Training and experimental validation a novel anoikis- and epithelial‒mesenchymal transition-related signature for evaluating prognosis and predicting immunotherapy efficacy in gastric cancer

Journal of Cancer, Journal Year: 2025, Volume and Issue: 16(4), P. 1078 - 1100

Published: Jan. 6, 2025

Anoikis resistance and improper activation of epithelial‒mesenchymal transition (EMT) are critical factors in tumor metastasis progression. Despite their interaction, the combined impact anoikis EMT on prognosis immunotherapy gastric cancer remains underexplored. In this study, we identified 354 anoikis- EMT-related genes (AERGs) through Venn analysis performed unsupervised clustering to classify patients into two molecular clusters: A B. Molecular cluster showed poor an immunosuppressive microenvironment, suggesting a "cold tumor" phenotype. Then, novel AERG-related prognostic model comprising CD24, CRYAB, MMP11, MUC4, PRKAA2, SERPINE1, SKP2, TP53 was constructed validated, accurately predicting 1-, 3-, 5-year survival rates patients. Multivariate revealed that risk score independent factor (hazard ratio = 1.651, 95% confidence interval 1.429-1.907, P<0.001). Further studies demonstrated that, compared high-risk group, low-risk group exhibited higher CD8+ T cell infiltration, mutational burden, immunophenoscores, lower immune dysfunction exclusion scores, indicating potential sensitivity immunotherapy. RT‒qPCR immunohistochemical staining validated expression levels model's markers. Overall, our shows promise for outcomes guiding selection tailored precise therapies

Language: Английский

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AC129507.1 is a ferroptosis-related target identified by a novel mitochondria-related lncRNA signature that is involved in the tumor immune microenvironment in gastric cancer

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 6, 2025

Gastric cancer (GC) is one of the most common malignancies. Previous studies have shown that mitochondrial metabolism associated with However, relevant research on mitochondria-related lncRNAs in GC lacking. We integrated corresponding information patients from The Cancer Genome Atlas (TCGA) database. Mitochondria-related were selected based differential expression and a correlation analysis to construct prognostic model. mutation data analyzed distinguish differences tumor burden (TMB). Single-sample gene set enrichment (ssGSEA) was performed evaluate immunological differences. A series cell-based experiments adopted biological behavior GC. total 1571 identified. signature incorporating nine built 293 suitable cases could predict patient prognosis. TMB ssGSEA indicated low-risk group displayed increased immune function. differentially expressed genes enriched metabolic functions. AC129507.1 significantly upregulated cells poor prognosis, its knockdown inhibited proliferation migration cells. Mechanistically, silencing led abnormal glycolipid oxidative stress, thus inducing ferroptosis. Our nine-lncRNA risk powerfully promoted malignant phenotypes play nonnegligible role by promoting formation immunosuppressive microenvironment inhibiting initiation ferroptosis, which needs be further explored.

Language: Английский

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Non-coding RNAs participate in interactions between senescence and gastrointestinal cancers

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 3, 2025

Relationships between cellular senescence and gastrointestinal cancers have gained prominence in recent years. The currently accepted theory suggests that cancer occurrence exhibit "double-edged sword" effects. Cellular is related to via four "meta-hallmarks" i.e., genomic instability, epigenetic alterations, chronic inflammation, dysbiosis, along with two "antagonistic hallmarks" telomere attrition stem cell exhaustion. These relationships are characterized by both agonistic antagonistic elements, but the existence of an intricate dynamic balance remains unknown. Non-coding RNAs (ncRNAs) vital roles post-transcriptional regulation, how they participate be fully investigated. In this article, we systematically review ncRNAs (including microRNAs (miRNAs), long (lncRNAs), circularRNAs (circRNAs)) interactions cancers. Our aim elucidate a triangular relationship "ncRNAs-senescence-gastrointestinal cancers" which considered these three elements as equal important standing. We keen identify prognostic or therapeutic targets for from, aging-related ncRNAs, discover novel strategies treat manage elderly. seek clarify complex where "senescence-gastrointestinal interactions.

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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Molecular Signatures of Cellular Senescence in Cancer: A Critical Review of Prognostic Implications and Therapeutic Opportunities

Mechanisms of Ageing and Development, Journal Year: 2025, Volume and Issue: unknown, P. 112052 - 112052

Published: March 1, 2025

Language: Английский

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High expression of SRSF1 facilitates osteosarcoma progression and unveils its potential mechanisms

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: May 12, 2024

Abstract Background SRSF1, a member of Serine/Arginine-Rich Splicing Factors (SRSFs), has been observed to significantly influence cancer progression. However, the precise role SRSF1 in osteosarcoma (OS) remains unclear. This study aims investigate functions and its underlying mechanism OS. Methods expression level OS was evaluated on TCGA dataset, TAGET-OS database. qRT-PCR Western blotting were employed assess human cell lines as well interfered ectopic states. The effect migration, invasion, proliferation, apoptosis cells measured by transwell assay flow cytometry. RNA sequence bioinformatic analyses conducted elucidate targeted genes, relevant biological pathways, alternative splicing (AS) events regulated SRSF1. Results consistently upregulated both samples lines. Diminishing resulted reduced invasion increased while overexpressing led enhanced growth, decreased apoptosis. Mechanistically, Gene Ontology (GO) analysis, Kyoto Encyclopedia Genes Genomes (KEGG) Set Enrichment Analysis (GSEA) revealed that closely associated with dysregulation protein targeting processes, location cytosolic ribosome, extracellular matrix (ECM), proteinaceous matrix, along PI3K-AKT pathway, Wnt HIPPO pathway. Transcriptome analysis identified AS modulated especially (Skipped Exon) SE (Mutually exclusive Exons) MXE events, revealing potential roles molecules mRNA surveillance, degradation, transport during development. confirmed knockdown occurrence SRRM2, DMKN, SCAT1 Conclusions Our results highlight oncogenic high promoting progression, further explore mechanisms action. significant involvement development suggests utility therapeutic target

Language: Английский

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A genome-wide association study identified 10 novel genomic loci associated with intrinsic capacity

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Abstract In 2015, the World Health Organization introduced concept of intrinsic capacity (IC), a composite all individual-level attributes that contribute to healthy aging. To investigate genetic basis IC, we used data from UK Biobank (UKB; N=44,631) and Canadian longitudinal study on aging (CLSA; N=13,085). We estimated SNP-based heritability (h 2 SNP ) at 25.2% in UKB 19.5% CLSA. A Genome-Wide Association Study (GWAS) identified 38 independent SNPs for IC across 10 genomic loci 4,289 candidate mapped 197 genes. Post-GWAS analysis revealed role these genes cellular processes such as cell proliferation, immune function, metabolism, neurodegeneration, with high expressions muscle, heart, brain, adipose, tibial nerve tissues. Of 52 traits tested, 23 showed significant correlations higher loading was associated scores. This is first identify variants pathways providing foundation future research

Language: Английский

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Predicting immune status and gene mutations in stomach adenocarcinoma patients based on inflammatory response-related prognostic features

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

Published: April 9, 2025

Stomach adenocarcinoma (STAD) is an aggressive malignant tumor. Herein, we characterized the prognosis based on inflammatory response-related features and evaluated their potential impact survival immune status of STAD patients. Inflammation-related genes obtained from public databases were used to analyze response scores samples. The differentially expressed (DEGs) between adjacent gastric tissue then analyzed using "limma" package. Genes associated with intersection inflammation-related DEGs. key screened by last absolute shrinkage selection operator (LASSO) Cox stepwise regression analyses construct prognostic models nomograms. tumor dysfunction exclusion (TIDE) algorithm was assess differences in immunotherapy high- low-risk groups explore gene mutation signatures R software maftools In addition, GSEA predict pathway characteristics different subgroups. Finally, scratch transwell assays performed role SERPINE1 cells. We found that a high-inflammatory group poor 14 DEGs out 126 identified be patients, nomograms constructed subsequently (SLC7A1, CD82, ROS1 SLC7A2) demonstrated good predictive performance terms STAD. Patients high-risk had higher StromalScore TIDE scores. It also patients may have burden. Enrichment analysis revealed significant enrichment epithelial-mesenchymal transition, angiogenesis KRAS pathways group. In-vitro experiments showed down-regulation attenuated migratory invasive abilities AGS This study provides new insights into prediction for perspective response.

Language: Английский

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The Impact of Long Noncoding RNAs in Tissue Regeneration and Senescence

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 119 - 119

Published: Jan. 9, 2024

Overcoming senescence with tissue engineering has a promising impact on multiple diseases. Here, we provide an overview of recent studies in which cellular was inhibited through the up/downregulation specific lncRNAs. This approach prevented bones, joints, nervous system, heart, and blood vessels, potential regeneration prevention osteoarthritis osteoporosis, as well neurodegenerative cardiovascular Senescence skin liver could also be regulation levels lncRNAs, resulting rejuvenation cells from these organs their protection disease. From exciting achievements, support are not restricted to stem cells, propose lncRNA RNA or gene therapies prospective preventive therapeutic against aging aging-related

Language: Английский

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Identification of TGF-β signaling-related molecular patterns, construction of a prognostic model, and prediction of immunotherapy response in gastric cancer

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

Published: Nov. 18, 2022

Background: TGF-β signaling pathway plays an essential role in tumor progression and immune responses. However, the link between pathway-related genes (TSRGs) clinical prognosis, microenvironment (TME), immunotherapy gastric cancer is unclear. Methods: Transcriptome data related of were downloaded from Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases, 54 TSRGs obtained Molecular Signatures Database (MSigDB). We systematically analyzed expression profile characteristics 804 samples examined differences clinicopathological features, TME among different molecular subtypes. Subsequently, TGF-β-related prognostic models constructed using univariate least absolute shrinkage selection operator (LASSO) Cox regression analysis to quantify degree risk each patient. Patients divided into two high- low-risk groups based on median score. Finally, sensitivity checkpoint inhibitors (ICIs) anti-tumor agents was assessed patients groups. Results: identified distinct subgroups. Compared cluster B, A exhibits immunosuppressive with a shorter overall survival (OS). Then, novel TGF-β-associated model, including SRPX2, SGCE, DES, MMP7, KRT17, constructed, score demonstrated as independent factor for patients. Further studies showed that group, characterized by higher mutation burden (TMB), proportion high microsatellite instability (MSI-H), immunophenoscore (IPS), lower dysfunction exclusion (TIDE) score, had better linked response rate immunotherapy. In addition, drug strongly correlated. Conclusion: These findings highlight importance TSRGs, deepen understanding microenvironment, guide individualized

Language: Английский

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