlation analyses of TRPV1 were conducted using Kaplan-Meier Plotter (KM-Plotter) and the Tumor IMmune Estimation Resource (TIMER) database. TRPV1 exhibited a low expression profile in 2 GEO datasets (GSE6344, GSE36895) and 4 Oncomine datasets (Gumz, Lenburg, Beroukhim 1 and Beroukhim 2), as also confirmed by IHC staining. Survival analysis indicated that high enrichment of TRPV1 significantly predicted a better overall survival (OS) and disease-free survival (DFS) of 1, 3, 5 and 10 years in ccRCC patients. TIMER analysis showed that TRPV1 copy number alterations (CNA) were closely related to immune cell infiltration. The detailed results indicated that TRPV1 expression was positively correlated with the infiltration level of CD4+ T cells, but negatively correlated with B cells, macrophages, and dendritic cells infiltration. In addition, TRPV1 might also be inversely related to abundance of the regulatory T cells (Treg) and the M2 subset of macrophages. Finally, we found that TRPV1 expression was tightly associated with several key molecules of the classical pathways in ccRCC, such as VHL, TP53, HIF1A, MTOR, MAPK1, MET, CTNNB1, etc. Our research work suggests that TRPV1 is a novel tumor suppressor and prognosis marker for ccRCC and is of great value for further exploration.

SUBMITTER: Zheng L

PROVIDER: S-EPMC7477432 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis.

Zheng Long L Dou Xiaojie X Song Huijia H Gao Ruixia R Tang Xiaoshuang X

Journal of Cancer 20200725 19

Differential expression of TRPV1 has been detected in many cancer types, including clear cell renal cell carcinoma (ccRCC). However, the clinical significance of TRPV1 expression profile in ccRCC has not been comprehensively elucidated. In this study, TRPV1 expression in ccRCC and other cancer types was analyzed based on data from the GEO and Oncomine databases. Immunohistochemical (IHC) staining was performed for further validation in human ccRCC tissue chips. Survival and correlation analyses ...[more]

PMID: 32913462

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Project description:BackgroundPatients with advanced clear cell renal cell carcinoma (ccRCC) have a poor prognosis and lack effective prognostic biomarkers. N6-methyladenosine-related lncRNAs (m6A-related long noncoding RNAs [lncRNAs]) have been confirmed to be associated with the development of multiple tumors, but its role in ccRCC is not clear.MethodsGene expression data and clinical information of ccRCC patients were extracted from The Cancer Genome Atlas Database. The prognostic m6A-related lncRNAs were obtained by Pearson's correlation analysis and univariate Cox regression analysis. Afterward, the cluster classification and its correlation with prognosis, clinical characteristics, and immunity were analyzed. LASSO regression was used to establish the prognostic risk model. The predictive performance of the prognostic model was evaluated and validated by survival analysis and receiver operating characteristic curve analysis, et al. The expression of immune checkpoints and immune cell infiltration in patients with different risks were systematically analyzed.ResultsA total of 27 prognostic m6A-related lncRNAs were identified. These m6A-related lncRNAs were differentially expressed between tumor and normal tissues. Among them, 24 high-risk m6A-related lncRNAs were overexpressed in Cluster 2 and correlated with poor prognosis, low stromal score, high expression of immune checkpoints, and immunosuppressive cells infiltration. Based upon, a prognostic risk model composed of seven m6A-related lncRNAs was constructed. After a series of analyses, it was proved that this model had good sensitivity and specificity, and could predict the prognosis of patients with different clinical stratification. The expression of PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, and TIGIT were significantly increased in the high-risk patients, and there was a correlation between the risk score and immune cell infiltration.ConclusionsThe seven m6A-related lncRNAs prognostic risk signature showed reliable prognostic predictive power for ccRCC and was associated with the expression of immune checkpoints and immune cell infiltration. This seven m6A-related lncRNAs signature will be helpful in managing ccRCC and guiding individualized immunotherapy.

Project description:Background Kidney renal clear cell carcinoma (KIRC) is a malignant tumor with a high degree of immune infiltration. Identifying immune biomarkers is essential for the treatment of KIRC. Studies have identified the potential of NEIL3 to modulate the immune microenvironment and promote tumor progression. However, the role of NEIL3 in KIRC remains uncertain. This study was to investigate the effect of NEIL3 on the prognosis and immune infiltration of patients with KIRC. Methods TCGA and GEO databases were used to study the expression of NEIL3 in KIRC. Cox regression analysis was used to examine the relationship between the expression of NEIL3 and clinicopathological variables and survival. Furthermore, Gene Set Cancer Analysis (GSCA) was applied to study the impact of NEIL3 methylation on outcomes of KIRC. Through gene ontology (GO) and Gene set enrichment (GSEA) analysis, the biological processes and signal pathways related to NEIL3 expression were identified. In addition, immune infiltration analysis was conducted via CIBERSORT analysis, ssGSEA analysis and TISIDB database. Results NEIL3 was overexpressed in KIRC, and it was significantly related with histologic grade, pathologic stage, T stage, M stage, and vital status of KIRC patients (P < 0.001). The expression of NEIL3 was associated with worse outcomes. Univariate and multivariate Cox analysis showed that NEIL3 may be an indicator of adverse outcomes in KIRC. GSEA analysis revealed that NEIL3 may be involved in signal pathways including cell cycle, DNA replication, mismatch repair, P53 signal pathway, and antigen processing and presentation. In addition, immune infiltration analysis showed a positive correlation between NEIL3 expression and multiple immune cells (activated CD8 T cells, activated dendritic cells, myeloid-derived suppressor cells, follicular helper T cells, and regulatory T cells) and immunoinhibitors (PD1, CTLA4, LAG3, TIGHT, IL10, and CD96). Conclusion NEIL3 is a potential independent biomarker of KIRC, which is relevant to immune infiltration.

Dataset Information

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis.

Publications

TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis.

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