Identification of pyroptosis‐related lncRNAs for constructing a prognostic model and their correlation with immune infiltration in breast cancer

Lv, Wenchang; Tan, Yufang; Zhao, Chongru; Wang, Yichen; Wu, Min; Wu, Yiping; Ren, Yuping; Zhang, Qi

doi:10.1111/jcmm.16969

Cited by 17 publications

(17 citation statements)

References 45 publications

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“…Hydrogen inhibits endometrial cancer progression by activating the CASP1/GSDMD-mediated pyroptosis pathway ( Yang et al, 2020 ). To date, some studies have explored the roles of pyroptosis regulatory genes (PRGs) in endometrial cancer ( Zhang and Yang 2021 ), ovarian cancer ( Ye et al, 2021 ), and breast cancer ( Lv et al, 2021 ). These findings undoubtedly point toward the fact that pyroptosis profoundly affects the prognosis and immune process in multiple cancers.…”

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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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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“…Nowadays, it has been proved that lncRNAs engage in cancer‐related cellular pathways and have good predictive power in prognosis and diagnosis 22,23 . Emerging studies have tried to establish novel and effective lncRNAs pattern risk models in malignancy, 24,25 as well as discover molecular character and potential therapy targets of breast cancer patients 26,27 . Until now, the patterns of necroptosis‐related lncRNAs in BC and the potential capability of predicting the prognosis has not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Necroptosis‐related lncRNA to establish novel prognostic signature and predict the immunotherapy response in breast cancer

Chen

Yang²,

Fang

et al. 2022

Clinical Laboratory Analysis

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Background: Necroptosis is a type of programmed cell death, and recent researches have showed that lncRNAs could regulate the process of necroptosis in multiple cancers. We tried to screen necroptosis-related lncRNAs and investigate the immune landscape in breast cancer (BC). Methods:The samples of breast normal and cancer tissue were acquired from TCGA and GTEx databases. A risk prognostic model was constructed based on the identified necroptosis-related lncRNAs by Cox regression and least absolute shrinkage and selection operator (LASSO) method. Moreover, the forecast performance of this model was verified and accredited by synthetic approach. Subsequently, an accurate nomogram was constructed to predict the prognosis of BC patients. The biological differences were investigated through GO, GSEA, and immune analysis. The immunotherapy response was estimated through tumor mutation burden (TMB) and tumor immune dysfunction and exclusion (TIDE) score.Results: A total of 251 necroptosis-related lncRNAs were identified by differential coexpression analysis, and SH3BP5-AS1, AC012073.1, AC120114.1, LINC00377, AL133467.1, AC036108.3, and AC020663.2 were involved in the risk model, which had an excellent concordance with the prediction. The pathway analyses showed that immune-related pathways were relevant to the necroptosis-related lncRNAs risk model. And the risk score was significantly correlated with immune cell infiltration, as well as the ESTIMATE score. Most notably, the patients of higher risk score were characterized with increased TMB and decreased TIDE score, indicating that these patients showed better immune checkpoint blockade response. Conclusion:These findings were conducive to understand the function of necroptosisrelated lncRNAs in BC and provide a potential promising therapeutic strategy for BC.

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“…Current studies have shown that the occurrence of tumor is closely related to the pyroptosis, which has a certain inhibitory effect on the emergence and growth of tumors in a variety of cancers, such as lung cancer, leukemia, melanoma and other tumors [16][17][18][19][20][21][22][23][24][25][26][27] . pyroptosis has a certain expression in the genes of BC patients, and the relevant literature has introduced and information mining [11][12][13][28][29][30] . In the study of BC, the over expression of GSDMB is related with poorer prognosis and tumorous progression [31] .…”

Section: Discussionmentioning

confidence: 99%

“…The ROC curve analysis of GEO and TCGA cohorts demonstrates that our prognostic model has good performance (Figure 5K-L). Furthermore, ROC data were collected from other literatures [11][12][13] on BC prognostic model of final significant prognosis-related genes. After extracting the same data set GSE42568, a horizontal comparison was made.…”

Section: Evaluation and Analysis Of The Risk Modelmentioning

confidence: 99%

A Novel Prognosis Model based on Comprehensive Analysis of Pyroptosis-Related Genes in Breast Cancer

Zeng

Wang

Yang

2022

Preprint

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Background: Pyroptosis plays a dual role in cancer. It can not only induce chronic tumor necrosis, but also stimulate acute inflammation to enhance immune response. However, the study of cell pyroptosis in Breast Cancer (BC) is still limited. Methods: A total of 26 pyroptosis-related differential genes were obtained, and PPI network and correlation analysis were demonstrated as well. Besides, 3 pyroptosis-related prognostic genes were collected by the univariate COX analysis. Through these 3 genes, patients were clustered into 2 sub-types by the Consensus clustering, then the EM and XMeans were also carried out to recheck the result. Furthermore, the significant prognosis-related genes were obtained by the Random Forest and LASSO analysis. Based on the above, the corresponding weights were calculated through the univariate and multivariate Cox analysis, and the prognostic model was constructed. In addition, the ROC curve, risk curve, PCA, t-SNE, COX, GO, KEGG and ssGSEA were analyzed, respectively. Results: Through the verification of 3 different clustering algorithms, 2 sub-types of BC were obtained. Furthermore, 'ELOVL2', 'IGLV6-57', 'FGBP1', 'HLA-DPB2' with weights of -0.183, -0.101, -0.227 and -0.254 were employed to establish the prognostic model. Validation shows that our model has good effect and the Go KEGG and Immune microenvironment analysis showed the enrichment of the differential genes. Conclusion: Our study identified 4 genes that are closely correlated with the overall survival of BC patients, and the prognostic model can effectively divide patients into high- and low-risk groups, which may have certain guiding significance for prognosis.

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Identification of pyroptosis‐related lncRNAs for constructing a prognostic model and their correlation with immune infiltration in breast cancer

Cited by 17 publications

References 45 publications

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

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

Necroptosis‐related lncRNA to establish novel prognostic signature and predict the immunotherapy response in breast cancer

A Novel Prognosis Model based on Comprehensive Analysis of Pyroptosis-Related Genes in Breast Cancer

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