Identification of an Autophagy-Related Risk Signature Correlates With Immunophenotype and Predicts Immune Checkpoint Blockade Efficacy of Neuroblastoma

Kang, Wenjuan; Hu, Jiajian; Zhao, Qiang; Song, Fengju

doi:10.3389/fcell.2021.731380

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…In this study, the immune checkpoint gene CD274 was negatively correlated with the risk score, and the level expression of CD274 was higher in the low-risk group. The conclusion is consistent with other studies [ 49 ]. The result suggests that the low-risk group has a better therapeutic effect on anti-PD-L1 therapy.…”

Section: Discussionsupporting

confidence: 94%

A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma

Zhang

Xia

et al. 2022

BMC Med Genomics

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Background MYCN amplification (MNA) has been proved to be related to poor prognosis in neuroblastoma (NBL), but the MYCN-related immune signatures and genes remain unclear. Methods Enrichment analysis was used to identify the significant enrichment pathways of differentially expressed immune-related genes (DEIRGs). Weight gene coexpression network analysis (WGCNA) was applied to reveal the correlation between these DEIRGs and MYCN status. Univariate and multivariate Cox analyses were used to construct risk model. The relevant fractions of immune cells were evaluated by CIBERSORT and single-sample gene set enrichment analysis (ssGSEA). Results Five genes, including CHGA, PTGER1, SHC3, PLXNC1, and TRIM55 were enrolled into the risk model. Kaplan–Meier survival analysis and receiver operating characteristic (ROC) curve showed that our model performed well in predicting the outcomes of NBL (3-years AUC = 0.720, 5-year AUC = 0.775, 10-years AUC = 0.782), which has been validated in the GSE49711 dataset and the E-MTAB-8248 dataset. By comparing with the tumor immune dysfunction and exclusion (TIDE) and tumor inflammation signature (TIS), we further proved that our model is reliable. Univariate and multivariate Cox regression analyses indicated that the risk score, age, and MYCN can serve as independent prognostic factors in the E-MATB-8248. Functional enrichment analysis showed the DEIRGs were enriched in leukocyte adhesion-related signaling pathways. Gene set enrichment analysis (GSEA) revealed the significantly enriched pathways of the five MYCN-related DEIRGs. The risk score was negatively correlated with the immune checkpoint CD274 (PD-L1) but no significant difference with the TMB. We also confirmed the prognostic value of our model in predicting immunotherapeutics. Conclusion We constructed and verified a signature based on DEIRG that related to MNA and predicted the survival of NBL based on relevant immune signatures. These findings could provide help for predicting prognosis and developing immunotherapy in NBL.

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Section: Discussionsupporting

confidence: 94%

A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma

Zhang

Xia

et al. 2022

BMC Med Genomics

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“…These reports show that lactate is a promising research object in the process of tumor development and treatment. At present, more and more studies have designed different signatures to predict the prognosis of tumor patients according to different biological modi cations, such as ferroptosis (6), apoptosis (56), autophagy (57), and glycolysis(58). Although the current researches have shown that lactate is closely related to tumors and the TME, there is no report about designing a lactate-related signature to predict patients' prognosis and its relationship to TME.…”

Section: Discussionmentioning

confidence: 99%

A Novel Defined Risk Signature Based on Lactate-Related Genes can Predicts Prognosis of Bladder Cancer

Jin

et al. 2022

Preprint

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Background Lactate is an important carbon source for cell metabolism as well as a signaling molecule in normal, chronic inflammatory and cancer tissues. However, the relationship between lactate and bladder cancer (BLCA) has not been studied yet. Methods Expression profiles of the patients with bladder cancer from The Cancer Genome Atlas were divided into different clusters using non-negative matrix factorization clustering to obtain differentially expressed genes (DEGs). Univariate Cox analysis, Lasso-Cox analysis, Kaplan-Meier survival analysis, and time-dependent receiver operating characteristics curves were used to developed and validated a prognostic signature for the survival rate of patients. "CIBERSORT" and "ESTIMATE" algorithms were used to quantify the immunocyte content and evaluate tumor purity for different clusters and subgroups. Online tool "Tumor Immune Dysfunction and Exclusion" was used to predict the immune escape ability of patients in different scoring subgroups after immunotherapy. Results The different clusters according to the expression pattern of lactate-associated genes (LAGs) had significant differences in the survival rate and the tumor microenvironment. Besides, a risk signature constructed by DEGs based on different clusters and verified by the GSE32894 dataset could not only significantly distinguish between the prognosis and clinical features of patients with different scores but was also found to be related to the tumor microenvironment and immunotherapy. Finally, a high accuracy nomogram model was established. Conclusions Overall, this research has revealed the relationship between lactate and patient prognosis, tumor microenvironment, and immunotherapy, which may provide novel prognostic biomarkers for patients with BLCA.

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“…A total of thirty-three ganglioside-related genes were extracted from the GSE49710 dataset. Given the significant difference between International Neuroblastoma Staging System (INSS) stage 4 and other stages ( 24 ), seventeen ganglioside-related genes were identified as differentially expressed genes (DEGs) between these two groups. Unsupervised consensus clustering analysis based on ganglioside-related DEGs was performed on GSE49710 and TARGET datasets using the “Consensus Cluster Plus” R package and the “k-means” method to discern diverse expression patterns, with the repetition number set to 1000 to ensure stability ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response

et al. 2022

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IntroductionGangliosides play an essential role in cancer development and progression. However, the involvement of gangliosides in the prognosis and tumor microenvironment (TME) of neuroblastoma is not entirely understood.MethodsConsensus clustering analysis was performed to identify ganglioside-mediated molecular subtypes. LASSO-Cox analysis was conducted to identify independent prognostic genes, and a novel risk signature was constructed. The risk signature was validated internally and externally. We further explored the independent prognosis value, immune landscape, drug susceptibility, and tumor dedifferentiation of the risk signature. The role of the signature gene B3GALT4 in neuroblastoma was explored in vitro.ResultsSeventeen ganglioside-related genes were differentially expressed between INSS stage 4 and other stages, and two ganglioside-related clusters with distinct prognoses were identified. A novel risk signature integrating ten ganglioside-related prognostic genes was established. Across the train set and external validation sets, the risk signature presented high predictive accuracy and discrimination. The risk signature was an independent prognostic factor and constructed a nomogram combining multiple clinical characteristics. In the high-score group, the deficiency in antigen processing and presenting machinery, lack of immune cell infiltration, and escaping NK cells contributed substantially to immune escape. The low-score group was more responsive to immune checkpoint blockade therapy, while the high-score group showed substantial sensitivity to multiple chemotherapeutic drugs. Besides, the risk score was significantly positively correlated with the stemness index and reduced considerably in all-trans retinoic acid-treated neuroblastoma cell lines, indicating high dedifferentiation in the high-score group. Additionally, neuroblastoma cells with downregulation of B3GALT4 present with increased proliferation, invasion, and metastasis abilities in vitro.ConclusionThe novel ganglioside-related risk signature highlights the role of ganglioside in neuroblastoma prognosis and immune landscape and helps optimize chemotherapy and immunotherapy for neuroblastoma.

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Identification of an Autophagy-Related Risk Signature Correlates With Immunophenotype and Predicts Immune Checkpoint Blockade Efficacy of Neuroblastoma

Cited by 4 publications

References 57 publications

A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma

A signature based on five immune-related genes to predict the survival and immune characteristics of neuroblastoma

A Novel Defined Risk Signature Based on Lactate-Related Genes can Predicts Prognosis of Bladder Cancer

A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response

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