YTHDF2 is a Potential Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma
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ABSTRACT:
SUBMITTER: Su G
PROVIDER: S-EPMC8429956 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThis study aims to explore the prognostic significance of Proline-rich γ-carboxyglutamic acid protein 2 (PRRG2) in Kidney Renal Clear Cell Carcinoma (KIRC), a prevalent and deadly cancer, and its association with immune cell infiltration, a key strategy in developing effective biomarkers.MethodsThe study meticulously elucidated the prognostic significance and potential role of PRRG2 in KIRC, correlating its expression with patient sex, age, metastasis, and pathological stage. Utilizing Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the involvement of PRRG2 in immune response was investigated. The association between PRRG2 expression and immune cell infiltration was also scrutinized. Ultimately, cellular and tissue identity were confirmed via immunohistochemical staining and quantitative real-time PCR.ResultsThe study elucidates a notable decrease in PRRG2 expression in KIRC patients, correlating with demographic factors, metastasis, and pathological staging, and portending an unfavorable prognosis. Bioinformatic analyses underscore PRRG2's role in immune response, with its expression significantly tied to immune cell infiltration and marker expression.ConclusionPRRG2 may potentially impact prognosis in KIRC patients by regulating immune infiltration, thus rendering PRRG2 a promising candidate prognostic biomarker for KIRC-associated immune infiltration.
| S-EPMC10792142 | biostudies-literature
Project description:BackgroundGRAM structural domain-containing protein 1A (GRAMD1A) is upregulated in a variety of human cancer tissues and is closely associated with tumourigenesis and progression.MethodsPatient RNA-sequencing data and clinicopathological information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The expression of GRAMD1A in kidney cancer cell lines and KIRC patients was analysed by quantitative polymerase chain reaction (qPCR). Receiver Operator Characteristic (ROC) curves, nomograms, Kaplan-Meier analysis, forest plots, and COX analysis were used to assess the diagnostic and prognostic value of GRAMD1A in KIRC, and gene set enrichment analysis (GSEA) was used to explore its potential signalling pathways. In addition, the Sangerbox website, Kaplan-Meier plotter database, and TISIDB and TIMER databases were used to further analyse the correlation of GRAMD1A with microsatellite instability (MSI), tumour mutational burden (TMB), immune checkpoint genes, and tumour-infiltrating lymphocytes (TILs).ResultsGRAMD1A was significantly highly expressed in KIRC and associated with shorter overall survival and relapse-free survival (P < 0.05). The AUC value of the ROC curve to identify KIRC and normal renal tissues was 0.942. Forest plot and COX analysis visualized that GRAMD1A could be an independent prognostic factor in KIRC patients (P < 0.01), and nomograms to determine the overall survival (OS) of KIRC patients also showed good efficacy (C-index: 0.776). Moreover, Spearman correlation analysis showed a positive correlation between GRAMD1A and MSI, TMB (P < 0.01). On the other hand, GRAMD1A was also found to be closely associated with immune checkpoint genes. Meanwhile, patients with KIRC with high GRAMD1A expression had a relatively low hazard ratio (HR) of death when B lymphocytes, natural killer T cells, CD4+ T lymphocytes, CD8+ T lymphocytes, and macrophages were enriched in the tumour microenvironment (TME), and a greater HR of death when regulatory T lymphocytes with tumour-specific immunosuppressive effects were significantly enriched. Last, GSEA shows that GRAMD1A is closely associated with the regulation of energy metabolism in KIRC.ConclusionsGRAMD1A is a promising diagnostic and prognostic biomarker for patients with KIRC, and its biological function correlates to some extent with immune infiltration in TME.
| S-EPMC9293538 | biostudies-literature
Project description:The TBC1D3 family is overexpressed in many cancers, including kidney renal clear cell carcinoma (KIRC), which is associated with tumor-infiltrating lymphocytes. However, the expression and prognosis of TBC1D3 family and tumor-infiltrating lymphocytes in KIRC remain unknown. In the present study, we systematically explored and validated the expression and prognostic value of TBC1D3 family expression in KIRC using multiple public databases. In addition, the function of the TBC1D3 family members and the correlations between TBC1D3 family expression and KIRC immune infiltration levels were investigated. We found that TBC1D3 family members were rarely mutated (less than 5 frequencies). TBC1D3 family was overexpressed in KIRC; high expression of the TBC1D3 family members was correlated with poor prognosis. In addition, TBC1D3D may positively regulate proliferation, and overexpression of TBC1D3 promoted clear cell renal cell carcinoma proliferation in vitro. In terms of immune infiltrating levels, TBC1D3 family expression was positively associated with CD4+ T cells infiltrating levels. These findings suggest that the TBC1D3 family expression is correlated with prognosis and immune infiltrating levels. Therefore, the TBC1D3 family can be used as a biomarker for KIRC and a prognostic biomarker for determining the prognosis and immune infiltration levels in KIRC.
| S-EPMC8433061 | biostudies-literature
Project description:BackgroundSIRT7 has been shown to be expressed in many cancer types, including clear cell renal 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.MethodsRelationships 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 clear cell renal cell carcinoma patients. The functional role of SIRT7 in this cancer type was assessed through GO/KEGG enrichment analyses and immune cell infiltration analyses.ResultsIn 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.ConclusionIncreased 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.
| S-EPMC8942347 | biostudies-literature
Project description:BackgroundAbnormal spindle microtubule assembly (ASPM) is a centrosomal protein and that is related to a poor clinical prognosis and recurrence. However, the relationship between ASPM expression, tumor immunity, and the prognosis of different cancers remains unclear.MethodsASPM expression and its influence on tumor prognosis were analyzed using the Tumor Immune Estimation Resource (TIMER), UALCAN, OncoLnc, and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The relationship between ASPM expression and tumor immunity was analyzed using the TIMER and GEPIA databases, and the results were further verified using qPCR, western blot, and multiplex quantitative immuno fluorescence.ResultsThe results showed that ASPM expression was significantly higher in most cancer tissues than in corresponding normal tissues, including kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), and breast invasive carcinoma (BRCA). ASPM expression was significantly higher in late-stage cancers than in early-stages cancers (e.g., KIRC, KIRP, LIHC, LUAD, and BRCA; p < 0.05), demonstrating a possible role of ASPM in cancer progression and invasion. Moreover, our data showed that high ASPM expression was associated with poor overall survival, and disease-specific survival in KIRC and LIHC (p < 0.05). Besides, Cox hazard regression analysis results showed that ASPM may be an independent prognostic factor for KIRC and LIHC. ASPM expression showed a strong correlation with tumor-infiltrating B cells, CD8+ T cells, and M2 macrophages in KIRC and LIHC.ConclusionsThese findings demonstrate that the high expression of ASPM indicates poor prognosis as well as increased levels of immune cell infiltration in KIRC and LIHC. ASPM expression may serve as a novel prognostic biomarker for both the clinical outcome and immune cell infiltration in KIRC and LIHC.
| S-EPMC9065448 | biostudies-literature
Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is a widespread urogenital neoplasm. However, the therapeutic efficacy of these methods is unsatisfactory. In-depth screening of biomarkers could aid early diagnosis and therapy and predict patient prognosis.MethodsThe GEO datasets were selected with specific criteria. Differentially expressed gene (DEG), weighted gene coexpression network analysis (WGCNA), protein-protein interaction, LASSO, random forest, and Cox regression analyses were applied to identify the independent prognostic biomarkers. Survival analysis, correlation with clinical features, gene set enrichment analysis (GSEA), GO enrichment, immune infiltration analysis, and correlation with cuproptosis-related genes were carried out to determine the prognostic value and possible molecular mechanisms of the TSVR. Wound healing assays, transwell assays, cell colony formation experiments, flow cytometry, and immunohistochemistry (IHC) analysis were used to validate the functional attributes of CRYL1.ResultsFour GEO datasets were included to screen for hub genes. DEG combined with WGCNA showed a key module with 300 genes having the strongest correlation with "survival state" (R2 = -0.24 and P = 7e-8); six genes were identified by LASSO, random forest, and Cytoscape. Finally, CRYL1 (hazard ratio (HR) = 2.01, P < 0.001) was selected as an independent prognostic biomarker. The higher CRYL1 expression group had better DFS and overall survival (OS). GSEA demonstrated that the CRYL1-related DEGs were enriched mainly in the metabolism of sugar, fat, and amino acids. CRYL1 is positively correlated with FDX1 and the LIAS pathway, which are important molecule involved in cuproptosis. CRYL1 affects the infiltration abundance of four immune cells and can predict a positive OS. Wound healing, transwell, cell colony formation, and flow cytometry assays demonstrated that CRYL1 silencing enhances migration and proliferation and leads to a decreased apoptotic ratio. IHC analysis suggested that CRYL1 was highly expressed in adjacent tissues.ConclusionsCRYL1 is a robust predictive marker for clinicopathological characteristics and survival status in ccRCC patients.
| S-EPMC10946081 | biostudies-literature
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.
| S-EPMC9932331 | biostudies-literature
Project description:Background: Kidney renal clear cell carcinoma (KIRC) is not sensitive to radiotherapy and chemotherapy, and only some KIRC patients can benefit from immunotherapy and targeted therapy. Cuproptosis is a new mechanism of cell death, which is closely related to tumor progression, prognosis and immunity. The identification of prognostic markers related to cuproptosis in KIRC may provide targets for treatment and improve the prognosis of KIRC patients. Methods: Ten cuproptosis-related genes were analyzed for differential expression in KIRC-TCGA and a prognostic model was constructed. Nomogram diagnostic model was used to screen independent prognostic molecules. The screened molecules were verified in multiple datasets (GSE36895 and GSE53757), and in KIRC tumor tissues by RT-PCR and immunohistochemistry (IHC). Clinical correlation of cuproptosis-related independent prognostic molecules was analyzed. According to the molecular expression, the two groups were divided into high and low expression groups, and the differences of immune checkpoint and tumor infiltrating lymphocytes (TILs) between the two groups were compared by EPIC algorithm. The potential Immune checkpoint blocking (ICB) response of high and low expression groups was predicted by the “TIDE” algorithm. Results: FDX1 and DLAT were protective factors, while CDKN2A was a risk factor. FDX1 was an independent prognostic molecule by Nomogram, and low expressed in tumor tissues compared with adjacent tissues (p < 0.05). FDX1 was positively correlated with CD274, HAVCR2, PDCD1LG2, and negatively correlated with CTLA4, LAG3, and PDCD1. The TIDE score of low-FDX1 group was higher than that of high-FDX1 group. The abundance of CD4+ T cells, CD8+ T cells and Endothelial cells in FDX1-low group was lower than that in FDX1-high group (p < 0.05). Conclusion: FDX1, as a key cuproptosis-related gene, was also an independent prognostic molecule of KIRC. FDX1 might become an interesting biomarker and potential therapeutic target for KIRC.
| S-EPMC9900009 | biostudies-literature
Project description: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.
| S-EPMC8769242 | biostudies-literature
Project description:The role and underlying mechanism of cytoplasmic polyadenylation element binding protein 3 (CPEB3) in clear cell renal cell carcinoma [ccRCC progression remain poorly characterized. The present study was designed to evaluate the role of CPEB3 in ccRCC and its clinical associations. The overall response rate of first-line therapies (ICIs combined with VEGFR-TKIs or ICI combination) for ccRCC] is 42.0-59.3%, so a number of patients with ccRCC do not benefit from these therapies. To avoid immunosurveillance and immune killing, tumor cells decrease immunogenicity and recruit immunosuppressive cells such as regulatory T cells (Tregs). Tregs inhibit the development of anti-tumor immunity, thereby hindering immune surveillance of cancer and preventing effective anti-tumor immune response in tumor-bearing hosts. The present study analyzed clinical specimens from patients ccRCC and then examined the role of CPEB3 in ccRCC via bioinformatics analysis. CPEB3 expression was significantly reduced in ccRCC compared with normal tissue and low CPEB3 expression was associated with poor overall survival. Moreover, CPEB3 expression was an independent predictor of survival. CPEB3 expression was positively associated with immune biomarkers [CD274, programmed cell death 1 ligand 2, Hepatitis a virus cellular receptor 2, Chemokine (C-X-C motif) ligand (CXCL)9, CXCL10, Inducible T cell costimulatory, CD40, CD80 and CD38] that improve the outcome of anti-tumor immune responses. CPEB3 expression in ccRCC also affected the status of 24 types of infiltrating immune cell, of which Tregs were the most significantly negatively correlated cell type. CPEB3 may serve as a prognostic biomarker in ccRCC and its mechanism may be related to the regulation of Tregs.
| S-EPMC10928475 | biostudies-literature