Dataset Information

PTPRO predicts patient prognosis and correlates with immune infiltrates in human clear cell renal cell carcinoma

ABSTRACT:

Background

The tumor-suppressive role of protein tyrosine phosphatase receptor type O (PTPRO) has been described in a variety of human cancers; however, the clinical significance of PTPRO in human clear cell renal cell carcinoma (ccRCC) remains unclear.

Methods

PTPRO expression in renal cell carcinoma (RCC) was analyzed via the Oncomine database, Gene Expression Omnibus (GEO) datasets, and The Cancer Genome Atlas (TCGA) datasets. The Kaplan-Meier curves and Cox proportional hazards model were used to evaluate the relationship of PTPRO with overall survival in ccRCC. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed to explore the signaling pathways in which PTPRO may be involved. The correlation between PTPRO and immune infiltrates in ccRCC was investigated via Tumor Immune Estimation Resource (TIMER) database. The association between PTPRO mRNA expression and its methylation in RCC was analyzed using the Cancer Cell Line Encyclopedia (CCLE) dataset, GEO dataset, and cBioPortal database. The impact of PTPRO methylation on overall survival was estimated by the MethSurv database.

Results

We showed that the expression of PTPRO was significantly lower in human RCC. Moreover, the lower expression of PTPRO was associated with worse overall survival in ccRCC, particularly in the advanced stage patients. Multivariate Cox regression analysis revealed the expression of PTPRO as an independent prognostic predictor for overall survival of ccRCC. Of note, PTPRO was found to be associated with the activation of immune signaling and immune cell infiltration. Furthermore, methylation of PTPRO was prevalently observed in ccRCC, and methylation of PTPRO predicted the poor outcome of ccRCC.

Conclusions

Our findings suggested that PTPRO at both RNA and DNA methylation levels had the potential as a prognostic biomarker for predicting prognosis, and PTPRO expression was closely associated with immune infiltration in ccRCC patients.

SUBMITTER: Gan J

PROVIDER: S-EPMC8798001 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background: Petite Integration Factor 1 (PIF1) is a multifunctional helicase and DNA processing enzyme that plays an important role in the process of several cancer types. However, the relationship between clear cell renal cell carcinoma (ccRCC) and PIF1 remains unclear. This study aims to explore the role of PIF1 in ccRCC tumorigenesis and prognosis. Methods: Based on The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, we retrieved and verified the expression of PIF1 in ccRCC tissues as well as normal tissues. To assess the protein expression of PIF1 by using the Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). We also performed receiver operating characteristic (ROC) curve analysis to differentiate the effectiveness of PIF1 in ccRCC and adjacent normal tissues. To evaluate the value of PIF1 on clinical outcomes in ccRCC patients by using multivariate methods and Kaplan‒Meier survival curves. Protein‒protein interaction (PPI) networks were made with STRING. We determined the relationship between the expression of PIF1 and immune cell infiltration with single-sample gene set enrichment analysis (ssGSEA). Results: Compared with normal tissues, the expression of PIF1 was significantly elevated in ccRCC. The mRNA expression of PIF1 is correlated with high TNM stage and high pathologic stage. The receiver operating characteristic (ROC) curve analysis showed that PIF1 was related to an area under the curve (AUC) value of 0.928 to distinguish between ccRCC tissues and normal tissues. Kaplan‒Meier survival analysis showed that the overall survival (OS) of ccRCC patients with a high level of PIF1 was significantly shorter than that of those with a low level of PIF1. PIF1 may play an important role in the occurrence of tumors. Correlation analysis showed that PIF1-mediated carcinogenesis may participate in the process of tumor immune escape in ccRCC. Conclusion: PIF1 could be a reference biomarker to identify ccRCC patients with poor prognosis. PIF1 may play a distinct role in the microenvironment of ccRCC by regulating tumor infiltration of immune cells, which is a new therapeutic target to affect the growth of the tumor.

Project description:Gasdermin B (GSDMB) is part of the gasdermin (GSDM) family, and they use varying means of domain interactions in molecules to adjust their pore-forming and lipid-binding actions. The GSDM family has roles in the regulation of cell differentiation and proliferation, particularly in the process of pyroptosis. Nonetheless, the correlation of GSDMB with immune infiltrates and its prognostic values in clear cell renal cell carcinoma (ccRCC) are still undefined. Therefore, we assessed the correlation of GSDMB with immune infiltrates and its prognostic role in ccRCC. The transcriptional expression profiles of GSDMB in ccRCC tissues in addition to normal tissues were retrieved from The Cancer Genome Atlas (TCGA) and additionally verified in a different independent cohort, which was obtained from the Gene Expression Omnibus (GEO) database. The Human Protein Atlas and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to assess the protein expression of GSDMB. To assess the effectiveness of GSDMB in distinguishing ccRCC from normal samples, the receiver operating characteristic (ROC) curve analysis was performed. Relationships between GSDMB expression, clinicopathological variables, and overall survival (OS) were evaluated with multivariate methods as well as Kaplan-Meier survival curves. Protein-protein interaction (PPI) networks were created with STRING. Functional enrichment analyses were conducted by utilizing the "ClusterProfiler" package. The Tumor Immune Estimation Resource (TIMER) and tumor-immune system interaction database (TISIDB) were utilized to determine the association between the mRNA expression of GSDMB and immune infiltrates. GSDMB expression was significantly more upregulated in ccRCC tissues compared to surrounding normal tissues. An increase in the mRNA expression of GSDMB was related to the high pathologic stage and advanced TNM stage. The analysis of the ROC curve indicated that GSDMB had an AUC value of 0.820 to distinguish between ccRCC tissues and adjacent normal controls. Kaplan-Meier survival analysis indicated that ccRCC patients with high GSDMB had a poorer prognosis compared to those with low GSDMB (P < 0.001). Correlation analysis showed that the mRNA expression of GSDMB was associated with immune infiltrates and the purity of the tumor. Upregulation of GSDMB is significantly related to immune infiltrates and poor survival in ccRCC. The results of this study indicate that GSDMB could be regarded as a biomarker for the detection of poor prognosis and potential target of immune treatment in ccRCC.

Project description:Background: Clear cell renal cell carcinoma (ccRCC) constitutes the commonest kidney malignancy. Immunogenic cell death (ICD) is a type of regulated cell death (RCD), which sufficiently activates adaptive immunity. However, ICD's involvement in cancer development is unclear, as well as the associations of ICD effectors with ccRCC prognosis. Methods: RNA-sequencing expression profiles of ccRCC in The Cancer Genome Atlas (TCGA) and normal samples in Gene Expression Omnibus (GEO) were comprehensively investigated. Consensus clustering analysis was employed to determine subgroup members linked to ICD-related genes. Functional enrichment analysis was utilized for the examination of TLR4's biological role, and in vitro cellular assays were utilized for further confirmation. We also used Kaplan-Meier (KM) and Cox regression analyses to assess TLR4's prognostic value. Finally, "CIBERSORT" was employed for immune score evaluation. Results: The associations of ICD effectors with ccRCC prognosis were examined based on TCGA, and 12 genes showed upregulation in ccRCC tissue specimens. Meanwhile, ccRCC cases with upregulated ICD-related genes had increased overall survival. Among these ICD-related genes, TLR4 was selected for subsequent analysis. TLR4 was upregulated in ccRCC samples and independently predicted ccRCC. TLR4 also enhanced the proliferative, migratory and invasive abilities in cultured ccRCC cells. Moreover, TLR4 had close relationships with immune checkpoints and infiltrated immune cells. ccRCC cases with elevated TLR4 expression had prolonged overall survival, suggesting a prognostic value for TLR4. Finally, a pan-cancer analysis demonstrated TLR4 had differential expression in various malignancies in comparison with normal tissue samples. Conclusions: This study revealed prognostic values for ICD-associated genes, particularly TLR4, and experimentally validated the inducing effects of TLR4 on ccRCC progression in vitro. We also demonstrated the associations of TLR4 with immune cell infiltration, providing a novel strategy for prognostic evaluation and a novel therapeutic target in ccRCC.

Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is, by far, the most prevalent and fatal kind of kidney cancer. Ferrochelatase (FECH) is an enzyme that performs a significant function in the onset and progression of many distinct kinds of malignant tumors. Nevertheless, its predictive usefulness in renal clear cell carcinoma (RCC) has not yet been fully investigated.MethodsFECH expression in ccRCC and healthy adjoining tissues was primarily screened utilizing data sourced from The Cancer Genome Atlas (TCGA) and subsequently validated using data from an independent cohort derived from the Gene Expression Omnibus (GEO) and the Human Protein Atlas HPA databases. The relationship among FECH expression, clinicopathological parameters, and overall survival (OS) was assessed utilizing multivariate analysis and Kaplan-Meier survival curves. Additionally, the protein networks with FECH interaction were constructed with the aid of the online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Gene ontology (GO) analysis, and gene set enrichment analysis (GSEA) were conducted based on TCGA data, and a single-sample GSEA was utilized to explore the link between FECH expression and the infiltration status of immune cells in the tumor. The Gene Expression Profiling Interactive Analysis (GEPIA) and TIMER databases were utilized to investigate the relationships of FECH expression with the infiltrating immune cells and the matching gene marker sets.ResultsFECH expression was shown to be substantially lowered in ccRCC tumors as opposed to that observed in normal tissues (p < 0.05). Lower levels of FECH expression were shown to have a strong association with higher grades of cancer and more advanced TNM stages. The findings of multivariate and univariate analyses illustrated that the OS in patients with ccRCC with low FECH expression is shorter in contrast with that in the high FECH expression group (p < 0.05). It was discovered that CPOX and frataxin are key proteins that interact with FECH. ccRCC with FECH deficiency was linked to the lack of infiltrating immune cells and their respective marker sets, which included CD4+ T cells.ConclusionIn ccRCC, decreased FECH expression was linked to disease progression, unfavorable prognosis, and impaired immune cell infiltration.

Project description:BackgroundKidney renal clear cell carcinoma (KIRC) is the most common pathological subtype of renal cell cancer. APOBEC3 activity has been identified in a variety of human cancers. Although its involvement in cancer has been studied widely, its influence on the tumor immune microenvironment remains poorly understood. Therefore, this study aimed to focus on the effect of APOBEC3 on tumor immune microenvironment of KIRC.MethodsIn this study, we comprehensively analyzed the expression and prognostic significance of the APOBEC3 family in pan-cancer using multiple databases. The functions of key APOBEC3 family members were further investigated in KIRC, with APOBEC3G determined to be a candidate biomarker for unfavorable prognosis. We subsequently explored the correlation of APOBEC3G with the tumor immune environment in KIRC by analyzing the Cancer Genome Atlas (TCGA) dataset, then validated the prognostic significance and PD-L1 correlation of APOBEC3G by using tissue microarrays which included 233 primary tumor samples from patients with renal clear cell carcinoma.ResultsThe APOBEC3 family was overexpressed in KIRC and high APOBEC3 expression predicted poor prognosis. In addition, APOBEC3G was positively correlated with the expression of immunoinhibitors such as TIGIT, LAG3, CD96, PD-1, and CTLA4. In addition, APOBEC3G had a positive correlation with immunosuppressive cells, including regulatory T cell and myeloid-derived suppressor cell. Finally, based on 233 clinical samples, we validated that high expression of APOBEC3G contributed to a poor prognosis for KIRC patients and the positive relationship between APOBEC3G and PD-L1 expression. High APOBEC3G expression was also found to be more common in patients with sarcomatoid histology (P = 0.0026).ConclusionsOur study showed that APOBEC3G was a prognostic biomarker correlated with the immune response in KIRC. In addition, APOBE3G had a positive correlation with PD-L1 expression and sarcomatoid histology, perhaps suggesting the potential impact of APOBEC3G on immunotherapy.