TACC3 is a prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune cell infiltration and T cell exhaustion.
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ABSTRACT:
SUBMITTER: Fan X
PROVIDER: S-EPMC8034911 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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: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: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: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:Purpose: The interplay of inflammation and immunity affects all stages from tumorigenesis to progression, and even tumor response to therapy. A growing interest has been attracted from the biological function of MICALL2 to its effects on tumor progression. This study was designed to verify whether MICALL2 could be a prognostic biomarker to predict kidney renal clear cell carcinoma (KIRC) progression, inflammation, and immune infiltration within tumor microenvironment (TME). Methods: We firstly analyzed MICALL2 expressions across 33 cancer types from the UCSC Xena database and verified its expression in KIRC through GEPIA platform and GEO datasets. The clinicopathological characteristics were further analyzed based on the median expression. Kaplan-Meier method, univariate and multivariate analyses were applied to compare survival outcomes. ESTIMATE and CIBERSORT algorithms were performed to assess immune infiltration, and a co-expression analysis was conducted to evaluate the correlation between MICALL2 and immunoregulatory genes. Enrichment analysis was finally performed to explore the biological significance of MICALL2. Results: MICALL2 was highly expressed in 16 types of cancers compared with normal tissues. MICALL2 expression increased with advanced clinicopathological parameters and was an independent predictor for poor prognosis in KIRC. Moreover, MICALL2 closely correlated with inflammation-promoting signatures and immune infiltration including T cell exhaustion markers. Consistently, MICALL2 involved in the regulation of signaling pathways associated with tumor immunity, tumor progression, and impaired metabolic activities. Conclusion: MICALL2 can function as a prognostic biomarker mediating inflammation, immune infiltration, and T cell exhaustion within the microenvironment of KIRC.
| S-EPMC8899381 | biostudies-literature
Project description:ObjectiveThe objective of the study was to investigate the expression of LAMTOR3 in kidney renal clear cell carcinoma (KIRC) and its clinical significance.MethodsThe expression of LAMTOR3 in KIRC and its relationship with clinical features were analyzed using the UALCAN online database. The results were verified using KIRC gene chip data and clinical specimens. The prognosis of KIRC patients was analyzed with the GEPIA2 database. GO, KEGG, and GSEA analyses were conducted to analyze the possible molecular mechanism of LAMTOR3 in KIRC. Immunohistochemical (IHC) and hematoxylin and eosin (H&E) staining were used for histopathological detection.ResultsUALCAN database analysis showed that LAMTOR3 expression in KIRC was significantly lower than in normal kidney tissues and correlated with the clinical stage, pathological grade, and tumor genotype (p < .05). GSE53757 dataset analysis consistently showed that the expression of LAMTOR3 in KIRC was significantly lower than in normal kidney tissues (p < .01). GEPIA2 database analysis indicated that patients with low LAMTOR3 expression had poor overall and disease-free survival rates. GSEA analysis suggested that LAMTOR3 positively regulated the citrate cycle and drug metabolism cytochrome P450 and negatively regulated folate biosynthesis and olfactory transduction. The expression of LAMTOR3 in KIRC was also significantly correlated with immune cell infiltration. Finally, IHC showed that LAMTOR3 expression in the KIRC tissues was lower than in the adjacent normal tissues.ConclusionLAMTOR3 expression is significantly lower in KIRC. LAMTOR3 may be a potential marker for KIRC diagnosis and therapy.
| S-EPMC9459259 | 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
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: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.
| S-EPMC9768312 | biostudies-literature