Necroptosis and tumor progression

Yan, Jiong; Wan, Pin; Choksi, Swati; Liu, Zheng-gang

doi:10.1016/j.trecan.2021.09.003

Cited by 218 publications

(157 citation statements)

References 51 publications

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“…With additional research, another mechanism of cell death, necroptosis (programmed necrosis), was discovered in 1988 as a type of programmed death and was named in 2005 ( Laster et al, 1988 ; Degterev et al, 2005 ). Necroptosis is thought to be important in tumor regulation, including tumorigenesis, tumor immunity, and tumor metastasis ( Stoll et al, 2017 ; Seehawer et al, 2018 ; Yan et al, 2021 ). Necroptosis plays a dual role in tumor regulation, not only promoting tumor progression and metastasis ( Park et al, 2009 ; McCormick et al, 2016 ; Strilic et al, 2016 ) but also preventing tumor progression ( Feng et al, 2015 ; Höckendorf et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

Liu

Huang

Chen

et al. 2022

Front. Mol. Biosci.

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Colon cancer (CC) is one of the most frequent malignancies in the world, with a high rate of morbidity and death. In CC, necroptosis and long noncoding RNA (lncRNAs) are crucial, but the mechanism is not completely clear. The goal of this study was to create a new signature that might predict patient survival and tumor immunity in patients with CC. Expression profiles of necroptosis-related lncRNAs in 473 patients with CC were retrieved from the TCGA database. A consensus clustering analysis based on differentially expressed (DE) genes and a prognostic model based on least absolute shrinkage and selection operator (LASSO) regression analysis were conducted. Clinicopathological correlation analysis, expression difference analysis, PCA, TMB, GO analysis, KEGG enrichment analysis, survival analysis, immune correlation analysis, prediction of clinical therapeutic compounds, and qRT–PCR were also conducted. Fifty-six necroptosis-related lncRNAs were found to be linked to the prognosis, and consensus clustering analysis was performed. There were substantial variations in survival, immune checkpoint expression, clinicopathological correlations, and tumor immunity among the different subgroups. Six lncRNAs were discovered, and patients were split into high-risk and low-risk groups based on a risk score generated using these six lncRNAs. The survival time of low-risk patients was considerably longer than that of high-risk patients, indicating that these lncRNAs are directly associated with survival. The risk score was associated with the tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. After univariate and multivariate Cox regression analysis, the risk score and tumor stage remained significant. Cancer- and metabolism-related pathways were enriched by KEGG analyses. Immune infiltration was shown to differ significantly between high- and low-risk patients in a tumor immunoassay. Eight compounds were screened out, and qRT–PCR confirmed the differential expression of the six lncRNAs. Overall, in CC, necroptosis-related lncRNAs have an important function, and the prognosis of patients with CC can be predicted by these six necroptosis-related lncRNAs. They may be useful in the future for customized cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

Liu

Huang

Chen

et al. 2022

Front. Mol. Biosci.

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“…Recent studies have indicated that necroptosis has an important role in tumorigenesis, tumor metastasis, and tumoral immune response ( Gong et al, 2019 ). Of note is the fact that necroptosis appears to be antitumorigenic or protumorigenic, depending on the tumor type and conditions during tumorigenesis ( Yan et al, 2022 ). RIPK3 may restrict myeloid leukemogenesis and the differentiation of leukemia-initiating cells by promoting RIPK3–MLKL-mediated necroptosis ( Höckendorf et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel Necroptosis-Related lncRNA Signature Predicts the Prognosis of Lung Adenocarcinoma

Luo

Wang

et al. 2022

Front. Genet.

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Background: Necroptosis is closely related to the tumorigenesis and development of cancer. An increasing number of studies have demonstrated that targeting necroptosis could be a novel treatment strategy for cancer. However, the predictive potential of necroptosis-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD) still needs to be clarified. This study aimed to construct a prognostic signature based on necroptosis-related lncRNAs to predict the prognosis of LUAD.Methods: We downloaded RNA sequencing data from The Cancer Genome Atlas database. Co-expression network analysis, univariate Cox regression, and least absolute shrinkage and selection operator were adopted to identify necroptosis-related prognostic lncRNAs. We constructed the predictive signature by multivariate Cox regression. Kaplan–Meier analysis, time-dependent receiver operating characteristics, nomogram, and calibration curves were used to validate and evaluate the signature. Subsequently, we used gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) to explore the relationship between the predictive signature and tumor immune microenvironment of risk groups. Finally, the correlation between the predictive signature and immune checkpoint expression of LUAD patients was also analyzed.Results: We constructed a signature composed of 7 necroptosis-related lncRNAs (AC026355.2, AC099850.3, AF131215.5, UST-AS2, ARHGAP26-AS1, FAM83A-AS1, and AC010999.2). The signature could serve as an independent predictor for LUAD patients. Compared with clinicopathological variables, the necroptosis-related lncRNA signature has a higher diagnostic efficiency, with the area under the receiver operating characteristic curve being 0.723. Meanwhile, when patients were stratified according to different clinicopathological variables, the overall survival of patients in the high-risk group was shorter than that of those in the low-risk group. GSEA showed that tumor- and immune-related pathways were mainly enriched in the low-risk group. ssGSEA further confirmed that the predictive signature was significantly related to the immune status of LUAD patients. The immune checkpoint analysis displayed that low-risk patients had a higher immune checkpoint expression, such as CTLA-4, HAVCR2, PD-1, and TIGIT. This suggested that immunological function is more active in the low-risk group LUAD patients who might benefit from checkpoint blockade immunotherapies.Conclusion: The predictive signature can independently predict the prognosis of LUAD, helps elucidate the mechanism of necroptosis-related lncRNAs in LUAD, and provides immunotherapy guidance for patients with LUAD.

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“…Consequently, cell necrosis plays a significant role in tumorigenesis, metastasis, and infectious and inflammatory disorders [8,9]. Necroptosis promotes cancer spread, although it could suppress cancer [10][11][12]. However, only a few sequence-based studies on aberrant gene expression and its relationship with overall survival (OS) in PAAD patients with necroptosis have been conducted.…”

Section: Introductionmentioning

confidence: 99%

Novel necroptosis-related gene signature for predicting the prognosis of pancreatic adenocarcinoma

Huang

Cai

et al. 2022

Aging

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Pancreatic adenocarcinoma (PAAD) is a deadly digestive system tumor with a poor prognosis. Recently, necroptosis has been considered as a type of inflammatory programmed cell death. However, the expression of necroptosis-related genes (NRGs) in PAAD and their associations with prognosis remain unclear. NRGs' prediction potential in PAAD samples from The TCGA and GEO datasets was investigated. The prediction model was constructed using Lasso regression. Co-expression analysis showed that gene expression was closely related to necroptosis. NRGs were shown to be somewhat overexpressed in high-risk people even when no other clinical symptoms were present, indicating that they may be utilized in a model to predict PAAD prognosis. GSEA showed immunological and tumor-related pathways in the high-risk group. Based on the findings, immune function and m6A genes differ significantly between the low-risk and high-risk groups. MET, AM25C, MROH9, MYEOV, FAM111B, Y6D, and PPP2R3A might be related to the oncology process for PAAD patients. Moreover, CASKIN2, TLE2, USP20, SPRN, ARSG, MIR106B, and MIR98 might be associated with low-risk patients with PAAD. NRGs and the relationship of the immune function, immune checkpoints, and m6A gene expression with NRGs in PAAD may be considered as potential therapeutic targets that should be further studied.

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Necroptosis and tumor progression

Cited by 218 publications

References 51 publications

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

Comprehensive Analysis of Necroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients With Colon Cancer

A Novel Necroptosis-Related lncRNA Signature Predicts the Prognosis of Lung Adenocarcinoma

Novel necroptosis-related gene signature for predicting the prognosis of pancreatic adenocarcinoma

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