Analysis of Tumor Glycosylation Characteristics and Implications for Immune Checkpoint Inhibitor’s Efficacy for Breast Cancer

Lv, Wenchang; Yu, Honghao; Han, Min−Koo; Tan, Yufang; Wu, Min; Zhang, Jun; Wu, Yiping; Zhang, Qi

doi:10.3389/fimmu.2022.830158

Cited by 10 publications

(14 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to eliminate the effect of heterogeneity, we included only signatures generated using the TCGA database. AUC was used to assess the predictive power of signatures, and a larger AUC indicates better classification ability ( Fawcett, 2006 ), and it could be used to compare the performance of the signatures ( Zhang et al, 2021 ; Lv et al, 2022 ). We integrated all the important information of the thirteen signatures, including author, year, gene signature and the AUCs of the signatures ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

Jia

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Breast cancer (BC) is the most diagnosed cancer in women. Cuproptosis is new regulated cell death, distinct from known death mechanisms and dependent on copper and mitochondrial respiration. However, the comprehensive relationship between cuproptosis and BC is still blank until now. In the present study, we acquired 13 cuproptosis-related regulators (CRRs) from the previous research and downloaded the RNA sequencing data of TCGA-BRCA from the UCSC XENA database. The 13 CRRs were all differently expressed between BC and normal samples. Using consensus clustering based on the five prognostic CRRs, BC patients were classified into two cuproptosis-clusters (C1 and C2). C2 had a significant survival advantage and higher immune infiltration levels than C1. According to the Cox and LASSO regression analyses, a novel cuproptosis-related prognostic signature was developed to predict the prognosis of BC effectively. The high- and low-risk groups were divided based on the risk scores. Kaplan-Meier survival analysis indicated that the high-risk group had shorter overall survival (OS) than the low-risk group in the training, test and entire cohorts. GSEA indicated that the immune-related pathways were significantly enriched in the low-risk group. According to the CIBERSORT and ESTIMATE analyses, patients in the high-risk group had higher infiltrating levels of antitumor lymphocyte cell subpopulations and higher immune score than the low-risk group. The typical immune checkpoints were all elevated in the high-risk group. Furthermore, the high-risk group showed a better immunotherapy response than the low-risk group based on the Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS). In conclusion, we identified two cuproptosis-clusters with different prognoses using consensus clustering in BC. We also developed a cuproptosis-related prognostic signature and nomogram, which could indicate the outcome, the tumor immune microenvironment, as well as the response to immunotherapy.

show abstract

Section: Resultsmentioning

confidence: 99%

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

Jia

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…In general, these reports highlight the underlying efficiency of glycosylation-based signature in predicting cancer prognosis. In our previous study, we successfully established a 9-gene signature under glycosylation characteristics for predicting BC prognosis, and BC patients with different outcomes obviously got different risk scores ( 15 ). Based on this, we further constructed an 8-GT-lncRNA signature.…”

Section: Discussionmentioning

confidence: 99%

“…harnessed 4 glycosylation-related mRNAs to calculate the risk score in ovarian cancer, and the risk score was negatively correlated with tumor purity and tumor mutation burden, which suggested that low-risk scores might predict a better benefit from ICI treatment ( 14 ). Our previous study screened 9 glycosyltransferase genes to develop a prognostic signature in BC, and the high-risk-group patients showed shorter survival probability and more immunosuppressive profile ( 15 ). However, there are no reports on establishing prognostic signature based on glycosylation-related long non-coding RNAs (lncRNAs) for predicting BC prognosis and response to ICI therapy.…”

Section: Introductionmentioning

confidence: 99%

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

Tan

Zhou

et al. 2022

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Aberrant glycosylation, a post-translational modification of proteins, is regarded to engage in tumorigenesis and malignant progression of breast cancer (BC). The altered expression of glycosyltransferases causes abnormal glycan biosynthesis changes, which can serve as diagnostic hallmarks in BC. This study attempts to establish a predictive signature based on glycosyltransferase-related lncRNAs (GT-lncRNAs) in BC prognosis and response to immune checkpoint inhibitors (ICIs) treatment. We firstly screened out characterized glycosyltransferase-related genes (GTGs) through NMF and WGCNA analysis and identified GT-lncRNAs through coexpression analysis. By using the coefficients of 8 GT-lncRNAs, a risk score was calculated and its median value divided BC patients into high-and low-risk groups. The analyses unraveled that patients in the high-risk group had shorter survival and the risk score was an independent predictor of BC prognosis. Besides, the predictive efficacy of our risk score was higher than other published models. Moreover, ESTIMATE analysis, immunophenoscore (IPS), and SubMAP analysis showed that the risk score could stratify patients with distinct immune infiltration, and patients in the high-risk group might benefit more from ICIs treatment. Finally, the vitro assay showed that MIR4435-2HG might promote the proliferation and migration of BC cells, facilitate the polarization of M1 into M2 macrophages, enhance the migration of macrophages and increase the PD-1/PD-L1/CTLA4 expression. Collectively, our well-constructed prognostic signature with GT-lncRNAs had the ability to identify two subtypes with different survival state and responses to immune therapy, which will provide reliable tools for predicting BC outcomes and making rational follow-up strategies.

show abstract

“…Among the eight key genes potentially targeted by the above three miRNAs identified in our study, STT3A, a catalytic subunit of the oligosaccharyltransferase, increases amyloid- β production by promoting N-glycosylation in the pathogenesis of Alzheimer's disease [ 50 ]. Besides, the expression level of STT3A was found to be negatively related to the biomarker expressions of M1 macrophages in breast cancer [ 51 ], indicating that STT3A may be involved in the regulating macrophage activation. Although the mechanism of regulating macrophages or mast cells has been extensively study, whether hsa-miR-15b-5p/hsa-miR-184/hsa-miR-16-5p-STT3A axis is involved in the regulating macrophages or mast activation in IS need further investigation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed microRNAs Associated with Ischemic Stroke by Integrated Bioinformatics Approaches

Jiang

Geng

et al. 2022

International Journal of Genomics

View full text Add to dashboard Cite

Ischemic stroke (IS) is one of the leading causes of disability and mortality worldwide. This study aims to find the crucial exosomal miRNAs associated with IS by using bioinformatics methods, reveal potential biomarkers for IS, and investigate the association between the identified biomarker and immune cell pattern in the peripheral blood of IS patients. In this study, 3 up-regulated miRNAs (hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p) miRNAs in the serum exosomes between IS patients and healthy controls from GEO database (GSE199942) and 25 down-regulated genes of peripheral blood mononuclear cells of IS patients from GSE22255 were obtained with the help of the R software. GO annotation and KEGG pathway enrichment analysis showed that the 25 down-regulated genes were associated with coenzyme metabolic process and were mainly enriched in the N-glycan biosynthesis pathway. Furthermore, we performed the LASSO algorithm to narrow down the above 25 intersected genes, and identified 8 key genes which had a good diagnostic value in discriminating IS patients from the healthy controls analyzed with ROC curve. CIBERSORT algorithm indicated that the abundance of M0 macrophages and resting mast cells was significantly lower than that of the control group. The spearman correlation analysis showed that STT3A was negatively correlated with the proportion of follicular helper T cells, activated NK cells and resting dendritic cells. Finally, GSE117064 showed that has-miR-16-5p was more advantageous for diagnosing stroke. In conclusion, hsa-miR-15b-5p, hsa-miR-184, and hsa-miR-16-5p are identified as specific related exosomal miRNAs for IS patients. These genes may provide new targets for the early identification of IS.

show abstract

Analysis of Tumor Glycosylation Characteristics and Implications for Immune Checkpoint Inhibitor’s Efficacy for Breast Cancer

Cited by 10 publications

References 47 publications

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

The cuproptosis-related signature predicts prognosis and indicates immune microenvironment in breast cancer

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

Identification of Differentially Expressed microRNAs Associated with Ischemic Stroke by Integrated Bioinformatics Approaches

Contact Info

Product

Resources

About