Machine learning-based identification of tumor-infiltrating immune cell-associated lncRNAs for improving outcomes and immunotherapy responses in patients with low-grade glioma

Theranostics, Journal Year: 2022, Volume and Issue: 12(13), P. 5931 - 5948

Published: Jan. 1, 2022

Rationale: Accumulating evidence demonstrated that long noncoding RNAs (lncRNAs) involved in the regulation of immune system and displayed a cell-type-specific pattern cell subsets. Given vital role tumor-infiltrating lymphocytes effective immunotherapy, we explored cell-associated lncRNA (TIIClncRNA) low-grade glioma (LGG), which has never been uncovered yet. Methods: This study utilized novel computational framework 10 machine learning algorithms (101 combinations) to screen out TIIClncRNAs by integratively analyzing sequencing data purified cells, LGG lines, bulk tissues. Results: The established TIIClnc signature based on 16 most potent could predict outcomes public datasets Xiangya in-house dataset with decent efficiency showed better performance when compared 95 published signatures. was strongly correlated characteristics, including microsatellite instability, tumor mutation burden, interferon γ, exhibited more active immunologic process. Furthermore, predicted superior immunotherapy response multiple across cancer types. Notably, positive correlation between CD8, PD-1, PD-L1 verified dataset. Conclusions: enabled precise selection population who were potential beneficiaries immunotherapy.

Language: Английский

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Identification of a novel cuproptosis-related gene signature and integrative analyses in patients with lower-grade gliomas

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 15, 2022

Background Cuproptosis is a newly discovered unique non-apoptotic programmed cell death distinguished from known mechanisms like ferroptosis, pyroptosis, and necroptosis. However, the prognostic value of cuproptosis correlation between tumor microenvironment (TME) in lower-grade gliomas (LGGs) remain unknown. Methods In this study, we systematically investigated genetic transcriptional variation, value, expression patterns cuproptosis-related genes (CRGs). The CRG score was applied to quantify subtypes. We then evaluated their values TME, prediction, therapeutic responses LGG. Lastly, collected five paired LGG matched normal adjacent tissue samples Sun Yat-sen University Cancer Center (SYSUCC) verify signature by quantitative real-time PCR (qRT-PCR) Western blotting (WB). Results Two distinct clusters were identified using consensus unsupervised clustering analysis. multilayer alterations with clinical characteristics, prognosis, TME infiltration observed. Then, well-performed risk model (CRG score) developed predict patients’ which validated two external cohorts. classified patients into high- low-risk groups according found that group showed significantly higher survival possibilities than those high-risk ( P <0.001). A high implies scores, more significant infiltration, increased mutation burden. Meanwhile, correlated cancer stem index, chemoradiotherapy sensitivity–related immune checkpoint genes, chemotherapeutic sensitivity, indicating association CRGs treatment responses. Univariate multivariate Cox regression analyses revealed an independent predictor for patients. Subsequently, highly accurate predictive established facilitating application score, showing good ability calibration. Additionally, crucial further qRT-PCR WB. Conclusion Collectively, demonstrated comprehensive overview profiles novel therapy status prognosis. Our findings highlight potential implications CRGs, suggesting may be target

Language: Английский

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Machine learning-based tumor-infiltrating immune cell-associated lncRNAs for predicting prognosis and immunotherapy response in patients with glioblastoma

Briefings in Bioinformatics, Journal Year: 2022, Volume and Issue: 23(6)

Published: Aug. 24, 2022

Abstract Long noncoding ribonucleic acids (RNAs; lncRNAs) have been associated with cancer immunity regulation. However, the roles of immune cell-specific lncRNAs in glioblastoma (GBM) remain largely unknown. In this study, a novel computational framework was constructed to screen tumor-infiltrating cell-associated (TIIClnc) for developing TIIClnc signature by integratively analyzing transcriptome data purified cells, GBM cell lines and bulk tissues using six machine learning algorithms. As result, could distinguish survival outcomes patients across four independent datasets, including Xiangya in-house dataset, more importantly, showed superior performance than 95 previously established signatures gliomas. revealed be an indicator infiltration level cells predicted response immunotherapy. The positive correlation between CD8, PD-1 PD-L1 verified dataset. newly demonstrated predictive biomarker, enabled precise selection population who would benefit from immunotherapy should validated applied near future.

Language: Английский

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Real-time glioblastoma tumor microenvironment assessment by SpiderMass for improved patient management

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(4), P. 101482 - 101482

Published: March 28, 2024

Glioblastoma is a highly heterogeneous and infiltrative form of brain cancer associated with poor outcome limited therapeutic effectiveness. The extent the surgery related to survival. Reaching an accurate diagnosis prognosis assessment by time initial therefore paramount in management glioblastoma. To this end, we are studying performance SpiderMass, ambient ionization mass spectrometry technology that can be used vivo without invasiveness, coupled our recently established artificial intelligence pipeline. We demonstrate both stratify isocitrate dehydrogenase (IDH)-wild-type glioblastoma patients into molecular sub-groups achieve over 90% accuracy after cross-validation. Interestingly, developed method offers same for prognosis. In addition, testing potential immunoscoring strategy based on SpiderMass fingerprints, showing association between immune cell infiltration, predict patient outcome.

Language: Английский

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Large-Scale Single-Cell and Bulk Sequencing Analyses Reveal the Prognostic Value and Immune Aspects of CD147 in Pan-Cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 6, 2022

CD147 plays an important role in promoting tumor proliferation and inhibiting cancer cell apoptosis the microenvironment. However, mechanisms by which is involved tumorigenesis remains unclear. This study systematically analyzed prognostic value immune characteristics of 31 types. The expression levels mutant landscapes pan-cancer were explored. Kaplan-Meier (KM) analysis was applied to analyze CD147. microenvironment evaluated via TIMER 2.0 R package (immunedeconv). We also explored on cells stromal through Gene Set Variation Analysis single-cell sequencing analysis. co-expression macrophage markers CD68 CD163 detected using multiplex immunofluorescence staining tissue microarrays. found be overexpressed almost all types, related poor outcome. exhibited a strong association with infiltrates, checkpoint molecules, neoantigen In addition, expressed various types microenvironment, including cells, macrophages, T monocytes, fibroblasts, etc. Furthermore, revealed pattern many Finally, immunotherapy response sensitive small molecule drugs based predicted. sum, has significant relationship clinical outcome infiltrates multiple Inhibiting CD147-dependent signaling pathways might promising therapeutic strategy for immunotherapy.

Language: Английский

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Origin, activation, and targeted therapy of glioma-associated macrophages

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 6, 2022

The glioma tumor microenvironment plays a crucial role in the development, occurrence, and treatment of gliomas. Glioma-associated macrophages (GAMs) are most widely infiltrated immune cells (TME) one major cell populations that exert functions. GAMs typically originate from two types-brain-resident microglia (BRM) bone marrow-derived monocytes (BMDM), depending on variety cytokines for recruitment activation. mainly contain functionally morphologically distinct activation types- classically activated M1 (antitumor/immunostimulatory) alternatively M2 (protumor/immunosuppressive). have been shown to affect multiple biological functions gliomas, including promoting growth invasion, angiogenesis, energy metabolism, resistance. Both highly plastic can polarize or interconvert under various malignant conditions. As relationship between gliomas has become more apparent, long promising targets therapy, many studies demonstrated therapeutic potential this target. Here, we review origin how they regulate development response therapies, current strategies targeting GAMs.

Language: Английский

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PTX3 mediates the infiltration, migration, and inflammation‐resolving‐polarization of macrophages in glioblastoma

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 28(11), P. 1748 - 1766

Published: July 20, 2022

Abstract Introduction Pentraxin 3 (PTX3) is an essential regulator of the immune system. However, immune‐modulatory role PTX3 in tumor microenvironment glioma has not been elucidated. Methods The RNA seq samples were obtained from Cancer Genome Atlas (TCGA) and China Glioma (CGGA) datasets. single‐cell sequencing data glioblastoma (GBM) Single Cell Portal platform ( http://singlecell.broadinstitute.org ). Immunohistochemistry was used to assess expression, HAVCR2, PD‐1, PD‐L1, CD276 sections Xiangya cohort n = 60). Multiplex immunofluorescence staining PTX3, CD68, CD163 performed several solid cancer types, including GBM. HMC3 cocultured with U251 U87, transwell assay flow cytometry explore migration polarization activity HMC3. Results expression significantly increased predicts worse survival cohort. closely related CD276, HAVCR2 microenvironment. Additionally, involved tumorigenic immunogenic processes, especially macrophages based on various signaling pathways cellular communications critical transcription factors. Specifically, actively mediates macrophages' infiltration, migration, inflammation‐resolving‐polarization. could also predict immunotherapy response. Conclusion critically macrophage inflammation‐resolving‐polarization modulates immunosuppressive

Language: Английский

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Advantages and drawbacks of dexamethasone in glioblastoma multiforme

Critical Reviews in Oncology/Hematology, Journal Year: 2022, Volume and Issue: 172, P. 103625 - 103625

Published: Feb. 11, 2022

Language: Английский

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MiR-146a-5p deficiency in extracellular vesicles of glioma-associated macrophages promotes epithelial-mesenchymal transition through the NF-κB signaling pathway

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: June 30, 2023

Abstract Glioma-associated macrophages (GAMs) are pivotal chains in the tumor immune microenvironment (TIME). GAMs mostly display M2-like phenotypes with anti-inflammatory features related to malignancy and progression of cancers. Extracellular vesicles derived from immunosuppressive (M2-EVs), essential components TIME, greatly impact malignant behavior GBM cells. M1- or M2-EVs were isolated vitro, human cell invasion migration reinforced under M2-EV treatment. Signatures epithelial-mesenchymal transition (EMT) also enhanced by M2-EVs. Compared M1-EVs, miR-146a-5p, considered key factor TIME regulation, was deficient according miRNA-sequencing. When miR-146a-5p mimic added, EMT signatures invasive migratory abilities cells correspondingly weakened. Public databases predicted miRNA binding targets interleukin 1 receptor-associated kinase (IRAK1) necrosis 6 (TRAF6) screened as genes. Bimolecular fluorescent complementation coimmunoprecipitation confirmed interactions between TRAF6 IRAK1. The correlation IRAK1 evaluated immunofluorescence (IF)-stained clinical glioma samples. TRAF6-IRAK1 complex is switch brake that modulates IKK phosphorylation NF-κB pathway activation, well behaviors Furthermore, a homograft nude mouse model explored mice transplanted TRAF6/IRAK1-overexpressing had shorter survival times while overexpression TRAF6/IRAK1 knockdown lived longer. This work indicated GBM, deficiency enhances through disinhibition IKK-dependent signaling providing novel therapeutic strategy targeting GBM.

Language: Английский

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Novel ferroptosis gene biomarkers and immune infiltration profiles in diabetic kidney disease via bioinformatics

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(2)

Published: Jan. 10, 2024

Abstract Diabetic kidney disease (DKD) is the primary cause of end‐stage renal disease, exhibiting high disability and mortality rates. Ferroptosis vital for progression DKD, but exact mechanism remains unclear. This study aimed to explore potential ferroptosis‐related genes in DKD their relationship with immune identify new diagnostic biomarkers help treat diagnose DKD. GSE30122 GSE47185 were obtained from Gene Expression Omnibus database integrated into a merged dataset, followed by functional enrichment analysis. Then differentially expressed screened. Ferroptosis‐related differentially‐expressed identified, gene ontology Protein–protein interaction networks constructed hub The cell‐infiltrating state dataset was assessed using appropriate algorithms. Immune signature subtypes consensus clustering Hub expression validated qRT‐PCR immunohistochemistry. A total Eleven screened Six potentially diagnostically favorable identified. Significantly increased γδT cells, resting mast macrophages infiltration observed group. Additionally, two distinct subgroups significantly correlated infiltrated cells. upregulated HK‐2 cells following glucose treatment human tissues patients identified as diabetic further validation needed.

Language: Английский

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