Neoplasia, Год журнала: 2024, Номер 60, С. 101116 - 101116
Опубликована: Дек. 25, 2024
Язык: Английский
Biology Direct, Год журнала: 2024, Номер 19(1)
Опубликована: Июнь 25, 2024
Abstract Background Prostate cancer (PCa) is the second leading cause of tumor-related mortality in men. Metastasis from advanced tumors primary death among patients. Identifying novel and effective biomarkers essential for understanding mechanisms metastasis PCa patients developing successful interventions. Methods Using GSE8511 GSE27616 data sets, 21 metastasis-related genes were identified through weighted gene co-expression network analysis (WGCNA) method. Subsequent functional these was conducted on set (GSCA) website. Cluster utilized to explore relationship between genes, immune infiltration PCa, efficacy targeted drug IC50 scores. Machine learning algorithms then employed construct diagnostic prognostic models, assessing their predictive accuracy. Additionally, multivariate COX regression highlighted significant role POLD1 examined its association with DNA methylation. Finally, molecular docking immunohistochemistry experiments carried out assess binding affinity drugs impact prognosis. Results The study using WGCNA method, which found be associated damage, hormone AR activation, inhibition RTK pathway. confirmed a correlation metastasis, particularly context immunotherapy therapy drugs. A model combining multiple machine showed strong capabilities diagnosis, while transfer LASSO algorithm also yielded promising results. emerged as key metastatic showing associations Molecular supported high PCa-targeted Immunohistochemistry further validated that increased expression linked poor prognosis Conclusions developed models provide substantial value prostate cancer. discovery biomarker related offers avenue enhancing treatment metastasis.
Язык: Английский
Процитировано
23
Redox Biology, Год журнала: 2024, Номер 74, С. 103228 - 103228
Опубликована: Июнь 7, 2024
Therapy-induced senescent tumor cells have emerged as significant drivers of recurrence and disease relapse. Interestingly, reactive oxygen species (ROS) production its associated redox signaling networks are intertwined with initiation establishment therapy-induced senescence. influence neighboring the microenvironment via their bioactive secretome known senescence-associated secretory phenotype (SASP). The intracellular effects ROS dose context-dependent. Under normal physiological conditions, is involved in various signalling pathways cellular processes important for maintenance homeostasis, such balance, stress response, inflammatory signalling, cell proliferation death among others. However excess accompanied by a pro-oxidant can engender oxidative DNA damage, triggering In this review, we discuss role state dynamics fine-tuning homeostatic that drive fate towards senescence establishment, well stimulating SASP production. We also offer insights into interventional strategies, specifically senotherapeutics, could potentially leverage on modulation antioxidant pathways. Lastly, evaluate possible implications rewiring during escape from senescence, an emerging area research. envision examining through lens, integrated time-resolved single-cell RNA sequencing combined spatiotemporal multi-omics, further enhance our understanding functional heterogeneity. This aid identification targetable nodes to reduce relapse, inform strategies development broad-spectrum senotherapeutics. Overall, review aims delineate redox-driven mechanisms which contribute biology beyond, while highlighting recurrence.
Язык: Английский
Процитировано
5
Cell & Bioscience, Год журнала: 2025, Номер 15(1)
Опубликована: Янв. 23, 2025
Abstract Background Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure drug resistance. However, the lack of a quick convenient approach determine intratumoral (eITH) limit application eITH in clinical settings. Here, we aimed develop tool that can evaluate using DNA methylation profiles bulk tumors. Methods Genomic three laser micro-dissected tumor regions, including digestive tract surface, central bulk, invasive front, was extracted formalin-fixed paraffin-embedded sections colorectal cancer patients. The genome-wide were generated with array. most variable methylated probes selected construct methylation-based (MeHEG) estimation deconvolve proportion each reference region support vector machine model-based method. A PCR-based assay for quantitative analysis (QASM) developed specifically status CpG MeHEG at single-base resolution realize fast evaluation heterogeneity. Results In discovery set 79 patients, differentially CpGs among regions found. 7 representative identified subsequently algorithm. We validated its performance deconvolution an independent cohort. addition, showed significant association MeHEG-based genomic mutation copy number variation our in-house TCGA cohorts. Besides, found patients higher score had worse disease-free overall survival outcomes. Finally, dynamic change based on cells under treatment drugs. Conclusion By developing 7-loci panel learning combined QASM application, present valuable method evaluating algorithm offers novel insights into perspective, potentially enriching current knowledge complexity providing new research applications biology.
Язык: Английский
Процитировано
0
Bioengineering & Translational Medicine, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Abstract Tumor resistance to chemotherapy is a common cause of cancer recurrence in patients with head and neck squamous cell carcinoma. The goal this study establish characterize chemoresistant laryngeal model test its potential utility for chemosensitizing therapy. At the genotypic level, RNA sequencing confirmed that cells acquired putative upregulated docetaxel‐resistant (DR) genes (e.g., TUBB3, CYP24A1) signaling pathways PI3K/mTOR, autophagy). For phenotypic analysis, DR were co‐cultured fibroblasts 2‐channel microfluidic chip mimics hypoxic tumor core vivo. A drug sensitivity chemosensitizer, metformin (MTF), was performed on tumor‐on‐a‐chip. Compared non‐treated controls, MTF‐primed exhibit higher docetaxel (DTX), is, death. Collectively, resistance‐acquired displayed presumed profiles chemoresistance providing viable option testing new therapeutic strategies restoring DTX.
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Июнь 6, 2024
Cancer-associated fibroblasts (CAFs) are the primary stromal cells found in tumor microenvironment, and display high plasticity heterogeneity. By using single-cell RNA-seq technology, researchers have identified various subpopulations of CAFs, particularly highlighting a recently subpopulation termed antigen-presenting CAFs (apCAFs), which largely unknown.
Язык: Английский
Процитировано
2
Clinical and Molecular Hepatology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 30, 2024
Transmembrane 4 L six family member 1 (TM4SF1) is highly expressed in and contributes to the progression of various malignancies. However, how it modulates hepatocellular carcinoma (HCC) senescence remains be elucidated.
Язык: Английский
Процитировано
2
Biology Direct, Год журнала: 2024, Номер 19(1)
Опубликована: Ноя. 12, 2024
Gliomas represent a highly aggressive class of tumors located in the brain. Despite availability multiple treatment modalities, prognosis for patients diagnosed with glioma remains unfavorable. Therefore, further exploration new biomarkers is crucial to enhance prognostic assessment and investigate more effective options. In this research, we utilized machine learning techniques assess significance genes related angiogenesis epithelial-mesenchymal transition (EMT) context patients. The random forest algorithm highlighted CALU, analysis indicated that effect CALU on progression may be regulated by MYC. Different approaches were employed our investigation uncover associated EMT glioma. Our findings verify connection between these glioma, as well results immunotherapeutic interventions. Notably, through experimental verification, identified marker inhibiting expression can impede
Язык: Английский
Процитировано
2
Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)
Опубликована: Дек. 31, 2024
Colorectal cancer (CRC) is characterized by poor responsiveness to immune evasion and immunotherapy. RNA 7-methylguanine (m7G) modification plays a key role in tumorigenesis. However, the mechanisms which m7G-modified metabolism affects tumor progression are not fully understood, nor contribution of CRC microenvironment. The expression levels Methyltransferase-like 1 (METTL1) m7G human tissues were determined. In this study, effect METTL1 on was evaluated, PKM mRNA confirmed, level PKM2 protein detected, mechanism involved RT‒qPCR, Western blot, stability analysis RIP analysis. Lactate H3K9 lactylation (H3K9la) induced METTL1/PKM2 analyzed via extracellular acidification rate (ECAR) lactic acid assays. Cut&Run used detect METTL1/PKM2-induced CD155 (PVR) transcription. addition, knockout mice studied vivo with blockers. We demonstrated that enhances acting mRNA, leading increased glycolysis. Specifically, mediates methylation its encoded PKM2, turn glycolysis, promotes H3K9la, activates transcription, creating positive feedback loop. Moreover, dimer nuclear translocation activated evasion. Our findings reveal general METTL1/PKM2/H3K9la signaling regulates highlight targeting as potential strategy for
Язык: Английский
Процитировано
2
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2024, Номер 1879(6), С. 189178 - 189178
Опубликована: Сен. 4, 2024
Язык: Английский
Процитировано
1
BioFactors, Год журнала: 2024, Номер unknown
Опубликована: Окт. 31, 2024
Abstract Most patients with non‐small cell lung cancer (NSCLC) are diagnosed at an advanced stage of the disease, which complicates treatment due to a heightened risk metastasis. Consequently, timely identification biomarkers associated lymph node metastasis is essential for improving clinical management NSCLC patients. In this research, WGCNA algorithm was utilized pinpoint genes linked in NSCLC. A cluster analysis carried out investigate how these correlate prognosis and outcomes immunotherapy Following this, diagnostic prognostic models were created validated through various machine learning methodologies. The random forest technique highlighted importance ARHGAP11A, leading in‐depth examination its role By analyzing 78 tissue chip samples from patients, study confirmed association between ARHGAP11A expression, patient prognosis, Finally, influence on cells assessed function experiments. This research identify 25 that related metastasis, clarifying their connections tumor invasion, growth, activation stemness pathways. Cluster revealed significant associations NSCLC, especially concerning targeted treatments. system combines approaches demonstrated strong efficacy forecasting both diagnosis Importantly, identified as key gene Molecular docking analyses suggested has affinity therapies within Additionally, immunohistochemical assessments higher levels expression unfavorable Experiments showed reducing can hinder proliferation, traits cells. investigation reveals novel insight may potential biomarker connected Moreover, ability diminish characteristics, presenting promising opportunity strategies condition.
Язык: Английский
Процитировано
0