Pan-Cancer Analysis of the Characteristics of LY96 in Prognosis and Immunotherapy Across Human Cancer

Nie, Kechao; Li, Jing; Peng, Luqi; Zhang, Mei; Huang, Wei

doi:10.3389/fmolb.2022.837393

Cited by 14 publications

(11 citation statements)

References 33 publications

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“…VCAN-AS1 interacts with eIF4A3 to downregulate TP53 expression and might be a potential cancer therapy target (Feng et al, 2020); AC131391.1 and AL139147.1 were firstly discovered. Whereas AL139147.1 showed a novel positive correlation with ENTPD1 (CD39) and IL1R1 (Figure 3F), which are involved in tumor immune cells infiltration and tumor microenvironment alteration (Krishna et al, 2020;; AC131391.1 correlated with LY96, which plays a vital role in tumorigenesis by modulating host immunity (Nie et al, 2022). The newly discovered lncRNA knowledge about ICD might help us bring a breakthrough into clinical practice by improving our mechanistic understanding of STAD.…”

Section: Discussionmentioning

confidence: 95%

Prognostic value of antitumor drug targets prediction using integrated bioinformatic analysis for immunogenic cell death-related lncRNA model based on stomach adenocarcinoma characteristics and tumor immune microenvironment

Ding

Zhao

et al. 2022

Front. Pharmacol.

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Stomach adenocarcinoma (STAD) ranks as the fourth prevalent cause of mortality worldwide due to cancer. The prognosis for those suffering from STAD was bleak. Immunogenic cell death (ICD), a form of induced cellular death that causes an adaptive immune response and has increasing in anticancer treatment. However, it has not been ascertained how ICD-related lncRNAs affect STAD. Using univariate Cox regression and the TCGA database, lncRNAs with prognostic value were identified. Thereafter, we created a prognostic lncRNA-based model using LASSO. Kaplan-Meier assessment, time-dependent receiver operating characteristic (ROC) analyzation, independent prognostic investigation, and nomogram were used to assess model correctness. Additional research included evaluations of the immunological microenvironment, gene set enrichment analyses (GSEA), tumor mutation burdens (TMBs), tumor immune dysfunctions and exclusions (TIDEs), and antitumor compounds IC50 predictions. We found 24 ICD-related lncRNAs with prognostic value via univariate Cox analysis (p < 0.05). Subsequently, a risk model was proposed using five lncRNAs relevant to ICD. The risk signature, correlated with immune cell infiltration, had strong predictive performance. Individuals at low-risk group outlived those at high risk (p < 0.001). An evaluation of the 5-lncRNA risk mode including ROC curves, nomograms, and correction curves confirmed its predictive capability. The findings of functional tests revealed a substantial alteration in immunological conditions and the IC50 sensitivity for the two groups. Using five ICD-related lncRNAs, the authors developed a new risk model for STAD patients that could predict their cumulative overall survival rate and guide their individual treatment.

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Section: Discussionmentioning

confidence: 95%

Prognostic value of antitumor drug targets prediction using integrated bioinformatic analysis for immunogenic cell death-related lncRNA model based on stomach adenocarcinoma characteristics and tumor immune microenvironment

Ding

Zhao

et al. 2022

Front. Pharmacol.

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“…LY96 is significantly upregulated and can be used as a prognostic factor in most types of cancers. LY96 is related to DNA methylation, copy number, microsatellite instability (MSI), somatic mutation, tumor mutation burden (TMB), tumor microenvironment (TME) features and immune cell infiltration in cancers, and LY96 can contribute to drug resistance and regulate classic tumor-associated pathways ( Nie et al, 2022 ). We found the prognostic model constructed by the 6 ICD associated genes could predict the prognosis as well as 1 year, 3 years, and 5 years survival status well.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma

Xiang

Liu

et al. 2023

Front. Pharmacol.

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Background: Immunogenic cell death (ICD) plays an important role in the development of cancers. This study attempted to explore the role of ICD in the prognosis of hepatocellular carcinoma (HCC).Methods: Gene expression and clinical data were downloaded from The Cancer Genome Alas and Gene Expression Omnibus dataset. The immune/stromal/Estimate scores of the tumor microenvironment (TME) were calculated by ESTIMATE and CIBERSORT algorithms. Kaplan-Meier analysis, functional enrichment analysis, least absolute shrinkage and selection operator (LASSO) analysis, and univariate and multivariate Cox regression analysis were used for prognostic gene screening and prognostic model construction. The correlation of immune cell infiltration and risk scores was analyzed as well. Molecular docking was used to explore the relevance of related genes to anti-cancer drugs.Results: Ten ICD associated differentially expressed genes in HCC were found, and all of them had good predictive ability for HCC. ICD gene high amount of expression group was associated with poor prognosis (p = 0.015). The TME, immune cell infiltration and gene expression were different between ICD high and low groups (all p < 0.05). Six ICD associated genes (BAX, CASP8, IFNB1, LY96, NT5E and PIK3CA) which could predict the survival status were identified and used to construct the prognostic model for HCC. A risk score was calculated and it could be used as an independent prognostic factor in HCC patients (p < 0.001). In addition, the risk score had a positive correlation with macrophage M0 (r = 0.33, p = 0.0086). Molecular docking indicated that sorafenib could bind strongly to the target protein, representing that sorafenib may exert anticancer effects through these six ICD associated genes.Conclusion: This study established a prognostic model including six ICD associated genes for HCC, which may deepen our understanding of ICD and guide therapy for HCC patients.

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“…The role of IL6 in regulating ICD in HGGs may be therapy-related and rely on cell-extrinsic niche factors. Lymphocyte antigen 96 (LY96 or MD2), which is from the toll-like receptor 4 (TLR4) signaling pathway, promotes the development of immunotherapy and targeted therapy of malignancies in tumor occurrence and progression [ 40 ]. However, other studies have pointed out that LY96 inhibition would prevent TLR4-mediated inflammatory responses and metastatic cancer growth [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Upregulated Immunogenic Cell-Death-Associated Gene Signature Predicts Reduced Responsiveness to Immune-Checkpoint-Blockade Therapy and Poor Prognosis in High-Grade Gliomas

Tang

Guo

Yang

et al. 2022

Cells

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Background: Immunogenic cell death (ICD) has emerged as a potential mechanism mediating adaptive immune response and tumor immunity in anti-cancer treatment. However, the signature of ICD in high-grade gliomas (HGGs) remains largely unknown, and its relevance to immunotherapies is still undetermined. The purpose of this study is to identify ICD-associated genotypes in order to explore their relevance to tumor immunity, patient prognosis and therapeutic efficacy of immune checkpoint blockade (ICB) therapy in HGGs. Methods: Bulk RNA-seq data and clinical information on 169 and 297 patients were obtained from the Cancer Genome Atlas (TCGA) and China Glioma Genome Atlas (CGGA), respectively. The functional enrichment and characterization of ICD genotyping were detected, and the ICD prognostic signature prediction model was constructed using least absolute shrinkage and selection operator (LASSO) regression. The responsiveness to immunotherapy was predicted according to the scoring of the ICD prognostic signature. Results: The HGG patients with high ICD gene signature (C1) showed poor outcomes, increased activity of immune modulation and immune escape, high levels of immune-checkpoint markers, and HLA-related genes, which may explain their reduced response to ICB immunotherapy. A gene set of the ICD signature, composing FOXP3, IL6 LY96, MYD88 and PDIA3, showed an independent prognostic value in both the TCGA and the CGGA HGG cohort. Conclusions: Our in silico analyses identified the ICD gene signature in HGGs with potential implications for predicting the responsiveness to ICB immune therapy and patient outcomes.

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Pan-Cancer Analysis of the Characteristics of LY96 in Prognosis and Immunotherapy Across Human Cancer

Cited by 14 publications

References 33 publications

Prognostic value of antitumor drug targets prediction using integrated bioinformatic analysis for immunogenic cell death-related lncRNA model based on stomach adenocarcinoma characteristics and tumor immune microenvironment

Prognostic value of antitumor drug targets prediction using integrated bioinformatic analysis for immunogenic cell death-related lncRNA model based on stomach adenocarcinoma characteristics and tumor immune microenvironment

Comprehensive analysis of immunogenic cell death associated genes expression, tumor microenvironment, and prognosis in hepatocellular carcinoma

Upregulated Immunogenic Cell-Death-Associated Gene Signature Predicts Reduced Responsiveness to Immune-Checkpoint-Blockade Therapy and Poor Prognosis in High-Grade Gliomas

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