RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Growing interest toward RNA modification in cancer has inspired the exploration of gene sets related to multiple modifications. However, a comprehensive elucidation clinical value various modifications breast is still lacking. This study aimed provide strategy based on modification-related genes for predicting therapy response and survival outcomes patients. Genes thirteen patterns were integrated establishing nine-gene-containing signature-RMscore. Alterations tumor immune microenvironment featured by different RMscore levels assessed bulk transcriptome, single-cell transcriptome genomics analyses. The biological function key RMscore-related molecules was investigated cellular experiments vitro vivo, using flow cytometry, immunohistochemistry immunofluorescence staining. raised an effective patients after well-rounded investigation genes. With great performance patient prognosis, high proposed this represented suppressive resistance, including adjuvant chemotherapy PD-L1 blockade treatment. As contributor RMscore, inhibition WDR4 impaired progression significantly as well participated regulating cell cycle mTORC1 signaling pathway via m7G modification. Briefly, developed promising tactics achieve prediction probabilities treatment

Язык: Английский

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Identification and targeting of cancer-associated fibroblast signature genes for prognosis and therapy in Cutaneous melanoma

Computers in Biology and Medicine, Год журнала: 2023, Номер 167, С. 107597 - 107597

Опубликована: Окт. 18, 2023

Язык: Английский

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Epigenetic deregulation in breast cancer microenvironment: Implications for tumor progression and therapeutic strategies

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 174, С. 116559 - 116559

Опубликована: Апрель 10, 2024

Breast cancer comprises a substantial proportion of diagnoses in women and is primary cause cancer-related mortality. While hormone-responsive cases generally have favorable prognosis, the aggressive nature triple-negative breast presents challenges, with intrinsic resistance to established treatments being persistent issue. The complexity intensifies emergence acquired resistance, further complicating management cancer. Epigenetic changes, encompassing DNA methylation, histone RNA modifications, non-coding RNAs, are acknowledged as crucial contributors heterogeneity unique epigenetic landscape harbored by each cellular component within tumor microenvironment (TME) adds great diversity intricate regulations which influence therapeutic responses. TME, sophisticated ecosystem non-cellular elements interacting cells, establishes an immunosuppressive fuels processes such growth, angiogenesis, extracellular matrix remodeling. These factors contribute challenging conditions treatment fostering hypoxic environment, inducing metabolic stress, creating physical barriers drug delivery. This article delves into complex connections between response, underlying vital interactions TME. To restore sensitivity treatment, it emphasizes need for combination therapies considering changes specific individual members Recognizing pivotal role epigenetics comprehending specificities TME essential devising more effective strategies. development reliable biomarkers patient stratification will facilitate tailored precise approaches.

Язык: Английский

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Autophagy Deficiency Induced by SAT1 Potentiates Tumor Progression in Triple‐Negative Breast Cancer

Advanced Science, Год журнала: 2024, Номер unknown

Опубликована: Июль 29, 2024

Aggressive triple-negative breast cancer (TNBC) still lacks approved targeted therapies, requiring more exploration of its underlying mechanisms. Previous studies have suggested a potential role SAT1 (Spermidine/Spermine N1-acetyltransferase 1) in cancer, which needs to be further elucidated cancer. In this study, highly expressed TNBC signified worse patient prognoses. And knockdown effectively inhibited the proliferation and migration abilities cells vitro vivo. terms mechanism, transcription factor JUN enhanced transcriptional activity by binding promoter region. Then, protein cytoplasm engaged directly with YBX1 for sustaining stability via deubiquitylation mediated E3 ligase HERC5. Further, was found suppress autophagy remarkably stabilization mTOR mRNA accumulation YBX1-mediated methyl-5-cytosine (m5C) modification. These findings proved that drives progression through SAT1/YBX1/mTOR axis, may provide candidate therapy advanced TNBC.

Язык: Английский

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Identification of a basement membrane gene signature for predicting prognosis and estimating the tumor immune microenvironment in prostate cancer

Aging, Год журнала: 2024, Номер 16(2), С. 1581 - 1604

Опубликована: Янв. 17, 2024

Basement membrane plays an important role in tumor invasion and metastasis, which is closely related to prognosis. However, the prognostic value biology of basement genes (BMGs) prostate cancer (PCa) remain unknown. In TCGA training set, we used differentially expressed gene analysis, protein-protein interaction networks, univariate multivariate Cox regression, least absolute shrinkage selection operator regression construct a membrane-related risk model (BMRM) validated its effectiveness MSKCC validation set. Furthermore, accurate nomogram was constructed improve clinical applicability. Patients with PCa were divided into high-risk low-risk groups according optimal cut-off score (BMRS). It found that BMRS significantly associated RFS, T-stage, Gleason score, microenvironmental characteristics patients. Further analysis showed grouping immune microenvironment characteristics, checkpoint inhibitors, chemotherapeutic drug sensitivity. this study, developed new BMGs-based determine BMGs PCa. Finally, confirmed THBS2, key BMRM, may be link occurrence progression This study provides novel perspective assess prognosis patients clues for future personalized treatment regimens.

Язык: Английский

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A novel basement membrane-related gene signature for predicting prognosis of HNSCC

Medicine, Год журнала: 2025, Номер 104(3), С. e41316 - e41316

Опубликована: Янв. 17, 2025

In recent years, a notably heterogeneous malignant tumor, squamous cell carcinoma of the head and neck (HNSCC), has received increasing attention, with no significant improvement in its survival rate. The rapid increase number prognostic models associated HNSCC been observed due to accuracy, which offers crucial clinical benefits. 10 genes were selected from 222 human basement membrane analysis this article. gene pool was narrowed through different classifications intersections, followed by univariate Cox regression analysis. Genes statistical significance underwent further Least Absolute Shrinkage Selection Operator (LASSO) analysis, resulting final selection genes. data images extracted Human Protein Atlas database utilized confirm differential expression corresponding Multivariate employed develop nomogram, nomogram assessed additional decision curve (DCA). Gene Expression Omnibus validation set used validate established model. Finally, between high- low-risk score groups, Set Enrichment Analysis, immune correlation drug sensitivity conducted paper. ITGA5 , SPOCK1 EVA1C TINAGL1 LAMB4 ADAMTS1 EGFL6 GPC2 BGN ITGA2B successfully developed as membrane-associated risk models. time-dependent receiver operating characteristic (timeROC) illustrated that prediction accuracy outperformed indicators, commonly adopted practice, consisting age, stage, gender, T-staging, N-staging. 3-year timeROC area under value 0.679. This model demonstrates reliable ability assess prognosis patients. addition, specific potential biomarkers explored research.

Язык: Английский

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Comprehensive analysis of metabolism-related gene biomarkers reveals their impact on the diagnosis and prognosis of triple-negative breast cancer

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Апрель 11, 2025

Язык: Английский

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Basement membrane-related MMP14 predicts poor prognosis and response to immunotherapy in bladder cancer

BMC Cancer, Год журнала: 2024, Номер 24(1)

Опубликована: Июнь 19, 2024

Abstract Background Basement membrane (BM) is an important component of the extracellular matrix, which plays role in growth and metastasis tumor cells. However, few biomarkers based on BM have been developed for prognostic assessment prediction immunotherapy bladder cancer (BLCA). Methods In this study, we used BLCA public database to explore relationship between BM-related genes (BMRGs) prognosis. A novel molecular typing was performed using consensus clustering. LASSO regression construct a signature BMRGs, its with prognosis explored survival analysis. The pivotal BMRGs were further analyzed assess clinical characteristics immune landscape. Finally, immunohistochemistry detect expression hub gene patients who underwent surgery or received checkpoint inhibitor (ICI) our hospital. Results We comprehensively BLCA, established prognostic-related independent influence BLCA. screened validated gene-MMP14 database. addition, found that MMP14 muscle invasive (MIBC) significantly higher high had poorer response ICI treatment cohort. Conclusions Our findings highlighted satisfactory value suggested may be potential biomarker predicting

Язык: Английский

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The epigenetic-modified downregulation of LOXL1 protein mediates EMT in bladder epithelial cells exposed to benzo[a]pyrene and its metabolite BPDE

International Immunopharmacology, Год журнала: 2024, Номер 142, С. 113232 - 113232

Опубликована: Сен. 27, 2024

Язык: Английский

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Identification of a basement membrane-related genes signature to predict prognosis, immune landscape and guide therapy in gastric cancer

Medicine, Год журнала: 2023, Номер 102(39), С. e35027 - e35027

Опубликована: Сен. 29, 2023

The basement membrane is an essential defense against cancer progression and intimately linked to the tumor immune microenvironment. However, there limited research comprehensively discussing potential application of membrane-related genes (BMRGs) in prognosis evaluation immunotherapy gastric (GC). RNA-seq data clinical information GC patients were collected from TCGA GEO database. Prognosis-associated BMRGs filtered via univariate Cox regression analysis. 4-BMRGs signatures constructed by lasso regression. Prognostic predictive accuracy signature was appraised with survival analysis, receiver operating characteristic curves, nomogram. Gene set enrichment analysis (GSEA), gene ontology, variation performed dig out mechanisms functions. Estimate algorithm ssGSEA used for assessing microenvironment immunological characteristics. Identification molecular subtypes consensus clustering. Drug sensitivity using "pRRophetic" R package. Immunotherapy validation cohort. A constructed, which could excellently predict patient (5-year AUC value 0.873). Kaplan-Meier analyses showed that OS-independent prognostic factor, higher risk scores associated shorter OS. high-risk subgroup exhibits a abundance cell infiltration, such as macrophages. Additionally, we observed strong correlation between 2 (LUM, SPARC) cells CD8 + T appears be more sensitive Axitinib, DMOG, Gemcitabine Docetaxel pRRophetic Furthermore, cohort received therapy revealed group who underwent checkpoint inhibitor treatment exhibited better response rates. Pan-cancer also shows are strongly carcinogenic pathways. has demonstrated reliability predicting patient's assist formulation strategies.

Язык: Английский

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