A Pyroptosis-Related Gene Signature to Predict Patients’ Prognosis and Immune Landscape in Liver Hepatocellular Carcinoma

Wang, Jiakun; Huang, Zhihao; Lü, Hongmei; Zhang, Rongguiyi; Feng, Qian; He, Aoxiao

doi:10.1155/2022/1258480

Cited by 9 publications

(8 citation statements)

References 40 publications

(40 reference statements)

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“…Besides, we constructed a novel multigene predictive model for HCC patients and validated the model genes' expression differences through several different analyses. Recently, some similar studies about different PRG research in HCC subtype identification [40][41][42][43][44][45][46] and predictive model construction [40][41][42][43][44][45][46][47][48][49] have been published. However, in all the previous subtype identification studies, the cluster analyses were conducted only in one cohort while we also tested in a validation cohort.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

Lai

Liu

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Hepatocellular carcinoma (HCC) is a worldwide malignant cancer with high incidence and mortality. Considering the high heterogeneity of HCC, clarifying molecular characteristics associated with HCC development could help improve patients’ outcomes. Pyroptosis is a novel form of cell death and is noted to be implicated in HCC pathogenesis whereas its molecular feature in HCC is unclear. Thus, we intended to clarify the molecular characteristic as well as the clinical significance of pyroptosis for HCC. A systematic bioinformatics analysis was conducted among 40 pyroptosis-related genes based on The Cancer Genome Atlas, the International Cancer Genome Consortium, and the Gene Expression Omnibus databases. A total of 12 HCC-associated pyroptosis-related genes (HPRGs) were identified to be overexpressed in HCC tissues and significantly connected to patients’ poor survival. Through consensus clustering based on the HPRGs’ expression, we found patients could be stratified into two distinctive pyroptosis subtypes, PyLow and PyHigh. The PyHigh group owned a notable lower survival rate and a higher high-grade proportion compared with the PyLow subtype. Besides, patients’ sensitivities to chemotherapeutic drugs also presented distinctive differences between the two subtypes. Indicated by pathway enrichment analysis and immune characteristic difference analysis, the distinctions between the pyroptosis subtypes may be related to tumor immunity. Further, a five-gene risk model composed of BAK1, CHMP4A, CHMP4B, DHX9, and GSDME was established. Subsequent analyses demonstrated that the model could credibly classify patients as low or high risk and was an independent prognostic indicator for HCC. Abnormal expressions of the five genes were validated by biological experiments and new bioinformatics analysis. In conclusion, this study recognized and verified two heterogeneous pyroptosis subtypes and a predictable prognosis model for HCC. Our work may help facilitate the clinical management and treatment of HCC and understand the functions of pyroptosis in oncology.

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Section: Discussionmentioning

confidence: 99%

Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

Lai

Liu

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Some related studies have been on pyroptosis-related gene signatures in HCC, which proved that PRGs played important roles in predicting the prognosis of HCC [ 6 – 8 ]. Unlike these studies, we firstly added mutation data analysis of PRGs, and the ICGC-LIRI-JP dataset to verify the validity of the model.…”

Section: Discussionmentioning

confidence: 99%

“…The results of qRT-PCR suggested that BAK1, BAX, CHMP2A, GSDME, IL1A, TP53, TP63, GPX4, PRKACA and SCAF11 were highly expressed in HCC tissues. Some related studies have been on pyroptosis-related gene signatures in HCC, which proved that PRGs played important roles in predicting the prognosis of HCC [6][7][8]. Unlike these studies, we firstly added mutation data analysis of PRGs, and the ICGC-LIRI-JP dataset to verify the validity of the model.…”

Section: Discussionmentioning

confidence: 99%

“…Pyroptosis, designated as a novel programmed cell death pathway usually caused by activation of inflammasome and caspase, plays an important role in the progress of HCC [4][5][6][7][8]. Pyroptosis pathways include canonical pyroptotic pathways mediated by caspase-1 dependence and non-canonical pyroptotic pathways mediated by caspase-4, − 5, and − 11.…”

Section: Introductionmentioning

confidence: 99%

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Pyroptosis related genes signature predicts prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma

et al. 2022

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Little is known on the relationship between the expression of pyroptosis related genes (PRGs) and prognosis of hepatocellular carcinoma (HCC). In this study, a specific PRGs prognostic model was developed with an aim to improve therapeutic efficiency among HCC patients. In total, 42 PRGs that were differentially expressed between HCC tissues and adjacent tissues and we exhibited the mutation frequency, classification, the location of copy number variation (CNV) alteration and the CNV variation frequency of PRGs. Two clusters were distinguished by the consensus clustering analysis based on the 42 differentially expressed genes (DEGs). There were significant differences in clinical features including T stage, grade, gender, and stage among different clusters. Kaplan–Meier curve analysis showed that cluster 1 had a better prognosis than cluster 2. The prognostic value of PRGs for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. Based on the univariate analysis and multivariate analysis, a 10-gene signature was built and all HCC patients in the TCGA cohort were divided into low-risk group and high-risk group. HCC patients in the high-risk group showed significantly lower survival possibilities than those in the low-risk group (P < 0.001). Utilizing the median risk score from the TCGA cohort, HCC patients from International Cancer Genome Consortium (ICGC)-LIRI-JP cohort and Gene Expression Omnibus (GEO) cohort (GSE14520) were divided into two risk subgroups. The result showed that overall survival (OS) time was decreased in the high-risk group. Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of HCC patients. Then, ROC curve and survival analysis were performed to evaluate the prognostic prediction value of the model. Finally, we constructed a PRGs clinical characteristics nomogram to further predict HCC patient survival probability. There were significant differences in immune cell infiltration, GSEA enrichment pathway, IC50 of chemotherapeutics, PRGs mutation frequency between high-risk group and low-risk group. This work suggests PRGs signature played a crucial role in predicting the prognosis, infiltration of cancer microenvironment, and sensitivity of chemotherapeutic agents.

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“…Copy number amplification was detected while its expression was significantly differentiated among HCC and the neighboring healthy tissue. Concerning the predictive value of NLRP3, the highest expression of NLRP3 was associated with poor OS [96].…”

Section: The Nlrp3 As Biomarkermentioning

confidence: 97%

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

Papadakos

Dedes

Kouroumalis

et al. 2022

Cancers

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The HCC constitutes one of the most frequent cancers, with a non-decreasing trend in disease mortality despite advances in systemic therapy and surgery. This trend is fueled by the rise of an obesity wave which is prominent the Western populations and has reshaped the etiologic landscape of HCC. Interest in the nucleotide-binding domain leucine-rich repeat containing (NLR) family member NLRP3 has recently been revived since it would appear that, by generating inflammasomes, it participates in several physiologic processes and its dysfunction leads to disease. The NLRP3 inflammasome has been studied in depth, and its influence in HCC pathogenesis has been extensively documented during the past quinquennial. Since inflammation comprises a major regulator of carcinogenesis, it is of paramount importance an attempt to evaluate the contribution of the NLRP3 inflammasome to the generation and management of HCC. The aim of this review was to examine the literature in order to determine the impact of the NLRP3 inflammasome on, and present a hypothesis about its input in, HCC.

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A Pyroptosis-Related Gene Signature to Predict Patients’ Prognosis and Immune Landscape in Liver Hepatocellular Carcinoma

Cited by 9 publications

References 40 publications

Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

Identification and Validation of Two Heterogeneous Molecular Subtypes and a Prognosis Predictive Model for Hepatocellular Carcinoma Based on Pyroptosis

Pyroptosis related genes signature predicts prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma

The Role of the NLRP3 Inflammasome in HCC Carcinogenesis and Treatment: Harnessing Innate Immunity

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