Identification of the Pyroptosis-Related Gene Signature for Overall Survival Prediction in Patients With Hepatocellular Carcinoma

Liu, Shuang; Shao, Ruonan; Bu, Xianmin; Xu, Yidan; Shi, Ming

doi:10.3389/fcell.2021.742994

Cited by 14 publications

(19 citation statements)

References 34 publications

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“…Recently, some papers have focused on the prognostic significance of PRGs in HCC. Liu et al built a prognostic model based on CASP1, CHMP6, CASP4, DHX9, GZMA, and DFNA5 expression [ 30 ]. Chen et al screened six genes in the model: BAK1, CHMP4B, DHX9, GSDMC, GSDME, and TREM2 expressions [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma

2022

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Hepatocellular carcinoma (HCC) is one of the most heterogeneous malignancies worldwide with a dismal prognosis. Lack of efficient biomarkers, early detection, and prognosis is still a challenge for HCC. Pyroptosis is a new discovery inflammatory form of programmed cell death. There is growing evidence revealed that pyroptosis plays a role in physiological and pathological conditions of human cancers. However, the prognostic evaluation of these pyroptosis-related genes (PRGs) in HCC remains blank. Consensus clustering of PRGs was used to classify 374 patients with HCC from the TCGA-LIHC cohort. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 2-gene prognostic gene model (PLCG1 and GSDMC) was built and indicated the survival rate in HCC with medium-to-high accuracy. Then, the median risk score from the TCGA cohort was utilized; the prognostic gene model was also accurate in Gene Expression Omnibus (GEO) cohort. The functional enrichment analysis indicated that the oncogenic properties are associated with prominent hallmarks of cancer. The ssGSEA analyses and TIMER database indicated that immune infiltration tumor microenvironment in the HCC. In conclusion, our findings provide a foundation for further research targeting PRGs and their immune microenvironment.

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Section: Discussionmentioning

confidence: 99%

Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma

2022

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“…These findings undoubtedly point toward the fact that pyroptosis profoundly affects the prognosis and immune process in multiple cancers. Although there is also some research reporting that pyroptosis-related (PR) genes have crucial functions in HCC ( Liu, Shao, Bu, Xu, and Shi 2021 ; Zheng et al, 2021 ), its underlying mechanisms remain incompletely understood. In view of this, we constructed a novel PR risk signature through Lasso regression analysis based on an improved PR gene set.…”

Section: Introductionmentioning

confidence: 99%

Pyroptosis-Related Risk Signature Exhibits Distinct Prognostic, Immune, and Therapeutic Landscapes in Hepatocellular Carcinoma

Zhao

Song²,

et al. 2022

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) is a common abdominal cancer. The existing therapeutic approaches often fail to achieve satisfactory results. Pyroptosis, an inflammatory form of programmed cell death, provides new ideas for anticancer treatment. However, the roles of pyroptosis-related (PR) genes (PRGs) in HCC remain elusive.Methods: Differentially expressed genes (DEGs) (n = 22) were screened out using TCGA and GTEx databases. A novel PR risk signature was constructed through Lasso regression analysis. Its prognostic value was evaluated through a series of survival analyses and was tested in ICGC and GSE14520 cohorts. CIBERSORT, ssGSEA, and ESTIMATE methods were employed to determine the effects of the PR risk score on the tumor immune microenvironment (TIM). The TIDE scoring system, IMvigor210 cohort, GSE109211 dataset, and GSDC database were applied to explore the associations of the PR risk score with therapeutic effects. The biofunctions of WNK1 in hepatocellular cancer (HC) cells were confirmed through qPCR, colony formation, and Transwell assays.Results: Overall, 22 of 45 PRGs (48.9%) were abnormally expressed in HCC samples. Then, a PR risk signature consisting of eight PRGs was constructed. A high PR risk score led to an unfavorable prognosis. The PR risk score was identified as an independent prognostic factor of HCC and could increase the decision-making benefit of the traditional TNM model. In addition, we established a nomogram containing the clinical stage and PR risk score to predict the survival rates of HCC patients. The prognostic value of the PR model was successfully validated in ICGC and GSE14520 cohorts. Moreover, high PR risk conferred the decreased infiltration level of CD8+ T cells and weakened the activities of “cytolytic activity” pathways. As for therapeutic correlation, a high PR risk score seemed to imply a poor efficacy of PD-1/L1 inhibitors and sorafenib. Finally, the overexpression of WNK1 could promote the proliferation, migration, and invasion of HC cells.Conclusions: The PR risk score was closely related to the prognosis, antitumor immune process, therapeutic outcomes, and malignant progression of HCC. WNK1, the core regulator of pyroptosis, possesses pro-oncogenic abilities, showing promise as a novel treatment target.

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“…Pyroptosis-induced inflammation has been shown to stimulate antitumour immunity and synergistically with checkpoint inhibitors (24). Previous research has concentrated on developing prognostic signatures or immune microenvironments involving pyroptosis genes (25,26). There have been fewer reports of lncRNAs linked to pyroptosis in HCC.…”

Section: Discussionmentioning

confidence: 99%

Prognosis and Tumour Immune Microenvironment of Patients With Hepatocellular Carcinoma by a Novel Pyroptosis-Related lncRNA Signature

Zhang

Shang

et al. 2022

Front. Immunol.

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Worldwide, hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. However, the survival rate of patients with HCC continues to be poor. The recent literature has revealed that long non-coding RNAs (lncRNAs) and the occurrence of pyroptosis can perform a substantial task in predicting the prognosis of the respective condition along with the response to immunotherapy among HCC patients. Thus, screening and identifying lncRNAs corelated with pyroptosis in HCC patients are critical. In the current study, pyroptosis-related lncRNAs (PR-lncRNAs) have been obtained by co-expression analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) and univariate and multivariate Cox regression assessments have been performed to develop a PR-lncRNA prognostic model. The risk model was analysed using Kaplan–Meier analysis, principal component analysis (PCA), functional enrichment annotation, and a nomogram. The risk model composed of five PR-lncRNAs was identified as an independent prognostic factor. The tumour immune microenvironment (TIME) was assessed using model groupings. Finally, we validated the five PR-lncRNAs in vitro using a quantitative real-time polymerase chain reaction (qRT-PCR).

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Identification of the Pyroptosis-Related Gene Signature for Overall Survival Prediction in Patients With Hepatocellular Carcinoma

Cited by 14 publications

References 34 publications

Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma

Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma

Pyroptosis-Related Risk Signature Exhibits Distinct Prognostic, Immune, and Therapeutic Landscapes in Hepatocellular Carcinoma

Prognosis and Tumour Immune Microenvironment of Patients With Hepatocellular Carcinoma by a Novel Pyroptosis-Related lncRNA Signature

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