Identification of anoikis-related molecular patterns and the novel risk model to predict prognosis, tumor microenvironment infiltration and immunotherapy response in bladder cancer DOI Creative Commons

Luochen Zhu,

Xiao Feng, Yi Hou

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 27, 2024

Background Anoikis, a unique form of cell death, serves as vital part the organism's defense by preventing shedding cells from re-attaching to incorrect positions, and plays pivotal role in cancer metastasis. Nonetheless, specific mechanisms among anoikis, clinical prognosis tumor microenvironment (TME) bladder (BLCA) are insufficiently understood. Method BLCA patients were classified into different anoikis subtypes based on expression candidate anoikis-related genes (ARGs), differences clinicopathological features, TME, immune infiltration, checkpoints between two analyzed. Next, TCGA cohort randomized train test groups 1:1 ratio. Subsequently, model was constructed predict via utilizing univariate Cox, LASSO multivariate Cox analyses, validated internally externally. Moreover, relationships risk score clinicopathologic immunotherapy response, antitumor drug sensitivity also In addition, representative evaluated using immunohistochemistry specimens, lines, functional experiments performed determine biological behavior hub gene PLOD1. Result Two definite subgroups identified. Compared ARGcluster A, assigned B characterized an immunosuppressive worse prognosis. Then, model, including PLOD1, EHBP1, CSPG4, constructed, low-risk group better accurate nomogram built improve applicability combining age, stage Score. infiltration features differed significantly high- groups. We found that exhibited lower dysfunction exclusion score, higher immunophenoscore (IPS), had more immunotherapy. Eventually, levels three verified our experiment, knockdown PLOD1 could inhibit invasion migration abilities lines. Conclusion These results demonstrated new direction precision therapy for BLCA, indicated ARGs might be helpful predicting therapeutic targets BLCA.

Язык: Английский

Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target DOI Creative Commons
Yaxuan Wang, Jinfeng Wang, Lu Zhang

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(7), С. 1 - 20

Опубликована: Март 20, 2024

Abstract YARS is responsible for catalysing the binding of tyrosine to its cognate tRNA and plays a crucial role in basic biosynthesis. However, biological functions bladder cancer remains be proven. We analysed variations YARS1 expression survival using multiple data sets, including TCGA‐BLCA, GSE13507 cancer‐specific tissue microarrays. Furthermore, we explored transcriptome data. Our findings revealed noteworthy correlation between immune infiltration cancer, as determined XCELL algorithm single‐cell analysis. In addition, employed TIDE evaluate responsiveness different cohorts checkpoint therapy. investigated regulatory associations various aspects senescence, ferroptosis stemness. Finally, established ceRNA network that directly linked overall prognosis, can serve prognostic biomarker cancer; interaction with MYC has implications cell Moreover, identified potential therapeutic target cancer.

Язык: Английский

Процитировано

18
DARS2 Promotes Bladder Cancer Progression by Enhancing PINK1-Mediated Mitophagy DOI Creative Commons
Dongqing Li, Hang Su, Xiaolin Deng

и другие.

International Journal of Biological Sciences, Год журнала: 2025, Номер 21(4), С. 1530 - 1544

Опубликована: Янв. 27, 2025

Globally, bladder cancer is the tenth most common cancer. Mitophagy, a critical process regulating mitochondrial quantity and quality, has attracted increasing attention for its pivotal function in Nonetheless, roles underlying mechanisms are yet to be elucidated. Therefore, this study, 16 mitophagy-related genes were screened construct robust prognostic model with exceptional predictive accuracy outcomes of patients Of these genes, DARS2 was identified as key regulator that significantly affected progression. The findings established promoted G1-to-S phase transition by upregulating CDK4 expression, thereby suppressing cellular senescence driving cell proliferation. In addition, augmented PINK1 leading increased PINK1-mediated mitophagy. Both vitro vivo experiments confirmed inhibited facilitated tumor progression enhancing observations from study have provided novel insights into multifaceted DARS2-mediated mitophagy Targeting regulation promising therapeutic strategy improve

Язык: Английский

Процитировано

1
The roles of FGFR3 and c-MYC in urothelial bladder cancer DOI Creative Commons

Dereje E. Bogale

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 20, 2024

Abstract Bladder cancer is one of the most frequently occurring cancers worldwide. At diagnosis, 75% urothelial bladder cases have non-muscle invasive while 25% muscle or metastatic disease. Aberrantly activated fibroblast growth factor receptor (FGFR)-3 has been implicated in pathogenesis cancer. Activating mutations FGFR3 are observed around 70% NMIBC and ~ 15% MIBCs. Activated leads to ligand-independent dimerization activation downstream signaling pathways that promote cell proliferation survival. an important therapeutic target cancer, clinical studies shown benefit FGFR inhibitors a subset patients. c-MYC well-known major driver carcinogenesis commonly deregulated oncogenes identified human cancers. Studies antitumor effects inhibition dependent cells other may be mediated through c-MYC, key effector involved tumorigenesis. This review will summarize current general understanding MYC alterations role dysregulation with possible implications.

Язык: Английский

Процитировано

7
Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants DOI Creative Commons
Muhammad Tufail, Yuqi Huang,

Jia-Ju Hu

и другие.

Aging and Disease, Год журнала: 2024, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2024

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling determinants of fate. Beginning with an overview aging's significance in explores processes, changes, molecular pathways influencing senescence. The senescence as a dual mechanism acting suppressor contributor, focusing on its impact therapy response. highlights opportunities for cancer therapies that target further examines senescence-associated secretory phenotype strategies to modulate aging influence tumor behavior. Additionally, mechanisms escape cells, emphasizing their prognosis resistance therapy. article addresses current advances, unexplored aspects, future perspectives understanding cancer.

Язык: Английский

Процитировано

6
Implications of c-Myc in the pathogenesis and treatment efficacy of urological cancers DOI
Kiavash Hushmandi, Seyed Hassan Saadat, Mehdi Raei

и другие.

Pathology - Research and Practice, Год журнала: 2024, Номер 259, С. 155381 - 155381

Опубликована: Июнь 1, 2024

Язык: Английский

Процитировано

4
DET induces apoptosis and suppresses tumor invasion in glioma cells via PI3K/AKT pathway DOI Creative Commons
Rui Zhao, Mengran Wang, Zeyu Wu

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 14

Опубликована: Янв. 9, 2025

Gliomas, particularly glioblastomas (GBM), are highly aggressive with a poor prognosis and low survival rate. Currently, deoxyelephantopin (DET) has shown promising anti-inflammatory anti-tumor effects. Using clinical prognostic analysis, molecular docking, network pharmacology, this study aims to explore the primary targets signaling pathways identify novel GBM treatment approaches. PharmMapper, chemical structure of DET was examined for possible after being acquired from PubChem. GBM-related were obtained through multi-omics A protein-protein interaction (PPI) constructed using Cytoscape STRING, target binding evaluated docking. Enrichment analysis conducted Metascape. The effects on cell invasion, apoptosis, proliferation assessed in vitro assays, including Transwell, EDU, CCK8, flow cytometry. Western blot performed examine components PI3K/AKT pathway. Among sixty-four shared identified, JUN CCND1 most frequently observed. demonstrated that influenced MAPK pathways. In Transwell significantly inhibited invasive behavior glioma cells. further confirmed downregulation EGFR, JUN, PI3K/AKT. inhibits proliferation, apoptosis via modulating pathway, highlighting its potential as therapeutic strategy treatment.

Язык: Английский

Процитировано

0
Development and functional validation of a disulfidoptosis-related gene prognostic model for lung adenocarcinoma based on bioinformatics and experimental validation DOI Creative Commons
Tao Shen,

Zhuming Lu,

Sisi Yang

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 10, 2025

Background Disulfidoptosis is increasingly linked to cancer progression, yet its immunological impacts and prognostic value in lung adenocarcinoma (LUAD) remain poorly understood. This study aims delineate the predictive significance of disulfidoptosis-related genes (DRGs) LUAD, their potential as therapeutic targets, interaction with tumor microenvironment. Methods We analyzed expression profiles 23 DRGs survival data, performing consensus clustering identify molecular subtypes. Survival analysis gene set variation (GSVA) were used explore cluster differences. Key selected for Cox LASSO regression develop a model. Tensin4 (TNS4), key model, was further evaluated through immunohistochemistry (IHC) LUAD normal tissues knockdown experiments vitro . Results Two clusters identified, 225 differentially expressed genes. A six-gene signature developed, which classified patients into high- low-risk groups, showing significant The risk score independently predicted prognosis correlated immunotherapy responses. IHC showed elevated TNS4 levels tissues, while reduced both cell proliferation migration. Conclusion highlights role validated offering new avenues targeted therapies, potentially improving treatment outcomes.

Язык: Английский

Процитировано

0
Prognostic value of body adipose tissue parameters in cancer patients treated with immune checkpoint inhibitors DOI Creative Commons
Yan Li, Yean Yu,

Kun Lv

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 12, 2025

Objective This study aims to explore the relationship between body adipose tissue characteristics and clinical outcomes in cancer patients receiving immune checkpoint inhibitor (ICI) therapy. Methods We conducted an extensive literature search across three major online databases—Embase, PubMed, Cochrane Library—to identify studies examining link treatment undergoing ICI therapy, from inception of each database until February 20, 2024. The quality included was evaluated using Newcastle-Ottawa Scale. primary analyzed were hazard ratios (HRs) for overall survival (OS) progression-free (PFS), as well odds (ORs) disease control rate (DCR). Pooled estimates 95% confidence intervals (CIs) calculated. Results A total 23 included, encompassing 2741 patients. analysis revealed that with higher levels visceral (VAT) exhibited significantly improved OS (HR: 0.72, CI: 0.59–0.89, p < 0.001) PFS 0.80, 0.67–0.96, = 0.015), along a DCR (OR: 1.81, 1.26–2.60, 0.001), compared those lower VAT levels. Additionally, increased subcutaneous (SAT) associated better 0.69, 0.58–0.82, 0.82, 0.68–1.00, 0.049), 1.99, 1.15–3.44, 0.014). Elevated (TAT) also linked longer 0.73, 0.55–0.97, 0.028). However, visceral-to-subcutaneous ratio (VSR) shorter 1.43, 1.09–1.87, 0.010). No significant found TAT 0.81, 0.54–1.23, 0.332) VSR 1.20, 0.95–1.51, 0.131) ICI-treated Conclusion highlights prognostic relevance SAT predicting response ICIs. These findings suggest assessments should be incorporated into evaluations this patient population.

Язык: Английский

Процитировано

0
Prognostic significance and immune microenvironment infiltration patterns of hypoxia and endoplasmic reticulum stress-related genes in gastric cancer DOI Creative Commons
Libin Li, Yizhi Liang, Wenfang Xu

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 21, 2025

Gastric cancer (GC) is a prevalent malignant neoplasm within the digestive system, accounting for approximately 740,000 deaths globally each year, significantly impacting patients' quality of life and survival rates. The objective this investigation was to elucidate expression patterns Hypoxia Endoplasmic Reticulum Stress-related Differentially Expressed Genes (HERSRDEGs) in GC their association with prognostic outcomes patients. Utilizing Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases, datasets were retrieved, standard normalization performed. Differential analysis conducted using DESeq2, while somatic mutations copy number variations examined maftools GISTIC2.0. Spearman's correlation assessed interplay between HERSRDEGs across datasets. Functional enrichment analyses carried out clusterProfiler Ontology (GO) Kyoto Encyclopedia Genomes (KEGG) pathways, alongside Set Enrichment Analysis (GSEA). A risk model obtained by utilizing univariate Cox regression R package. We employed RT-qPCR validate mRNA levels five genes that impact gastric human adenocarcinoma tissues. acquired data revealed 19 including ANGPT2, CXCL8, AURKA exhibiting significant variation controls. In analysis, total genes-ANGPT2, CD36, EGR1, NOX4, TLR2-emerged as statistically significant, correlating strongly overall survival. LASSO featuring NOX4 yielded score formula capable predicting patient outcomes. Furthermore, multivariate highlighted RiskScore, age stage predictors. immune infiltration notable differences populations cells, such Natural Killer cells T-helper when comparing high-risk low-risk groups. conclusion, elucidates involvement progression potential biomarkers.

Язык: Английский

Процитировано

0
Metformin upregulates circadian gene PER2 to inhibit growth and enhance the sensitivity of glioblastoma cell lines to radiotherapy via SIRT2/G6PD pathway DOI Creative Commons
Hai-Liang Li, Zheng Feei,

Yang Wanfu

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Март 17, 2025

Glioblastoma multiform (GBM) is considered the deadliest brain cancer. Standard therapies are followed by poor patient's survival outcomes, so novel and more efficacious therapeutic strategies imperative to tackle this scourge. Metformin has been reported have anti-cancer effects. However, precise mechanism underlying these effects remains elusive. A better understanding of its will inform future experimental designs exploring metformin as a potential adjuvant therapy for GBM. This research aimed elucidate molecular in GBM integrating proteomics transcriptomics. The study examined on cell lines using various methods. U87, U251 HA1800 were cultured modified through PER2 knockdown overexpression. Cell viability was assessed CCK8 assay, G6PDH activity intracellular NADPH+ levels measured with specific kits. ROS levels, mitochondrial membrane potential, cycle distribution apoptosis analyzed flow cytometry. RNA extracted transcriptomic analysis sequencing, while proteomic performed total protein from treated cells. WB detected proteins, RT-qPCR quantified gene expression. In vivo experiments, xenograft nude mice combining radiotherapy evaluated received IHC TUNEL staining expression assessment. Statistical analyses conducted Prism software identify significant group differences. We found that differential expressional genes proteins relating circadian rhythm enriched or transcriptomic. PER2, key gene, up-regulated when metformin. Furthermore, silent information regulator 2(SIRT2) down-regulated, G6PD just slightly increased lines. Meanwhile, production enzyme significantly decreased. Further validated inhibited growth up-regulating SIRT2/G6PD signaling pathway, enhancing radiotherapy(RT) sensitivity. also inhibition SIRT2 caused mediated PER2. pivotal role an effective regulator. Targeting clock modify rescue dysfunctional cells at level might be innovative way administer cancer chronotherapy maintain metabolic homeostasis real world practice.

Язык: Английский

Процитировано

0