The role of molecular subtypes and immune infiltration characteristics based on disulfidptosis-associated genes in lung adenocarcinoma

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: June 13, 2023

Lung adenocarcinoma (LUAD) is the most common type of lung cancer which accounts for about 40% all cancers. Early detection, risk stratification and treatment are important improving outcomes LUAD. Recent studies have found that abnormal accumulation cystine other disulfide occurs in cell under glucose starvation, induces stress increases content bond actin cytoskeleton, resulting death, defined as disulfidptosis. Because study disulfidptosis its infancy, role disease progression still unclear. In this study, we detected expression mutation genes LUAD using a public database. Clustering analysis based on gene was performed differential subtype were analyzed. 7 used to construct prognostic model, causes differences investigated by immune-infiltration analysis, immune checkpoint drug sensitivity analysis. qPCR verify key line (A549) normal bronchial epithelial (BEAS-2B). Since G6PD had highest factor cancer, further verified protein cells western blot, confirmed through colony formation experiment interference with able significantly inhibit proliferation ability cells. Our results provide evidence new ideas individualized precision therapy

Language: Английский

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Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

Aging, Journal Year: 2023, Volume and Issue: 15(10), P. 4159 - 4181

Published: May 12, 2023

Hepatocellular carcinoma (HCC) is a type of liver cancer that originates from cells. It one the most common types and leading cause cancer-related death worldwide. Early detection treatment can improve HCC prognosis. Therefore, it necessary to further markers risk stratification. PANoptosome cytoplasmic polymer protein complex regulates proinflammatory programmed cell pathway called "PANoptosis". The role PANoptosis in remains unclear. In this study, molecular changes related genes (PAN-RGs) were systematically evaluated. We characterized heterogeneity by using consensus clustering identify two distinct subtypes. subtypes showed different survival rate, biological function, chemotherapy drug sensitivity immune microenvironment. After identification PAN-RG differential expression (DEGs), prognostic model was established Cox regression analysis minimum absolute contraction selection operator (LASSO), its value verified analysis, Kaplan-Meier curve receiver operating characteristic (ROC) curve. Our own specimens also used validate significance possible clinical selected targets. Subsequently, we conducted preliminary discussion on reasons for influence prognosis through TME resistance TMB other studies. This study provides new idea individualized precise HCC.

Language: Английский

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Integrated bulk and single-cell transcriptomic analysis unveiled a novel cuproptosis-related lipid metabolism gene molecular pattern and a risk index for predicting prognosis and antitumor drug sensitivity in breast cancer

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

Published: March 14, 2025

Breast cancer is the second most prevalent malignant tumor worldwide and highly heterogeneous. Cuproptosis, a newly identified form of cell death, intimately connected to lipid metabolism. This study investigated breast heterogeneity through lens cuproptosis-related metabolism genes (CLMGs), with goal predicting patient prognosis, immunotherapy efficacy, sensitivity anticancer drugs. By utilizing transcriptomic data from The Cancer Genome Atlas (TCGA) for cancer, we 682 CLMGs applied nonnegative matrix factorization (NMF) method categorize patients into four distinct clusters: cluster 1, ''immune-cold stroma-poor''; 2, ''immune-infiltrated''; 3, ''stroma-rich''; 4, ''moderate infiltration''. We subsequently developed risk model based on that incorporates ACSL1, ATP2B4, ATP7B, ENPP6, HSPH1, PIP4K2C, SRD5A3, ULBP1. demonstrated excellent prognostic predictive performance in both internal (testing entire sets) external (GSE20685 Kaplan–Meier Plotter validation sets. High-risk presented lower expression levels immune checkpoint-related immunophenoscores (IPSs), whereas low-risk higher CD8+ T-cell infiltration IPSs. Furthermore, index was positively correlated stemness could predict also confirmed SRD5A3 expressed participated promoting proliferation migration cells. In conclusion, results this provide new insights strategies assessing prognosis implementing precision treatment CLMGs.

Language: Английский

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Single-cell transcriptomics reveals the multidimensional dynamic heterogeneity from primary to metastatic gastric cancer

iScience, Journal Year: 2025, Volume and Issue: 28(2), P. 111843 - 111843

Published: Jan. 21, 2025

Language: Английский

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Development and Experimental Validation of Machine Learning-Based Disulfidptosis-Related Ferroptosis Biomarkers in Inflammatory Bowel Disease

Genes, Journal Year: 2025, Volume and Issue: 16(5), P. 496 - 496

Published: April 27, 2025

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, defined by intestinal epithelial cell death. While ferroptosis and disulfidptosis have been linked to IBD pathogenesis, functional significance disulfidptosis-related genes (DRFGs) in this remains poorly characterized. This investigation sought pinpoint DRFGs as diagnostic indicators clarify their mechanistic contributions progression. Methods: Four datasets (GSE65114, GSE87473, GSE102133, GSE186582) from GEO database were integrated identify differentially expressed (DEGs) (|log2FC| > 0.585, adj. p < 0.05). A Pearson correlation analysis was used link genes, followed machine learning (LASSO RF) screen core DRFGs. The immune subtypes single-cell sequencing (GSE217695) results analyzed. DSS-induced colitis Mus musculus (C57BL/6) model for validation. Results: Transcriptomic profiling identified 521 DEGs, with 16 Nine hub showed potential (AUC: 0.71–0.91). Functional annotation demonstrated that IBD-associated regulate diverse pathways, network revealing synergy. PPI networks prioritized DUOX2, NCF2, ACSL4, GPX2, CBS, LPCAT3 central hubs. Two exhibited divergent DRFG expression. Single-cell mapping revealed epithelial/immune compartment specificity. murine confirmed differential expression patterns DRFGs, concordant between qRT-PCR RNA-seq, emphasizing pivotal regulatory roles progression translational application. Conclusions: mediate via multi-signal pathway regulation across types, demonstrating prognostic potential.

Language: Английский

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Novel application of the ferroptosis-related genes risk model associated with disulfidptosis in hepatocellular carcinoma prognosis and immune infiltration

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e16819 - e16819

Published: Feb. 2, 2024

Hepatocellular carcinoma (HCC) stands as the prevailing manifestation of primary liver cancer and continues to pose a formidable challenge human well-being longevity, owing its elevated incidence mortality rates. Nevertheless, quest for reliable predictive biomarkers HCC remains ongoing. Recent research has demonstrated close correlation between ferroptosis disulfidptosis, two cellular processes, prognosis, suggesting their potential factors HCC. In this study, we employed combination bioinformatics algorithms machine learning techniques, leveraging RNA sequencing data, mutation profiles, clinical data from samples in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Consortium (ICGC) databases, develop risk prognosis model based on genes associated with disulfidptosis. We conducted an unsupervised clustering analysis, calculating score (RS) predict using these genes. Clustering analysis revealed distinct clusters, each characterized by significantly different prognostic immune features. median RS stratified TCGA, GEO, ICGC cohorts into high-and low-risk groups. Importantly, emerged independent factor all three cohorts, high-risk group demonstrating poorer more active immunosuppressive microenvironment. Additionally, exhibited higher expression levels tumor burden (TMB), checkpoints (ICs), leukocyte antigen (HLA), heightened responsiveness immunotherapy. A stem cell infiltration similarity cells group. Furthermore, drug sensitivity highlighted significant differences response antitumor drugs summary, our model, constructed ferroptosis-related effectively predicts prognosis. These findings hold implications patient stratification decision-making, offering valuable theoretical insights field.

Language: Английский

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Characteristic of molecular subtype based on lysosome-associated genes reveals clinical prognosis and immune infiltration of gastric cancer

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: May 1, 2023

Background Lysosome are involved in nutrient sensing, cell signaling, death, immune responses and metabolism, which play an important role the initiation development of multiple tumors. However, biological function lysosome gastric cancer (GC) has not been revealed. Here, we aim to screen lysosome-associated genes established a corresponding prognostic risk signature for GC, then explore underlying mechanisms. Methods The (LYAGs) were obtained from MSigDB database. Differentially expressed (DE-LYAGs) GC acquired based on TCGA database GEO According expression profiles DE-LYAGs, divided patients into different subgroups explored tumor microenvironment (TME) landscape immunotherapy response LYAG subtypes using GSVA, ESTIMATE ssGSEA algorithms. Univariate Cox regression analysis, LASSO algorithm multivariate analysis adopted identify LYAGs establish model with GC. Kaplan-Meier ROC utilized evaluate performance model. Clinical specimens also used verify bioinformatics results by qRT-PCR assay. Results Thirteen DE-LYAGs distinguish three samples. Expression 13 predicted prognosis, tumor-related immunological abnormalities pathway dysregulation these subtypes. Furthermore, constructed DEG suggested that higher score related short OS rate. indicated had independent excellent ability predicting prognosis patients. Mechanistically, remarkable difference was observed infiltration, response, somatic mutation drug sensitivity. showed compared adjacent normal tissues, most screened significant abnormal expressions change trends consistent results. Conclusions We novel could be served as biomarker Our study might provide new insights individualized prognostication precision treatment

Language: Английский

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A Novel TGF-β-Related Signature for Predicting Prognosis, Tumor Microenvironment, and Therapeutic Response in Colorectal Cancer

Biochemical Genetics, Journal Year: 2023, Volume and Issue: 62(4), P. 2999 - 3029

Published: Dec. 7, 2023

Language: Английский

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Integrated single-cell sequencing, spatial transcriptome sequencing and bulk RNA sequencing highlights the molecular characteristics of parthanatos in gastric cancer

Aging, Journal Year: 2024, Volume and Issue: 16(6), P. 5471 - 5500

Published: March 18, 2024

Background: Parthanatos is a novel programmatic form of cell death based on DNA damage and PARP-1 dependency. Nevertheless, its specific role in the context gastric cancer (GC) remains uncertain. Methods: In this study, we integrated multi-omics algorithms to investigate molecular characteristics parthanatos GC. A series bioinformatics were utilized explore clinical heterogeneity GC further predict outcomes. Results: Firstly, conducted comprehensive analysis omics features various human tumors, including genomic mutations, transcriptome expression, prognostic relevance. We successfully identified 7 types within microenvironment: myeloid cell, epithelial T stromal proliferative B NK cell. When compared adjacent non-tumor tissues, single-cell sequencing results from tissues revealed elevated scores for pathway across multiple types. Spatial transcriptomics, first time, unveiled spatial distribution signaling. patients with different signals often exhibited distinct immune microenvironment metabolic reprogramming features, leading The integration signaling indicators enabled creation survival curves that accurately assess patients' times statuses. Conclusions: parthanatos' unicellular transcriptomics time. Our model can be used distinguish individual outcomes

Language: Английский

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Single-cell data revealed exhaustion of characteristic NK cell subpopulations and T cell subpopulations in hepatocellular carcinoma

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: April 5, 2024

Background: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape tumor immune infiltrating cells (TIICs) in microenvironment HCC is great significance to probe molecular mechanisms. Methods: Based on single-cell data HCC, cell was revealed from perspective TIICs. Special subpopulations were determined by expression levels marker genes. Differential analysis conducted. activity each subpopulation based highly expressed CTLA4+ T-cell affecting survival analysis. A regulatory network inference clustering also performed determine transcription factor networks T subpopulations. Results: 10 types identified NK showed high abundance tissues. Two present, FGFBP2+ cells, B3GNT7+ cells. Four LAG3+ RCAN3+ HPGDS+ Th2 exhaustive subpopulation. High contributed poor prognostic outcomes promoted progression. Finally, factors regulated NR3C1, STAT1, STAT3, which activated, present Conclusion: subsets exhibited functional exhaustion characteristics that probably inhibited function through dominated STAT3.

Language: Английский

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