Integrated analysis of expression, prognostic value and immune infiltration of GSDMs in hepatocellular carcinoma

Hu, Kuan; Xu, Zhijie; Yao, Lei; Yan, Yuanliang; Zhou, Lei; Li, Juanni

doi:10.18632/aging.203669

Cited by 21 publications

(23 citation statements)

References 49 publications

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“…Recently, it has been reported that two members of the GSDM family, namely GSDMD and GSDME , stimulate numerous downstream pyroptotic pathways, and the downregulation of these molecules conversely contributed to tumorigenesis and proliferation in the tumor cell microenvironment ( Wang et al, 2018a ; Gao et al, 2018 ; De Schutter et al, 2021 ). Although previous studies have investigated the gene expression patterns of some pyroptosis genes in tumors and normal tissues ( Hu et al, 2021 ; Qiu et al, 2021 ), their analyses were restricted to a specific cancer type. Therefore, the objectives of the present analysis were to determine the expression patterns of GSDM genes in numerous cancer types and adjacent normal tissues, as well as evaluate their association with immune infiltration, genetic variation, and drug sensitivity.…”

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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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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“…Pyroptosis is involved in the progression of multiple types of tumors, including HCCs. Hu et al Hu et al (2021) showed that six gasdermin (GSDM) family members involved in pyroptosis play an indispensable role in HCC. Higher GSDME expression is positively correlated with shorter overall survival (OS) and disease-specific survival (DSS) in HCC patients.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of the Correlation Between Pyroptosis-Related LncRNAs and Tumor Microenvironment, Prognosis, and Immune Infiltration in Hepatocellular Carcinoma

Wang

et al. 2022

Front. Genet.

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Background: Accumulating evidence shows that pyroptosis plays a crucial role in hepatocellular carcinoma (HCC). However, the relationship between pyroptosis-related long non-coding RNAs (lncRNAs) and HCC tumor characteristics remains enigmatic. We aimed to explore the predictive effect of pyroptosis-related lncRNAs (PRLs) in the prognosis of HCC.Methods: We comprehensively analyzed the role of the PRLs in the tumor microenvironment and HCC prognosis by integrating genomic data from patients of HCC. Consensus clustering analysis of PRLs was applied to identify HCC subtypes. A prognostic model was then established with a training cohort from The Cancer Genome Atlas (TCGA) using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Further, we evaluated the accuracy of this predictive model using a validation set. We predicted IC50s of commonly used chemotherapeutic and targeted drugs through the R package pRRophetic.Results: Based on pyroptosis-related lncRNAs, a prognostic risk signature composed of seven PRLs (MKLN1AS, AL031985.3, SNHG4, GHRLOS, AC005479.2, AC099850.4, and AC026412.3) was established. For long-term prognosis of HCC patients, our model shows excellent accuracy to forecast overall survival of HCC individuals both in training set and testing set. We found a significant correlation between clinical features and the risk score. Patients in the high-risk group had tumor characteristics associated with progression such as aggressive pathological grade and stage. Besides that, gene set enrichment analysis (GSEA) showed that cell cycle and focal adhesion were significantly enriched in the high-risk group.Conclusion: The association of the risk model constituted by these seven pyroptosis-related lncRNAs with clinical prognosis, tumor microenvironment, chemotherapy and small molecule drugs was evaluated. Our study provides strong evidence for individualized prediction of prognosis, shedding light on immunotherapy in HCC patients.

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“…Our results indicated the higher mRNA expression of GSDMC and GSDME is the indicator for the poor prognosis of HCC. The recent study also showed that the dysregulation of the gasdermin family might be related to the survival prognosis and immune infiltration of HCC [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

A Pyroptosis-Based Prognostic Model for Immune Microenvironment Estimation of Hepatocellular Carcinoma

et al. 2022

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Background. Hepatocellular carcinoma (HCC), an aggressive malignant tumor, has a high incidence and unfavorable prognosis. Recently, the synergistic effect of pyroptosis in antitumor therapy and regulation of tumor immune microenvironment has made it possible to become a novel therapeutic method, but its potential mechanism still needs further exploration. Methods. Differentially expressed genes with prognostic value in Liver Hepatocellular Carcinoma Project of The Cancer Genome Atlas (TCGA-LIHC) cohort were screened and incorporated into the risk signature by Cox proportional hazards regression model and least absolute shrinkage and selection operator. Kaplan-Meier (KM) curves and receiver operating characteristic (ROC) curves were applied to conduct survival comparisons and estimate prediction ability. The dataset of Liver Cancer-RIKEN, Japan Project from International Cancer Genome Consortium (ICGC-LIRI-JP) cohort was used to verify the reliability of the signature. Correlation analysis between clinicopathological characteristics, immune infiltration, drug sensitivities, and risk scores was conducted. Functional annotation analyses were performed for the genes differentially expressed between high-risk and low-risk groups. Results. A risk signature consisting of 6 pyroptosis-related genes in HCC was developed and validated. KM curves and ROC curves revealed its considerable predictive accuracy. Higher risk scores meant more advanced grade, higher alpha-fetoprotein level, and stronger invasive ability. Overexpressed genes in high-risk population were more enriched in the immune-associated pathways, and these patients might be more sensitive to immune checkpoint inhibitors instead of Sorafenib. Intriguingly, 6 identified genes were promising to be prognostic biomarkers and therapeutic targets of HCC. Conclusions. The signature may have crucial clinical significance in predicting survival prognosis, immune infiltration, and drug efficacy based on pyroptosis-related genes.

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Integrated analysis of expression, prognostic value and immune infiltration of GSDMs in hepatocellular carcinoma

Cited by 21 publications

References 49 publications

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

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

Comprehensive Analysis of the Correlation Between Pyroptosis-Related LncRNAs and Tumor Microenvironment, Prognosis, and Immune Infiltration in Hepatocellular Carcinoma

A Pyroptosis-Based Prognostic Model for Immune Microenvironment Estimation of Hepatocellular Carcinoma

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