Dissecting macrophage heterogeneity and kaempferol in lung adenocarcinoma: a single-cell transcriptomic approach and network pharmacology DOI Creative Commons

Laiyi Wan,

Wentao Hao,

Leilei Li

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 30, 2025

Lung adenocarcinoma (LUAD) is a leading form of non-small cell lung cancer characterized by complex tumor microenvironment (TME) that influences disease progression and therapeutic response. Tumor-associated macrophages (TAMs) within the TME promote tumorigenesis evasion immune surveillance, though their heterogeneity poses challenges in understanding roles targeting. Additionally, traditional Chinese medicine (TCM) offers potential anti-cancer agents could modulate landscape. We conducted single-cell RNA sequencing (scRNA-seq) on LUAD samples, performing an in-depth analysis macrophage populations expression signatures. Network pharmacology was used to identify TCM components with TAM-modulatory effects, focusing Astragalus membranaceus. Pseudotime trajectory analysis, immunofluorescence staining, vitro assays examined functional TAMs effects selected compounds polarization. Our scRNA-seq identified notable among macrophages, revealing predominant M2-like phenotypes TAMs. highlighted active ingredients, including quercetin, isorhamnetin, kaempferol, targeting genes related function. Survival implicated AHSA1, CYP1B1, SPP1, STAT1 as prognostically significant factors. Further experiments demonstrated kaempferol's efficacy inhibiting M2 polarization, underlining selective influence TAM functionality. This study delineates diverse landscape suggests pivotal role for TAM-mediated immunosuppression. Kaempferol, from TCM, emerges influential agent capable altering potentially enhancing anti-tumoral immunity. These findings underscore translational integrating TCM-derived into immunotherapeutic strategies LUAD.

Language: Английский

An artificial intelligence network‐guided signature for predicting outcome and immunotherapy response in lung adenocarcinoma patients based on 26 machine learning algorithms DOI Creative Commons
Nan Zhang, Hao Zhang,

Zaoqu Liu

et al.

Cell Proliferation, Journal Year: 2023, Volume and Issue: 56(4)

Published: Feb. 23, 2023

Abstract The immune cells play an increasingly vital role in influencing the proliferation, progression, and metastasis of lung adenocarcinoma (LUAD) cells. However, potential cells' specific genes‐based model remains largely unknown. In current study, by analysing single‐cell RNA sequencing (scRNA‐seq) data bulk data, tumour‐infiltrating cell (TIIC) associated signature was developed based on a total 26 machine learning (ML) algorithms. As result, TIIC score could predict survival outcomes LUAD patients across five independent datasets. showed superior performance to 168 previously established signatures LUAD. Moreover, immunofluorescence staining tissue array prognostic value. Our research revealed solid connection between tumour immunity as well metabolism. Additionally, it has been discovered that can forecast genomic change, chemotherapeutic drug susceptibility, and—most significantly—immunotherapeutic response. newly demonstrated biomarker, facilitated selection population who would benefit from future clinical stratification.

Language: Английский

Citations

35
Mechanisms of cuproptosis and its relevance to distinct diseases DOI

Qiao-mei Lou,

Feifan Lai,

Jingwei Li

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(7-8), P. 981 - 1006

Published: June 2, 2024

Language: Английский

Citations

12
Habitat Imaging With Tumoral and Peritumoral Radiomics for Prediction of Lung Adenocarcinoma Invasiveness on Preoperative Chest CT: A Multicenter Study DOI
Youlan Shang, Ying Zeng,

Shiwei Luo

et al.

American Journal of Roentgenology, Journal Year: 2024, Volume and Issue: 223(4)

Published: Aug. 14, 2024

Tumor growth processes result in spatial heterogeneity, with the development of tumor subregions (i.e., habitats) having unique biologic characteristics.

Language: Английский

Citations

12
Identification of prognostic molecular subtypes and model based on CD8+ T cells for lung adenocarcinoma DOI Open Access

HONGMIN CAO,

Ying Xue, Fei Wang

et al.

Biocell, Journal Year: 2024, Volume and Issue: 48(3), P. 473 - 490

Published: Jan. 1, 2024

Background: Cytotoxic T lymphocytes (CD8+ T) cells function critically in mediating anti-tumor immune response cancer patients.Characterizing the specific functions of CD8+ lung adenocarcinoma (LUAD) could help better understand local responses and estimate effect immunotherapy.Methods: Gens related to were identified by cluster analysis based on single-cell sequencing data three LUAD tissues their paired normal tissues.Weighted gene co-expression network (WGCNA), consensus clustering, differential expression analysis, least absolute shrinkage selection operator (LASSO) Cox regression conducted classify molecular subtypes for develop a risk model using prognostic genes cells.Expression model, effects tumor cell invasion, interactions with verified experiments.Results: This study defined two clusters 0 1) cells, being significantly associated prognosis LUAD.Three heterogeneous (clusters 1, 2, 3) differing prognosis, genome mutation events, status categorized 42 genes.A created 11 significant (including CD200R1, CLEC17A, ZC3H12D, GNG7, SNX30, CDCP1, NEIL3, IGF2BP1, RHOV, ABCC2, KRT81) was able independently death patients different cohorts.Moreover, also showed general applicability external validation cohorts.Low-risk benefit more from taking immunotherapy resistance anticancer drugs.The results experiments demonstrated that SNX30 downregulated, while ABCC2 KRT81 upregulated cells.Inhibition CD200R1 greatly increased invasiveness but inhibiting CDCP1 weakened invasion ability cells.Conclusion: classified LUAD.A predictive potential developed.

Language: Английский

Citations

10
Joint multi-omics screening of neutrophil-related biomarkers for lung adenocarcinoma DOI Creative Commons
Yunfeng Li,

Jie Fei,

Hongyan Yu

et al.

ONCOLOGIE, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

Citations

1
CCL20 promotes lung adenocarcinoma progression by driving epithelial-mesenchymal transition DOI Creative Commons
Tao Fan, Shuofeng Li, Xiao Chu

et al.

International Journal of Biological Sciences, Journal Year: 2022, Volume and Issue: 18(11), P. 4275 - 4288

Published: Jan. 1, 2022

C-C motif chemokine ligand 20 (CCL20) participates in multiple oncogenic processes, but its role lung adenocarcinoma (LUAD) is unclear.Herein, we explored the mechanism by which CCL20 works LUAD progression.We performed bioinformatical analyses based on complete transcriptome sequencing data from 1544 cases 4 independent cohorts to evaluate signaling pathways regulated CCL20.We established A549 and H358 cell lines with knockdown explore how promotes tumor progression vitro vivo experiments.Using another cohort of 348 urothelial carcinoma patients treated anti-PD-L1 agent (atezolizumab), synergistic effect TGF-β immunotherapy efficacy.High expression a poor prognostic marker for patients, associated enhanced epithelial-mesenchymal transition (EMT), inflammatory response, activated TNF pathway LUAD.CCL20 restrained EMT process proliferation cells vivo.Low blocked detrimental effects high survival effectively improved patients' response therapy.Collectively, revealed underlying mechanisms largest sample size.The inhibitory immune-checkpoint blockade therapy efficacy provides new views resistance.

Language: Английский

Citations

29
Circular RNA circATP9A promotes non-small cell lung cancer progression by interacting with HuR and by promoting extracellular vesicles-mediated macrophage M2 polarization DOI Creative Commons
Yuanshan Yao, Chunji Chen, Jing Wang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Dec. 5, 2023

Abstract Background CircRNA is recognized for its significant regulatory function across various cancers. However, role in non-small cell lung cancer (NSCLC) still largely uncharted. Methods Analysis based on public databases completed using R software. circATP9A was identified by two circRNA datasets of NSCLC from the Gene Expression Omnibus database. To examine impact phenotype NSCLC, we conducted both vitro and vivo functional experiments. The mRNA protein levels specific molecules were determined through quantitative real-time PCR western blot assays. RNA pulldown immunoprecipitation assays performed to verify interaction between protein. extracellular vesicles (EVs)-circATP9A tumor-associated macrophage (TAM) polarization assessed co-culture system flow cytometry. Results Here, elucidates NSCLC. We demonstrated that can foster progression From a mechanistic standpoint, interact with HuR form an RNA–protein complex, subsequently amplifying target gene NUCKS1. Further, PI3K/AKT/mTOR signaling as downstream pathways circATP9A/HuR/NUCKS1 axis. More notably, hnRNPA2B1 mediate incorporation into EVs. Subsequently, these EVs containing induce M2 TAMs, thereby facilitating development. Conclusions Our discoveries indicate could serve promising diagnostic indicator therapeutic

Language: Английский

Citations

17
Deciphering lung adenocarcinoma prognosis and immunotherapy response through an AI‐driven stemness‐related gene signature DOI Creative Commons

Bicheng Ye,

Ge Hongting,

Wen Zhuang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(14)

Published: July 1, 2024

Lung adenocarcinoma (LUAD) is a leading cause of cancer-related deaths, and improving prognostic accuracy vital for personalised treatment approaches, especially in the context immunotherapy. In this study, we constructed an artificial intelligence (AI)-driven stemness-related gene signature (SRS) that deciphered LUAD prognosis immunotherapy response. CytoTRACE analysis single-cell RNA sequencing data identified genes associated with stemness epithelial cells. An AI network integrating traditional regression, machine learning, deep learning algorithms SRS based on stemness. Subsequently, conducted comprehensive exploration connection between both intrinsic extrinsic immune environments using multi-omics data. Experimental validation through siRNA knockdown cell lines, followed by assessments proliferation, migration, invasion, confirmed functional role CKS1B, top gene. The demonstrated high precision predicting likelihood benefiting from High-risk groups classified exhibited decreased immunogenicity reduced infiltration, indicating challenges Conversely, vitro experiments revealed CKS1B significantly impaired aggressive cancer phenotypes like invasion cells, highlighting its pivotal role. These results underscore close association tumour immunity, offering predictive insights into landscape responses LUAD. newly established holds promise as valuable tool selecting populations likely to benefit future clinical stratification efforts.

Language: Английский

Citations

8
Preparation and mechanism analysis of non-contact respiratory sensor based on ZnO/RGO composites DOI
Hongyan Zhang,

Weiyuan Gu,

Chu Chen

et al.

Applied Surface Science, Journal Year: 2022, Volume and Issue: 599, P. 154031 - 154031

Published: June 27, 2022

Language: Английский

Citations

23
New strategies for lung cancer diagnosis and treatment: applications and advances in nanotechnology DOI Creative Commons
Jiaqi Feng,

Pengpeng Zhang,

Dingli Wang

et al.

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Nov. 13, 2024

Lung cancer leads in causing cancer-related mortality worldwide, continually posing a significant threat to human health. Current imaging diagnostic techniques, while offering non-invasive detection, suffer from issues such as insufficient sensitivity and the risks associated with radiation exposure. Pathological diagnosis, gold standard for confirmation, also faces challenges like invasiveness high costs. In treatment, surgery, radiotherapy, chemotherapy are main modalities, each encountering related precision, environmental adaptability, side effects. Nanotechnology's advancement provides new solutions diagnosis treatment of lung cancer, promising enhance accuracy reduce effects during treatment. This article introduces types nanomaterials used field comprehensive overview current research on application nanotechnology early screening, monitoring summarizing ongoing clinical findings.

Language: Английский

Citations

6