Unveiling the role of YARS1 in bladder cancer: A prognostic biomarker and therapeutic target

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(7), P. 1 - 20

Published: March 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.

Language: Английский

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Understanding and overcoming resistance to immunotherapy in genitourinary cancers

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 17, 2024

The introduction of novel immunotherapies has significantly transformed the treatment landscape genitourinary (GU) cancers, even becoming standard care in some settings. One such type immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit system's ability to fight tumor cells. Despite profound impact these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage evade response identifying possible mechanisms behind resistance immunotherapy. In response, ICIs being combined with other treatments reduce attack through multiple cellular pathways. Additionally, novel, targeted strategies currently investigated develop innovative methods overcoming failure. This article presents comprehensive overview immunotherapy GU cancers as described literature. It explores studies identified genetic markers, cytokines, proteins may predict or we review current overcome this resistance, which include combination sequential therapies, insights into host profile, new therapies. Various approaches combine chemotherapy, therapy, vaccines, radiation studied an effort more effectively While each therapies shown efficacy clinical trials, deeper underscores potential particularly promising area research. Currently, several agents development, along identification key mediators involved resistance. Further is necessary identify predictors response.

Language: Английский

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Senescence-specific molecular subtypes stratify the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 19, 2025

Bladder cancer (BLCA) is notably associated with advanced age, characterized by its high incidence and mortality among the elderly. Despite promising advancements in models that amalgamate molecular subtypes treatment prognostic outcomes, considerable heterogeneity BLCA poses challenges to their universal applicability. Consequently, there an urgent need develop a new subtyping system focusing on critical clinical feature of BLCA: senescence. Utilizing unsupervised clustering Cancer Genome Atlas Program (TCGA)-BLCA cohort, we crafted senescence-associated classification precision quantification (Senescore). This method underwent systematic validation against established subtypes, strategies, immune tumor microenvironment (TME), relevance checkpoints, identification potential therapeutic targets. External validations were conducted using Xiangya IMvigor210 meta-cohort, multiplex immunofluorescence confirming correlation between Senescore, infiltration, cellular Notably, patients categorized within higher Senescore group predisposed basal subtype, showcased augmented harbored elevated driver gene mutations, exhibited increased secretory phenotype (SASP) factors expression transcriptome. poorer prognoses, these revealed greater responsiveness immunotherapy neoadjuvant chemotherapy. Our informed age-related features, accurately depict age-associated biological traits application BLCA. Moreover, this personalized assessment framework poised identify senolysis targets unique BLCA, furthering integration aging research into strategies.

Language: Английский

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CXCL6 Reshapes Lipid Metabolism and Induces Neutrophil Extracellular Trap Formation in Cholangiocarcinoma Progression and Immunotherapy Resistance

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

The chemokine CXCL6 is identified as a pivotal regulator of biological processes across multiple malignancies. However, its function in cholangiocarcinoma (CCA) underexplored. Tumor profiling for performed using public database. Both vitro and vivo experiments are utilized to evaluate the oncogenic effects on CCA. Additionally, RNA-Seq employed detect transcriptomic changes related expression CCA cells neutrophils. Molecular docking, fluorescence colocalization, Co-IP used elucidate direct interaction between JAKs CXCR1/2. LC-MS lipidomics explored impact immunotherapy vivo. upregulated tissues promoted proliferation metastasis Mechanistically, regulated CXCR1/2-JAK-STAT/PI3K axis via autocrine signaling, leading lipid metabolic reprogramming, neutrophil extracellular traps (NETs) formation by activating RAS/MAPK pathway Eventually, NETs induced resistance blocking CD8+T cell infiltration. modulates progression through reshaping metabolism. also mediates NETs, which may be potential therapeutic target biomarker

Language: Английский

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Nanomaterials: leading immunogenic cell death-based cancer therapies

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 9, 2024

The field of oncology has transformed in recent years, with treatments shifting from traditional surgical resection and radiation therapy to more diverse customized approaches, one which is immunotherapy. ICD (immunogenic cell death) belongs a class regulatory death modalities that reactivate the immune response by facilitating interaction between apoptotic cells releasing specific signaling molecules, DAMPs (damage-associated molecular patterns). inducers can elevate expression proteins optimize TME (tumor microenvironment). use nanotechnology shown its unique potential. Nanomaterials, due their tunability, targeting, biocompatibility, have become powerful tools for drug delivery, immunomodulators, etc., significant efficacy clinical trials. In particular, these nanomaterials effectively activate ICD, trigger potent anti-tumor response, maintain long-term tumor suppression. Different types nanomaterials, such as biological membrane-modified nanoparticles, self-assembled nanostructures, metallic mesoporous materials, hydrogels, play respective roles induction structures mechanisms action. Therefore, this review will explore latest advances application common discuss how they provide new strategies cancer therapy. By gaining deeper understanding mechanism action researchers develop precise effective therapeutic approaches improve prognosis quality life patients. Moreover, hold promise overcome resistance conventional therapies, minimize side effects, lead personalized treatment regimens, ultimately benefiting treatment.

Language: Английский

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ARID1A is a Coactivator of STAT5 that Contributes to CD8+ T Cell Dysfunction and Anti-PD-1 Resistance in Gastric Cancer

Pharmacological Research, Journal Year: 2024, Volume and Issue: 210, P. 107499 - 107499

Published: Nov. 15, 2024

ARID1A deletion mutation contributes to improved treatment of several malignancies with immune checkpoint inhibitors (ICIs). However, its role in modulating tumor microenvironment (TIME) gastric cancer (GC) remains unclear. Here, we report an increase CD8+ T cells infiltration GC patients ARID1A-mutation (MUT), which enhances sensitivity ICIs. Kaplan-Meier survival analysis showed that gastrointestinal benefit from immunotherapy. Transcriptome implicated regulates STAT5 downstream targets inhibit T-cell mediated toxicity. Integrated dual luciferase assay and ChIP-qPCR analyses indicated coordinated facilitate the transcription immunosuppressive factors TGF-β1 NOX4. recruited canonical BAF complex (cBAF) subunits, including SMARCB1 SMARCD1, sustain DNA accessibility. Downregulation reduced chromatin remodeling into configurations make more sensitive In addition, targeting effectively anti-PD-1 efficiency ARID1A-wild type (WT) patients. Taken together, is a coactivator STAT5, function as organizer ICIs resistance, effective strategy improve GC.

Language: Английский

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Correlation between long non-coding RNA MAFG-AS1 and cancer prognosis: a meta-analysis

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

Published: Dec. 7, 2023

Background MAF transcription factor G antisense RNA 1 (MAFG-AS1), a novel long non-coding discovered recently, was proved to be useful in predicting malignancy prognosis. Nevertheless, its association with cancer prognosis has been inconsistent. Therefore, this meta-analysis aimed explore the clinicopathological and prognostic significance of MAFG-AS1 diverse carcinomas. Methods Studies focused on expression as role cancers were thoroughly searched six electronic databases. The value malignancies assessed by hazard ratios (HRs) or odds (ORs). Additionally, GEPIA database utilized further strengthen our conclusion. Results A total 15 studies involving 1187 cases nine types recruited into meta-analysis. High significantly related advanced tumor stage (OR = 0.52, 95%CI [0.39, 0.69], P < 0.00001), earlier lymph node metastasis 3.62, [2.19, 5.99], worse differentiation 0.64, [0.43, 0.95], 0.03), poor overall survival (HR 1.94, [1.72, 2.19], 0.00001). No significant heterogeneity publication bias detected across studies. Meanwhile, elevated ten kinds based validation database. Conclusion results indicated that high is dramatically correlated unfavorable cancers. may served promising biomarker for malignancies.

Language: Английский

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Prognostic biomarker DARS2 correlated with immune infiltrates in bladder tumor

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 17, 2024

Background DARS2 is a pivotal member of the Aminoacyl-tRNA synthetases family that critical for regulating protein translation. However, biological role in bladder cancer remains elusive. Methods We analyzed correlation between expression and prognosis, tumor stage, immune infiltration using The Cancer Genome Atlas (TCGA) database. validated findings clinical samples from First Affiliated Hospital Nanchang University explored functions cell animal models. Results found to be upregulated cancer, associated with progression poor prognosis. Immune analysis suggested may facilitate evasion by modulating PD-L1. Cell experiments knockdown overexpress can inhibit or increase proliferation, metastasis, tumorigenesis, escape, PD-L1 levels. Conclusions Our study reveals as potential prognostic biomarker immunotherapy target BLCA.

Language: Английский

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Multiomics integration unravels genotype‐microbiome interactions shaping the conjunctival transcriptome

iMetaOmics., Journal Year: 2024, Volume and Issue: 1(2)

Published: Oct. 14, 2024

Abstract Gene expression is a molecular phenotype shaped by the interplay between genotype and environment. The microbiome represents critical environmental exposure for host. However, genotype‐microbiome interactions (GMIs) shaping host transcriptome remain largely unexplored. Here, we integrated conjunctival multiomics data from 120 pairs of twins to investigate GMIs. We identified 272,972 quantitative trait loci associated with 5946 genes 241,073 genotype‐controlled correlations gene microbial abundance. developed modeling approach, MicroGenix, that screens GMIs genome, transcriptome, identifies disease through gene‐based association tests. applied MicroGenix set found incorporating into prediction models significantly increased accuracy. accuracy were overrepresented those encoding cell adhesion molecules. further used predict metagenomes ocular surface disease. Our work provides resource studying host‐microbiome at conjunctiva computational approach using data.

Language: Английский

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MFAP3L predicts tumor microenvironment status, molecular subtypes and clinical benefit in patients with bladder cancer

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 3, 2024

Bladder cancer (BLCA), ranking as the tenth most prevalent malignancy globally, imposes a substantial public health and socio-economic challenge. Despite ongoing efforts by urologists to identify novel molecular subtypes treatment paradigms, intrinsic heterogeneity of BLCA continues obstruct efficacy current diagnostic therapeutic evaluations, leaving gap in comprehensive management BLCA. This necessitates an in-depth investigation into tumor microenvironment (TME) pivotal molecules like MFAP3L. Our research concentrated on MFAP3L, commencing with pan-cancer analysis its immune profile. We discovered that MFAP3L exhibits significant negative correlation numerous components markers BLCA, trend not observed other types. Within TCGA-BLCA cohort, patients were classified High-MFAP3L Low-MFAP3L groups according their transcript levels. exploration TME delved infiltration, subtype patterns, preferences within these groups. High expression was linked favorable prognoses, luminal subtypes, low inversely associated various characteristics. Additionally, high expressors exhibited diminished checkpoint levels, suggesting enhanced immunotherapy tolerance sensitivity oncogenic pathway targeting. Conversely, correlated poor outcomes, basal increased heightened gene mutation rates, alongside radiotherapy, EGFR-targeted treatments, immunotherapy. Hence, emerges critical yet underexplored offering insights status aiding subtyping decision-making.

Language: Английский

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