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

Zhao, Yidi; Song, Qingya; Xu, Fangshi; Zhou, Yang; Zuo, Xiaoli; Zhang, Zhengliang

doi:10.3389/fgene.2022.823443

Cited by 7 publications

(6 citation statements)

References 59 publications

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“…In the end, we demonstrated that the risk score could be employed as a standalone indicator judging the prognosis of BLCA, and the HR value of risk score was much higher than HR value of age and tumor stage, which indicated that it was more meaningful to evaluate the BLCA patients’ prognosis by risk score than by age and tumor stage. Similar results have been reported in other cancer studies [ 54 , 55 ]. A nomogram is recognized as a convenient method to speculate the survival probability of patients [ 56 , 57 , 58 ].…”

Section: Discussionsupporting

confidence: 92%

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

et al. 2022

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The purpose of this study was to explore the relationship between bladder urothelial cancer (BLCA) and immunity, to screen prognosis-related immune genes (PIGs), and to construct an immune-related prognosis model (IRPM). We processed the relevant data of The Cancer Genome Atlas (TCGA-BLCA) and GSE13507 using R software and Perl. We divided BLCA into high-immunity and low-immunity subtypes. There were significant differences in the two subtypes. In addition, we identified 13 PIGs of BLCA by jointly analyzing the gene expression data and survival information of GSE13507 and TCGA-BLCA, and constructed IRPM through nine of them. The low-risk group had better survival outcome than the high-risk group. We also constructed a nomogram based on clinicopathological information and risk scores of the patients. Moreover, the prognosis of BLCA patients was significantly impacted by the expression of almost every gene used to calculate the risk score. The result of real-time fluorescence quantitative polymerase chain reaction revealed that all the genes used to calculate the risk score were differentially expressed between BLCA and adjacent normal tissues, except PDGFRA. Our research provided potential targets for the treatment of BLCA and a reference for judging the prognosis of BLCA.

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Section: Discussionsupporting

confidence: 92%

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

et al. 2022

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“…Interestingly, WNK1 triggers the progression and invasion of HCC cell lines and xenograft tumors via its interaction with lncRNAs in the tumor microenvironment 64 . On the other hand, inhibition of WNK1 diminished its stimulative capabilities on proliferation, invasion, and migration in HCC cells, which is suggested to be mediated via activating AMPK and autophagy 32,65 . Nonetheless, the functional significance of WNK1 in lenvatinib resistance in HCC was neither reported nor anticipated.…”

Section: Discussionmentioning

confidence: 99%

“…64 On the other hand, inhibition of WNK1 diminished its stimulative capabilities on proliferation, invasion, and migration in HCC cells, which is suggested to be mediated via activating AMPK and autophagy. 32,65 Nonetheless, the functional significance of WNK1 in lenvatinib resistance in HCC was neither reported nor anticipated.…”

Section: Discussionmentioning

confidence: 99%

Focal adhesion kinase confers lenvatinib resistance in hepatocellular carcinoma via the regulation of lysine‐deficient kinase 1

Hou,

Gad,

Ding

et al. 2023

Molecular Carcinogenesis

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Lenvatinib is a clinically effective multikinase inhibitor approved for first‐line therapy of advanced hepatocellular carcinoma (HCC). Although resistance against lenvatinib often emerges and limits its antitumor activity, the underlying molecular mechanisms involved in endogenous and acquired resistance remain elusive. In this study, we identified focal adhesion kinase (FAK) as a critical contributor to lenvatinib resistance in HCC. The elevated expression and phosphorylation of FAK were observed in both acquired and endogenous lenvatinib‐resistant (LR) HCC cells. Furthermore, inhibition of FAK reversed lenvatinib resistance in vitro and in vivo. Mechanistically, FAK promoted lenvatinib resistance through regulating lysine‐deficient kinase 1 (WNK1). Phosphorylation of WNK1 was significantly increased in LR‐HCC cells. Further, WNK1 inhibitor WNK463 resensitized either established or endogenous LR‐HCC cells to lenvatinib treatment. In addition, overexpression of WNK1 desensitized parental HCC cells to lenvatinib treatment. Conclusively, our results establish a crucial role and novel mechanism of FAK in lenvatinib resistance and suggest that targeting the FAK/WNK1 axis is a promising therapeutic strategy in HCC patients showing lenvatinib resistance.

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“…HCC cells with different drug sensitivity were used for in vitro validation. We compared the C-index values of several latest prediction signatures in HCC with ours ( Lin et al, 2022 ; Miao et al, 2022 ; Ye et al, 2022 ; Zhao et al, 2022 ; Zhou et al, 2022 ) ( Supplementary Figure S2 ). Genes in the prediction signature are listed in Supplementary File S4 .…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Necroptosis-Related LncRNA Signature in Hepatocellular Carcinoma for Prognosis Estimation and Microenvironment Status

Chen

et al. 2022

Front. Genet.

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Background: Hepatocellular carcinoma (HCC) is among malignancies with the highest fatality toll globally and minimal therapeutic options. Necroptosis is a programmed form of necrosis or inflammatory cell death, which can affect prognosis and microenvironmental status of HCC. Therefore, we aimed to explore the prognostic value of necroptosis-related lncRNAs (NRLs) in HCC and the role of the tumor microenvironment (TME) in immunotherapy.Methods: The RNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). NRLs were identified by Pearson correlation analysis. The signature was constructed using the LASSO–Cox regression analysis and evaluated using the receiver operating characteristic curve (ROC) and the area under the Kaplan–Meier curve. The nomogram was built based on clinical information and risk score. Gene set enrichment analysis (GSEA), immunoassay, half-maximum inhibitory concentration (IC50) analysis of the risk group, and the HCC subtype identification based on NRLs were also carried out. Finally, we detected the expression of lncRNAs in HCC tissues and cell lines in vitro.Results: A total of 508 NRLs were screened out, and seven NRLs were constructed as a risk stratification system to classify patients into distinct low- and high-risk groups. Patients in the high-risk group had a significantly lower overall survival (OS) than those in the low-risk group. Using multivariate Cox regression analysis, we found that the risk score was an independent predictor of OS. Functional analysis showed that the immune status of different patients was different. The IC50 analysis of chemotherapy demonstrated that patients in the high-risk group were more sensitive to commonly prescribed drugs. qRT-PCR showed that three high-risk lncRNAs were upregulated in drug-resistant cells, and the expression in HCC tissues was higher than that in adjacent tissues.Conclusion: The prediction signature developed in this study can be used to assess the prognosis and microenvironment of HCC patients, and serve as a new benchmark for HCC treatment selection.

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

Cited by 7 publications

References 59 publications

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

Identification of Immune-Related Subtypes and Construction of a Novel Prognostic Model for Bladder Urothelial Cancer

Focal adhesion kinase confers lenvatinib resistance in hepatocellular carcinoma via the regulation of lysine‐deficient kinase 1

Identification and Validation of Necroptosis-Related LncRNA Signature in Hepatocellular Carcinoma for Prognosis Estimation and Microenvironment Status

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