Upregulated GSDMB in Clear Cell Renal Cell Carcinoma Is Associated with Immune Infiltrates and Poor Prognosis

Cui, Yuanshan; Chai, Yumeng; Zhang, Yong

doi:10.1155/2021/7753553

Cited by 21 publications

(21 citation statements)

References 33 publications

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“…GSDMB is located in a genomic region that is frequently amplified during cancer development. Therefore, GSDMB function may affect tumor progression and metastasis [ 44 , 45 ]. In our study, GSDMB was downregulated in BC tissues, as shown by the bioinformatics, qPCR, and Western blotting results.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer

Chen

et al. 2022

Cancers

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RBPs in the development and progression of bladder cancer (BC) remains unclear. Here, we elucidated the role of RBPs in predicting the survival of patients with BC. Clinical information and RNA sequencing data of the training and validation cohorts were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases, respectively. Survival-related differentially expressed RBPs were identified using Cox regression analyses. A total of 113 upregulated and 54 downregulated RBPs were observed, with six showing prognostic values (AHNAK, MAP1B, LAMA2, P4HB, FASN, and GSDMB). In both the GSE32548 and GSE31684 datasets, patients with low-risk scores showed longer overall survival than those with high-risk scores. AHNAK, MAP1B, P4HB, and FASN expression were significantly upregulated in both BC tissues and cell lines. BC tissues from the high-risk group showed higher proportions of naïve CD4+ T cells, macrophages M0 and M2, and neutrophils and lower proportions of plasma cells, CD8+ T cells, and T-cell follicular helper compared to the low-risk group. AHNAK knockdown significantly inhibited the proliferation, invasion, and migration of BC cells in vitro and inhibited the formation and growth of subcutaneous tumors in vivo. We thus developed and functionally validated a novel six-RBP-based prognostic model for BC.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer

Chen

et al. 2022

Cancers

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“…For example, the tumor-suppressive effect of GSDME is mediated by tumor-infiltrating natural killer (NK) and CD8+T lymphocytes ( Zhang et al, 2020 ). Meanwhile, the overexpression of GSDMB in cancer cells leads to the recruitment of immune cells and promotes tumor mobility and invasion ( Hergueta-Redondo et al, 2014 ; Cui et al, 2021 ). We have observed that the expression of GSDM genes is amplified in many human cancers, particularly kidney cancer.…”

Section: Discussionmentioning

confidence: 99%

A systematic pan-cancer analysis of the gasdermin (GSDM) family of genes and their correlation with prognosis, the tumor microenvironment, and drug sensitivity

et al. 2022

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Background: Pyroptosis is a programmed cell death process mediated by the gasdermin (GSDM) protein. However, limited research has been conducted to comprehensively analyze the contribution of the GSDM family in a pan-cancer setting.Methods: We systematically evaluated the gene expression, genetic variations, and prognostic values of the GSDM family members. Furthermore, we investigated the association between the expression of GSDM genes and immune subtypes, the tumor microenvironment (TME), the stemness index, and cancer drug sensitivities by means of a pan-cancer analysis.Results: GSDM genes were highly upregulated in most of the tested cancers. Low-level mutation frequencies within GSDM genes were common across the examined types of cancer, and their expression levels were associated with prognosis, clinical characteristics, TME features, and stemness scores in several cancer types, particularly those of the urinary system. Importantly, we found that the expressions of GSDMB, GSDMC, and GSDMD were higher in kidney carcinomas, and specifically kidney renal clear cell carcinoma (KIRC); which adversely impacted the patient outcome. We showed that GSDMD was potentially the most useful biomarker for KIRC. The drug sensitivity analysis demonstrated that the expressions of GSDM genes were correlated with the sensitivity of tumor cells to treatment with chemotherapy drugs nelarabine, fluphenazine, dexrazoxane, bortezomib, midostaurin, and vincristine.Conclusion: GSDM genes were associated with tumor behaviors and may participate in carcinogenesis. The results of this study may therefore provide new directions for further investigating the role of GSDM genes as therapeutic targets in a pan-cancer setting.

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“…Further, dead patients had decreased PANK1 levels compared to alive patients according to the OS, DSS, and progression-free interval (PFI) outcomes (see Figure2H-2J). Univariate Cox analysis indicated that key clinical characteristics exhibited a significant correlation with clinical prognosis according to previous study(30). Patients with low PANK1 expression increased mortality compared with high…”

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confidence: 61%

PANK1 associates with cancer metabolism and immune infiltration in clear cell renal cell carcinoma: a retrospective prognostic study based on the TCGA database

Wang¹,

Liu²,

Luo³

et al. 2022

Transl Cancer Res TCR

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Background: Identify key biomarkers to improve the clinical prognosis of patients with advanced and metastatic clear cell renal cell carcinoma (ccRCC) remains an important research topic. Recently, ccRCC has been regarded as a metabolic disease. Pantothenate kinase-1 (PANK1) has been shown to play an important regulatory role in global metabolism and associates with the pathogenesis of hepatocellular carcinoma. Therefore, we aimed to investigate the role of PANK1 in the prognosis of ccRCC and in metabolism and immunity. Methods: PANK1 messenger ribonucleic acid (RNA) expression patterns in ccRCC using The Cancer Genome Atlas (TCGA) database. The clinical prognostic significance of PANK1 in ccRCC and a Cox regression was performed to evaluate the clinical factors associated with prognosis with confounding factors adjusted. The signaling pathways related to PANK1 expression were identified by Gene Ontology (GO) investigation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The Tumor Immune Estimation Resource database was used to analyze the correlation between PANK1 and tumor-infiltrating immune cells.Results: A total of 539 ccRCC patients and corresponding clinical samples and data from TCGA were included in this analysis. Significant differences were observed in PANK1 expression levels between tumor tissues and adjacent normal tissues in both TCGA-Kidney Renal Clear Cell Carcinoma cohort (4.40 vs.2.94, P<0.001). PANK1 expression was found to be correlated with pathological stage, histological grade, age, sex, and clinical prognosis. Specifically, the low expression of PANK1 was found to be closely related to poor overall survival (OS), disease-specific survival (DSS), and the progression-free survival (PFS) in ccRCC patients. The receiver operating characteristic curve suggested that PANK1 could be a potential prognostic biomarker (area under the curve =0.880), and that the promoter methylation levels of PANK1 were correlated with clinical factors. Further, PANK1 expression was found to be associated with multiple immune cell types and correlated with the enrichment of these cells. Finally, we further investigated the role of PANK1 in tumor growth and mitochondrial metabolism using ccRCC cells.Conclusions: PANK1 correlates with ccRCC prognosis, tumor immune status and metabolism using the TGCA data. PANK1 might be a prognostic marker of clinical prognosis for ccRCC patients. the following article in accordance with the TRIPOD reporting checklist (available at https://tcr.amegroups.com/ article/view/10.21037/tcr-22-1488/rc). Methods Study design and research proceduresThis study is a retrospective prognostic study analyzing the expression difference of PANK1 between tumor and adjacent normal tissues, correlations with the clinical factors, overall

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Upregulated GSDMB in Clear Cell Renal Cell Carcinoma Is Associated with Immune Infiltrates and Poor Prognosis

Cited by 21 publications

References 33 publications

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer

Integrated Analysis and Identification of Critical RNA-Binding Proteins in Bladder Cancer

A systematic pan-cancer analysis of the gasdermin (GSDM) family of genes and their correlation with prognosis, the tumor microenvironment, and drug sensitivity

PANK1 associates with cancer metabolism and immune infiltration in clear cell renal cell carcinoma: a retrospective prognostic study based on the TCGA database

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