Integrated multiomics machine learning and mediated Mendelian randomization investigate the molecular subtypes and prognosis lung squamous cell carcinoma DOI Open Access
Zhanghao Huang, Jing Li, You Zhou

и другие.

Translational Lung Cancer Research, Год журнала: 2023, Номер 0(0), С. 0 - 0

Опубликована: Янв. 1, 2023

Lung squamous cell carcinoma (LUSC) lacks specific early diagnostic markers. Given the critical role of 5'-Nucleotidase Ecto (NT5E) in immune evasion and therapy resistance cancer cells involvement Dual Specificity Phosphatase 4 (DUSP4) tumor proliferation through inhibition ERK signaling pathway, incorporating NT5E DUSP4 into consensus machine learning signature (CMLS) system this study holds significant potential for investigating diagnosis microenvironment LUSC. The objective was to explore prognostic targets Employing integrated algorithms enhances ability identify molecular subtypes key features from multiple perspectives. A combination 10 clustering multi-omics data LUSC patients, merged with algorithms, used analyze high-resolution subsets develop a CMLS. Mediated Mendelian randomization (MR) utilized mediations between metabolites associated Cluster 1 demonstrated elevated infiltration stromal components, indicating an immunosuppressive predominantly driven by tumor-associated macrophages or other inhibitory cells. In contrast, 2 displayed metabolism-driven phenotype improved prognosis. MR provided further insights causal relationships among CMLS, macrophages, Validation RAS-RAF-MEK-ERK pathway conjunction CMLS reinforced characteristics integration offers robust framework predicting prognosis, elucidating interactions metabolic reprogramming LUSC, identifying patient subgroups likely benefit immunotherapy.

Язык: Английский

Mechanisms and Strategies of Immunosenescence Effects on Non-Small Cell Lung Cancer (NSCLC) Treatment: A Comprehensive Analysis and Future Directions DOI
Huatao Zhou,

Zilong Zheng,

Chengming Fan

и другие.

Seminars in Cancer Biology, Год журнала: 2025, Номер 109, С. 44 - 66

Опубликована: Янв. 9, 2025

Язык: Английский

Процитировано

3

Unlocking the potential of T‐cell metabolism reprogramming: Advancing single‐cell approaches for precision immunotherapy in tumour immunity DOI Creative Commons
Lihaoyun Huang, Haitao Li, Cangang Zhang

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(3)

Опубликована: Март 1, 2024

Abstract As single‐cell RNA sequencing enables the detailed clustering of T‐cell subpopulations and facilitates analysis metabolic states metabolite dynamics, it has gained prominence as preferred tool for understanding heterogeneous cellular metabolism. Furthermore, synergistic or inhibitory effects various pathways within T cells in tumour microenvironment are coordinated, increased activity specific generally corresponds to functional activity, leading diverse behaviours related immune cells, which shows potential tumour‐specific induce persistent responses. A holistic how heterogeneity governs function subsets is key obtaining field‐level insights into immunometabolism. Therefore, exploring mechanisms underlying interplay between metabolism functions will pave way precise immunotherapy approaches future, empower us explore new methods combating tumours with enhanced efficacy.

Язык: Английский

Процитировано

7

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer DOI Creative Commons
Jian-Rong Sun,

Chenfan Kong,

Yi-Xiang Ye

и другие.

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Апрель 1, 2024

Abstract Natural killer (NK) cells play essential roles in the tumor development, diagnosis, and prognosis of tumors. In this study, we aimed to establish a reliable signature based on marker genes NK cells, thus providing new perspective for assessing immunotherapy patients with gastric cancer (GC). We analyzed total 1560 samples retrieved from public database. performed comprehensive analysis single-cell RNA-sequencing (scRNA-seq) data identified 377 cells. By performing Cox regression analysis, established 12-gene cell-associated (NKCAS) Cancer Genome Atlas (TCGA) cohort, that assigned GC into low-risk group (LRG) or high-risk (HRG). TCGA areas under curve (AUC) value were 0.73, 0.81, 0.80 at 1, 3, 5 years. External validation predictive ability was then validated Gene Expression Omnibus (GEO) cohorts (GSE84437). The expression levels measured cell lines by real-time PCR. Moreover, NKCAS as an independent prognostic factor multivariate analysis. combined variety clinicopathological characteristics (age, M stage, grade) construct nomogram predict survival outcomes patients. LRG showed higher immune infiltration, especially CD8+ T risk score negatively associated inflammatory activities. Importantly, cohort had better response when compared HRG. identification study suggests potential therapeutic targets. Additionally, developed signatures nomograms may aid clinical management GC.

Язык: Английский

Процитировано

5

Heterogeneity analysis and prognostic model construction of HPV negative oral squamous cell carcinoma T cells using ScRNA-seq and bulk-RNA analysis DOI Creative Commons
Chunyan Li,

Zengbo Lv,

Chongxin Li

и другие.

Functional & Integrative Genomics, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 23, 2025

T cells are involved in every stage of tumor development and significantly influence the microenvironment (TME). Our objective was to assess T-cell marker gene expression profiles, develop a predictive risk model for human papilloma virus (HPV)-negative oral squamous cell carcinoma (OSCC) utilizing these genes, examine correlation between score immunotherapy response. We acquired scRNA-seq data HPV-negative OSCC from GEO datasets. performed cell‒cell communication, trajectory, pathway enrichment analyses T-cell-associated genes. In addition, we constructed validated prognostic patients using TCGA assessed immune infiltration status .qRT-PCR used detect level prognosis-related genes different groups. ScRNA-seq conducted on 28,000 derived 14 samples 6 normal samples. identified 4,635 774 differentially expressed genes(DEGs) associated with across five distinct subtypes. Through integration bulk-RNAseq data, established based DEGs related cells. By separating into high-risk low-risk groups according can accurately predict their survival rates TME.qRT-PCR results showed that compared low group, PMEPA1, SH2D2A, SMS PRDX4 were up-regulated high group. This study provides resource understanding heterogeneity models. It new insights predicting OSCC.

Язык: Английский

Процитировано

0

Identification and validation of a novel signature based on immune‑related genes from epithelial cells to predict prognosis and treatment response in patients with lung squamous cell cancer by integrated analysis of single‑cell and bulk RNA sequencing DOI Open Access
Jiajun Wu, Zhifeng Li, Weijun Zhou

и другие.

Oncology Letters, Год журнала: 2025, Номер 29(3)

Опубликована: Янв. 23, 2025

Epithelial cells are associated with tumor immunity through interstitial transformation, yet the role of epithelial immune‑related genes (EIGs) in this process remains unclear. Comprehending mechanisms behind EIGs within lung squamous cell carcinoma (LUSC) may offer an explanation to these issues. The present study aimed explore biological patients LUSC. Based on data from Gene Expression Omnibus and Cancer Genome Atlas databases, a survival model nomogram was established. This were used mechanism LUSC its medical significance by enrichment analysis, microenvironment, immune infiltration function correlation analysis. Finally, reverse transcription‑quantitative PCR (RT‑qPCR) external dataset assess expression EIGs. develop 4 as predictors for patient outcomes. Survival curves revealed that higher risk had more negative developed based entirely accurate prognosis predictive analysis indicated pathways related antigen processing presentation, well Epstein‑Barr virus infection, prevalent high‑risk populations. research demonstrated notable rise activated dendritic neutrophils group. Furthermore, results populations particularly susceptible effects afureserpine, gefitinib savolitinib. outcomes RT‑qPCR consistent those bioinformatics In conclusion, evaluation effective forecasting guiding drug selection A worse high be certain viral infections presentation.

Язык: Английский

Процитировано

0

Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells DOI Creative Commons
Peian Cai,

Haibo Sun,

Tongmeng Jiang

и другие.

Cancer Immunology Immunotherapy, Год журнала: 2025, Номер 74(4)

Опубликована: Фев. 25, 2025

Abstract Revealing the immunosenescence, particularly in CD4+ T cell function lung squamous carcinoma (LUSC) assists devising individual treatment strategies. This study identifies differentially expressed genes (DEGs) between ROS1 mutated ( MUT ) and wild-type WT LUSC samples from TCGA database. Using WGCNA, immune-related DEGs (IRGs) were screened. Prognostic signatures derived IRGs used to compare immune infiltration, chemotherapy sensitivity, immune-phenotyping score (IPS) high- low-risk subgroups. Hub gene abundance different clusters was analyzed via Sc-seq. TAGAP overexpression or silencing employed assess its impact on cytokines production differentiation of cells, downstream c-Rel expression, tumor progression. High-risk subgroups exhibited decreased infiltration natural killer, follicular helper T, CD8+ but increased plasma, memory resting macrophage M2 cells. These more sensitive Sunitinib CTLA4 blockade. expression significantly reduced LUSC. Overexpressing enhanced cells produce cytokines, promoted into Th1/Th17 inhibited Treg conversion, suppressed phenotype vitro. also growth boosted vivo. TAGAP’s effects partly reversed by overexpression, highlighting TAGAP's role rejuvenating exerting anticancer inhibiting c-Rel. elucidates novel therapeutic potential targeting modulate activity immunotherapy for

Язык: Английский

Процитировано

0

Single cell transcriptomic analysis reveals tumor immune infiltration by macrophage cells gene signature in lung adenocarcinoma DOI Creative Commons

Xiaotong Guo,

Youjun Deng, Wenjun Jiang

и другие.

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

Опубликована: Март 3, 2025

Tumor-associated macrophages (TAMs) play pivotal roles in innate immunity and contribute to the advancement of lung cancer. We aimed identify novel TAM-related biomarkers significance macrophage infiltration adenocarcinoma (LUAD) through an integrative analysis single-cell RNA-sequencing (scRNA-seq) data. To describe cell atlas construct a prognostic signature LUAD. The gene linked TAMs was identified utilizing Scanpy from scRNA-seq dataset GSE131907. Subsequent involved evaluating expression levels these genes, their potential molecular mechanisms, LUAD using data Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. also constructed risk score models LASSO Cox regression for genes. underlying mechanism further elucidated application GSEA, ESTIMATE, TIDE, other bioinformatic algorithms. Single-cell described by analyze 29 samples 19 patients. TAMs-related (TGS) as independent factor differential genes (DEGs) derived pro- anti-inflammatory cells. Risk model including nine (FOSL1, ZNF697, ADM, UBE2S, TICAM1, S100P, BIRC3, TLE1, DEFB1) were obtained prognosis construction. Moreover, underwent additional validation four external GEO cohorts: GSE31210, GSE72094, GSE26939, GSE30219. Interestingly, TGS-high tumors revealed enrichments TGF-β signaling hypoxia pathways, which shown low immune immunosuppression ESTIMATE TIDE algorithm. group exhibited lower richness diversity T-cell receptor (TCR) repertoire. This study introduces TGS developed analysis, DEGs High enrichment suggesting utility predicting responses patients with These results offer promising implications development therapeutic strategies

Язык: Английский

Процитировано

0

A Pan-Cancer Comparative Analysis of The Cancer Genome Atlas Transcriptomic TIL-Immune Signatures DOI

Kyle Hitscherich,

Darryl Noussome,

Aaron Dinerman

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Efforts to understand the tumor microenvironment (TME) through basic science research and The Cancer Genome Atlas (TCGA) data analysis have led creation of unique immune transcriptomic signatures from tumor-infiltrating lymphocytes (TIL). However, no pan-cancer has been conducted compare prognostic performance these using overall survival (OS) or progression-free interval (PFI) as endpoints. We compiled a library 146 TIL-immune evaluated gene signature score correlation with OS PFI for 9,961 available TCGA samples across 33 cancer types. Zhang CD8 TCS demonstrated higher accuracy in prognosticating both landscape, however, variability was seen types germ cell origin. Cluster group six (Oh.Cd8.MAIT, Grog.8KLRB1, Oh.TIL_CD4.GZMK, Grog.CD4.TCF7, Oh.CD8.RPL, Grog.CD4.RPL32) whose association could potentially be conserved multiple

Язык: Английский

Процитировано

0

Transcriptome-Based Traits of Radioresistant Sublines of Non-Small Cell Lung Cancer Cells DOI Open Access
Маргарита Пустовалова, Philipp Malakhov, Anastasia Guryanova

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 3042 - 3042

Опубликована: Фев. 3, 2023

Radioresistance is a major obstacle for the successful therapy of many cancers, including non-small cell lung cancer (NSCLC). To elucidate mechanism radioresistance NSCLC cells and to identify key molecules conferring radioresistance, radioresistant subclones p53 wild-type A549 p53-deficient H1299 cultures were established. The transcriptional changes between parental investigated by RNA-seq. In total, expression levels 36,596 genes measured. Changes in activation intracellular molecular pathways surviving irradiation relative quantified using Oncobox bioinformatics platform. Following 30 rounds 2 Gy irradiation, total 322 differentially expressed A549IR cells. For (H1299) cells, irradiated populations differed 1628 1616 pathways. associated with reflects complex biological processes involved clinical eradication might serve as potential biomarker therapeutic target treatment.

Язык: Английский

Процитировано

7

PCM1: A Potential Prognostic Biomarker Correlated with Immune Infiltration in Lung Adenocarcinoma DOI
Zhihua Guo,

Jinghao Liang,

Xin Zhang

и другие.

Current Proteomics, Год журнала: 2023, Номер 20(3), С. 208 - 221

Опубликована: Июнь 1, 2023

Background: Recent studies have validated the role of Pericentriolar Material 1 (PCM1) in several malignant tumour cell lines, but its specific biological function lung adenocarcinoma (LUAD) remains unclear. Objective: To address this gap, study analyzed 411 LUAD and control samples to evaluate prognostic value PCM1 using Cox regression analysis. Methods: Multiple genes co-expressed with were also investigate processes roles involved PCM1. An endogenous competitive network as key gene was constructed uncover regulatory relationships LUAD. The further explored immunological characteristics different expression groups based on immune infiltration Results: These findings indicated that higher levels associated better survival prognoses, possibly due antagonistic effects RHOC. Immunological analysis revealed a significant correlation between various levels, including CD4+ T cells, naïve B M2 macrophages, mast cells. However, there no relationship MSI, TMB, or stemness, although it positively correlated m6A genes. Patients lower responded CTLA-4 therapy. estimated some chemotherapeutic targeted agents might be effective treating patients high levels. mainly expressed cytoplasmic membranous structures. Conclusion: shows potential biomarker for strong ability enhance anticancer treatment sensitivity.

Язык: Английский

Процитировано

6