A single-cell characterised signature integrating heterogeneity and microenvironment of lung adenocarcinoma for prognostic stratification

EBioMedicine, Год журнала: 2024, Номер 102, С. 105092 - 105092

Опубликована: Март 28, 2024

The high heterogeneity of tumour and the complexity microenvironment (TME) greatly impacted development prognosis cancer in era immunotherapy. In this study, we aimed to portray single cell-characterised landscape lung adenocarcinoma (LUAD), develop an integrated signature incorporating both TME for stratification.

Язык: Английский

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Multi-omics identification of GPCR gene features in lung adenocarcinoma based on multiple machine learning combinations

Journal of Cancer, Год журнала: 2024, Номер 15(3), С. 776 - 795

Опубликована: Янв. 1, 2024

Background: Lung adenocarcinoma is a common malignant tumor that ranks second in the world and has high mortality rate.G protein-coupled receptors (GPCRs) have been reported to play an important role cancer; however, G receptor-associated features not adequately investigated.Methods: In this study, GPCR-related genes were screened at single-cell bulk transcriptome levels based on AUcell, single-sample gene set enrichment analysis (ssGSEA) weighted co-expression network (WGCNA) analysis.And new machine learning framework containing 10 algorithms their multiple combinations was used construct consensus receptor-related signature (GPCRRS).GPCRRS validated training external validation set.We constructed GPCRRS-integrated nomogram clinical prognosis prediction tools.Multi-omics analyses included genomics, transcriptomics, transcriptomics gain more comprehensive understanding of prognostic features.We assessed response risk subgroups immunotherapy for personalized drugs targeting specific subgroups.Finally, expression key GPCRRS verified by RT-qPCR.Results: we identified GPCR-associated significantly associated with lung transcriptome.Univariate multivariate showed survival rate higher low than risk, which also suggested model independent factor LUAD.In addition, observed significant differences biological function, mutational landscape, immune cell infiltration microenvironment between groups.Notably, relevant groups.In potential identified. Conclusion:In signature, predicting effect immunotherapy.It hypothesized LDHA, GPX3 DOCK4 are targets adenocarcinoma, can achieve breakthroughs prediction, targeted prevention treatment provide guidance anti-tumor.

Язык: Английский

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Integrated analysis of single-cell and bulk RNA-sequencing identifies a signature based on T-cell marker genes to predict prognosis and therapeutic response in lung squamous cell carcinoma

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Окт. 14, 2022

Cancer immunotherapy is an increasingly successful strategy for treating patients with advanced or conventionally drug-resistant cancers. T cells have been proved to play important roles in anti-tumor and tumor microenvironment shaping, while these not explained lung squamous cell carcinoma (LUSC). In this study, we first performed a comprehensive analysis of single-cell RNA sequencing (scRNA-seq) data from the gene expression omnibus (GEO) database identify 72 T-cell marker genes. Subsequently, constructed 5-gene prognostic signature training cohort based on genes cancer genome atlas (TCGA) database, which was further validated testing GEO cohort. The areas under receiver operating characteristic curve at 1-, 3-, 5-years were 0.614, 0.713 0.702 cohort, 0.669, 0.603 0.645 0.661, 0.628 0.590 respectively. Furthermore, created highly reliable nomogram facilitate clinical application. Gene set enrichment showed that immune-related pathways mainly enriched high-risk group. Tumor immune indicated group exhibited higher score, stromal infiltration levels. Moreover, checkpoints human leukocyte antigen family all overexpressed Drug sensitivity revealed low-risk sensitive 8 chemotherapeutic drugs 4 drugs. short, our study reveals novel genes, provides new target theoretical support LUSC patients.

Язык: Английский

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T cell-related prognostic risk model and tumor immune environment modulation in lung adenocarcinoma based on single-cell and bulk RNA sequencing

Computers in Biology and Medicine, Год журнала: 2022, Номер 152, С. 106460 - 106460

Опубликована: Дек. 21, 2022

T cells are present in all stages of tumor formation and play an important role the microenvironment. We aimed to explore expression profile cell marker genes, constructed a prognostic risk model based on these genes Lung adenocarcinoma (LUAD), investigated link between this immunotherapy response. obtained single-cell sequencing data LUAD from literature, screened out 6 tissue biopsy samples, including 32,108 patients with non-small lung cancer, identify LUAD. Combined TCGA database, T-cell gene was constructed, GEO database used for verification. also association Based scRNA-seq 1839 were identified, after which consisting 9 signatures prognosis combination dataset. This divided into high-risk low-risk groups overall survival. The multivariate analysis demonstrated that independent factor. Analysis immune profiles showed presented discriminative immune-cell infiltrations immune-suppressive states. Risk scores closely correlated Linoleic acid metabolism, intestinal network IgA production drug metabolism cytochrome P450. Our study proposed novel patients. survival as well treatment outcomes may be accurately predicted by model, make population different infiltration immunosuppression state.

Язык: Английский

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The role of PD-1/PD-L1 axis in idiopathic pulmonary fibrosis: Friend or foe?

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Дек. 5, 2022

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease with bleak prognosis. Mounting evidence suggests that IPF shares bio-molecular similarities cancer. Given the deep understanding of programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in cancer immunity and successful application immune checkpoint inhibitors (ICIs) cancer, recent studies have noticed role PD-1/PD-L1 axis IPF. However, conclusions are ambiguous, latent mechanisms remain unclear. In this review, we will summarize based on current murine models clinical studies. We found plays more predominant profibrotic than its immunomodulatory by interacting multiple types pathways. Most preclinical also indicated blockade could attenuate severity mice models. This review bring significant insights into identifying new therapeutic targets.

Язык: Английский

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Comprehensive molecular characterizations of stage I–III lung adenocarcinoma with tumor spread through air spaces

Frontiers in Genetics, Год журнала: 2023, Номер 14

Опубликована: Фев. 2, 2023

Purpose: The aim of this study is to investigate integrative genomic spectra stage I-III lung adenocarcinoma with tumor spread through air spaces (STAS). Methods: We retrospectively identified 442 surgically resected patients pathological in Shanghai Chest Hospital from January 2018 February 2021. Surgically tissues were used for next-generation sequencing (NGS) a panel 68 cancer-related genes profile comprehensive molecular characterizations. Results: A total cases analyzed, including 221 (50%) STAS-positive (SP) and STAS-negative (SN) patients. In total, 440 (99.6%) positive the overall mutational spectrum, higher EGFR, TP53, KRAS, ALK, SMAD4, ERBB2 (62%, 42%, 14%, 10%, 7%, respectively). Compared SN population, there was significantly lower EGFR alteration single-nucleotide variant (SNV) mutation spectrum (52.5% vs 69.7%, p < 0.001) TP53 SP population (49.8% 34.8%, = 0.002). L858R missense (19.5% 37.6%, exon 20 indel (1.8% 5.9%, 0.045) more frequent population. detection rate ALK fusion rearrangements than that (13.1% 2.3%, 0.001). analysis signaling pathways, no significant difference discovered between No 1-year disease-free survival observed study. Conclusion: Significant differences exist STAS

Язык: Английский

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The key role of the NUDT3 gene in lung adenocarcinoma progression and its association with the manganese ion metabolism family

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 29, 2025

Lung adenocarcinoma is one of the most common malignant tumors worldwide. Its complex molecular mechanisms and high tumor heterogeneity pose significant challenges for clinical treatment. The manganese ion metabolism family plays a crucial role in various biological processes, abnormal expression NUDT3 gene multiple cancers has drawn considerable attention. This study aims to systematically analyze characteristics lung its association with progression, integrating single-cell transcriptomic analysis experimental validation using cell lines. employed comprehensive set analytical approaches. Single-cell two normal four samples from GSE149655 dataset was performed Seurat package identify annotate distinct populations, focusing on epithelial macrophage subtypes. Non-negative matrix factorization (NMF) variation (GSVA) were applied assess functional enrichment profiles across 14 cancers. Quantitative PCR (qPCR) conducted evaluate relative mRNA A549 lines compared BEAS-2B bronchial GAPDH used as reference normalization, levels these analyzed confirm bioinformatics findings. found be significantly upregulated highly correlated mutation burden (TMB) (MEs). analyses demonstrated elevated cells, increasing cells associated advanced stages. Furthermore, qPCR confirmed upregulation consistent data. These results also highlighted differences cancers, including BLCA, BRCA, COAD, notable mutations enriched underscores critical progression potential therapeutic target. findings contribute understanding cancer biology provide foundation precision therapies targeting adenocarcinoma.

Язык: Английский

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Expression of PSMD14 in lung adenocarcinoma and its impact on immune cell infiltration and prognosis: a comprehensive analysis based on RNA and single-cell RNA sequencing

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 22, 2025

Lung adenocarcinoma (LUAD) is distinguished by intricate relationships between tumor advancement and the immune microenvironment. The function of PSMD14 (Proteasome 26S Subunit, Non-ATPase 14) within context LUAD not well elucidated, especially in terms its correlation with cell infiltration prognosis patients. objective this research was to explore expression levels evaluate potential implications for immunity clinical outcomes. A multifaceted approach adopted, which included analysis RNA sequencing (RNA-seq) data, assessment infiltration, survival analysis, gene enrichment integration single-cell RNA-seq data thoroughly biological relevance PSMD14. Furthermore, we examined parameters. Immunohistochemistry techniques were employed analyze samples invasive pulmonary adenocarcinoma. Our study demonstrated that markedly elevated exhibits a positive other members JAMM family, including EIF3H PSMD7. Importantly, linked poor patient prognosis, indicating utility as biomarker. Moreover, Kyoto Encyclopedia Genes Genomes (KEGG) pathway revealed significantly associated pathways related cycle nicotine dependence, underscoring vital modulating proliferation metabolic activities. found be cells, particularly influencing T helper Th2 populations, exhibited an inverse relationship several checkpoint molecules, such PD-1 TIGIT. Insights from identified PSMD14-expressing types include dendritic (DC), monocytes, tissue stem cells. These findings highlight role evasion strategies prevalent LUAD. Additionally, notable increase protein recorded patients, correlating size, lymph node involvement, TNM classification. In summary, our underscores crucial LUAD, highlighting promise target therapy prognostic indicator. it opens up novel approaches future therapeutic interventions.

Язык: Английский

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Construction of lung adenocarcinoma subtype and prognosis model based on fatty acid metabolism-related genes

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Май 22, 2025

To explore the role of genes related to fatty acid metabolism in lung adenocarcinoma classification and prognosis. Transcriptome clinical data from TCGA database GEO were collected, expression prognostic metabolism-related LUAD patients was analyzed, key both subtype identified. These further filtered via LASSO regression method, retained used construct a risk-scoring model. The biological function RPS4Y1 verified by cell viability, colony formation, migration, flow cytometry assays. Finally, immune infiltration drug sensitivity analyzed high- low-risk groups. 31 FAMGs associated with prognosis identified patients. cases divided into 3 subtypes on basis these genes. DEGs between different mainly amino metabolic pathways. In addition, among 46 subtypes, 5 (SCGB3 A2, PGC, ADH7, RPS4Y1, KRT6 A) as best markers establish risk scoring Patients low scores had better greater degree than those high scores. is highly expressed LUAD, its knockdown significantly inhibits growth tumor cells. Moreover, we also drugs likely be effective for play important roles may new targets treatment.

Язык: Английский

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Single-cell and bulk RNA sequencing identifies T cell marker genes score to predict the prognosis of pancreatic ductal adenocarcinoma

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Март 6, 2023

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies, with limited biomarkers identified to predict its prognosis and treatment response immune checkpoint blockade (ICB). This study aimed explore predictive ability T cell marker genes score (TMGS) their overall survival (OS) ICB by integrating single-cell RNA sequencing (scRNA- seq ) bulk RNA- data. Multi-omics data PDAC were applied in this study. The uniform manifold approximation projection (UMAP) was utilized for dimensionality reduction cluster identification. non-negative matrix factorization (NMF) algorithm molecular subtypes clustering. Least Absolute Shrinkage Selection Operator (LASSO)-Cox regression adopted TMGS construction. prognosis, biological characteristics, mutation profile, function status between different groups compared. Two via NMF: proliferative (C1) (C2). Distinct prognoses characteristics observed them. developed based on 10 (TMGs) through LASSO-Cox regression. an independent prognostic factor OS PDAC. Enrichment analysis indicated that cycle proliferation-related pathways are significantly enriched high-TMGS group. Besides, related more frequent KRAS , TP53 CDKN2A germline mutations than low-TMGS Furthermore, associated attenuated antitumor immunity reduced infiltration compared However, high correlated higher tumor burden (TMB), a low expression level inhibitory molecules, dysfunction score, thus having rate. On contrary, favorable rate chemotherapeutic agents targeted therapy. By combining scRNA- data, we novel biomarker, TMGS, which has remarkable performance predicting guiding pattern patients

Язык: Английский

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