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TACC3 is a prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune cell infiltration and T cell exhaustion.

ABSTRACT: Growing evidence has demonstrated that transforming acidic coiled-coil protein 3 (TACC3), a member of the TACC family, may be involved in regulating cell mitosis, transcription, and tumorigenesis. However, the role of TACC3 in kidney renal clear cell carcinoma (KIRC) remains unknown. In this study, multiple databases were used to determine the pattern of TACC3 in KIRC. We found that high TACC3 expression was associated with poor overall survival (OS) in stage I, II, IV and grade 3 KIRC patients. Univariate and multivariate Cox regression analyses showed that TACC3 was an independent risk factor for OS among KIRC patients. Moreover, TACC3 expression correlated with immune cell infiltration levels of B cells, T cells (CD8+, CD4+, follicular helper, regulatory and gamma delta), total and resting natural killer cells, total and activated dendritic cells, and resting mast cells. Furthermore, T cell exhaustion markers, such as PD1, CTLA4, LAG3 and TIM-3 were highly expressed in TACC3 overexpressing tissues. In addition, GSEA analysis revealed that the role of TACC3 in KIRC may be closely linked to immune-associated pathways. Therefore, our study reveals that TACC3 is a prognostic biomarker for OS among KIRC patients and may be associated with immune cell infiltration and T cell exhaustion.

SUBMITTER: Fan X

PROVIDER: S-EPMC8034911 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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TACC3 is a prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune cell infiltration and T cell exhaustion.

Fan Xiaoyan X Liu Boyi B Wang Zhiyu Z He Dongwei D

Aging 20210310 6

Growing evidence has demonstrated that transforming acidic coiled-coil protein 3 (TACC3), a member of the TACC family, may be involved in regulating cell mitosis, transcription, and tumorigenesis. However, the role of TACC3 in kidney renal clear cell carcinoma (KIRC) remains unknown. In this study, multiple databases were used to determine the pattern of TACC3 in KIRC. We found that high TACC3 expression was associated with poor overall survival (OS) in stage I, II, IV and grade 3 KIRC patients. ...[more]

PMID: 33714201

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Project description:Background: Actin-related protein 2/3 complex subunit 1B (ARPC1B) is reported to be involved in tumorigenesis and progression. However, its role in kidney renal clear cell carcinoma (KIRC), correlation with tumor-infiltrating immune cells, and prognostic significance remain unclear. Methods: Data sets from the TCGA, GTEx, GEPIA, GEO, UALCAN, and CPTAC databases were extracted and analyzed to investigate the expression difference, prognosis, and clinicopathological features of ARPC1B. Single-sample Gene Set Enrichment Analysis (ssGSEA), CIBERSORT, and TISCH2 analysis were used to examine the relationship between ARPC1B expression and tumor immune infiltration in KIRC. The potential function of ARPC1B in KIRC was explored by GO functional annotation and KEGG pathway analysis. The TIDE algorithm was used to predict and analyze the relationship between ARPC1B expression and response to immune checkpoint blockade (ICB). The expression of ARPC1B was further validated by using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Results: The study showed that ARPC1B expression was an independent prognostic factor of KIRC, with high ARPC1B expression being associated with poor overall survival (OS). Enrichment of GO annotation and pathway analysis showed multiple immune-related functional pathways affected by ARPC1B such as regulation of immune effector process, inflammatory response regulation, antigen processing and presentation, asthma, autoimmune thyroid disease, graft versus host disease, intestinal immune network for IgA production, and type I diabetic mellitus. Moreover, ARPC1B expression positively correlated with infiltrating levels of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in KIRC. Importantly, high ARPC1B expression predicted a low response to ICB in KIRC. Conclusion: This study indicates that ARPC1B expression is an independent prognostic biomarker for OS in KIRC patients. High ARPC1B expression is closely associated with MDSCs and Tregs infiltration. These findings suggest that ARPC1B may serve as a biomarker for prognosis and immune infiltration in KIRC, potentially aiding in the development of novel treatment strategies to improve the survival outcomes for KIRC patients.

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.

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.

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TACC3 is a prognostic biomarker for kidney renal clear cell carcinoma and correlates with immune cell infiltration and T cell exhaustion.

Publications

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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