Development and validation of prognostic index based on purine metabolism genes in patients with bladder cancer DOI Creative Commons
Zixuan Wu,

Ziqing Feng,

Hongyan Wei

et al.

Frontiers in Medicine, Journal Year: 2023, Volume and Issue: 10

Published: Sept. 14, 2023

Bladder cancer (BLCA) is a prevalent malignancy affecting the urinary system and associated with significant morbidity mortality worldwide. Dysregulation of tumor metabolic pathways closely linked to initiation proliferation BLCA. Tumor cells exhibit distinct activities compared normal cells, purine metabolism pathway, responsible for providing essential components DNA RNA synthesis, believed play crucial role. However, precise involvement Purine Metabolism Genes (PMGs) in defense mechanism against BLCA remains elusive.The integration samples from TCGA GEO datasets facilitated quantitative evaluation PMGs, offering potential insights into their predictive capabilities. Leveraging wealth information encompassing mRNAsi, gene mutations, CNV, TMB, clinical features within these further enriched analysis, augmenting its robustness reliability. Through utilization Lasso regression, prediction model was developed, enabling accurate prognostic assessments context Additionally, co-expression analysis shed light on complex relationship between expression patterns unraveling functional relevance implications BLCA.PMGs exhibited increased levels high-risk cohort patients, even absence other indicators, suggesting as markers. GSEA revealed enrichment immunological tumor-related specifically group. Furthermore, notable differences were observed immune function m6a low- groups. Several genes, including CLDN6, CES1, SOST, SPRR2A, MYBPH, CGB5, KRT1, found potentially participate oncogenic processes underlying CRTAC1 identified suppressor genes. Significant discrepancies two risk groups, highlighting molecular characteristics different outcomes. Notably, strong correlations among model, CNVs, SNPs, drug sensitivity profiles.PMGs have been implicated etiology progression bladder (BLCA). Prognostic models corresponding this aid patient exploring therapeutic targets microenvironment (TME) such PMGs cell infiltration holds promise effective management, albeit necessitating research. Moreover, identification signature presents credible alternative approach predicting BLCA, signifying burgeoning avenue targeted investigations field

Language: Английский

BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity DOI Creative Commons

Zhiyong Cai,

Jinbo Chen,

Zheng-Zheng Yu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(8)

Published: Jan. 15, 2023

Abstract To improve response rate of monotherapy immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, validated that BCAT2 shapes a noninflamed TME bladder cancer. The outcomes multiomics indicate has inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal secretion CD8 + T‐cell‐related chemokines keeps robust negative correlation with BCAT2, generating decreasing tendency T cells around from far near. Cotreatment deficiency anti‐PD‐1 antibody synergistic vivo, implying the potential Moreover, value predicting efficacy immunotherapy multiple cohorts. Together, as key molecule TME, ICB biomarker guiding precision

Language: Английский

Citations

43
Effects of Chronic Heat Stress on Growth, Apoptosis, Antioxidant Enzymes, Transcriptomic Profiles, and Immune-Related Genes of Hong Kong Catfish (Clarias fuscus) DOI Creative Commons
Yongxin Liu, Changxu Tian, Zhihua Yang

et al.

Animals, Journal Year: 2024, Volume and Issue: 14(7), P. 1006 - 1006

Published: March 26, 2024

Chronic heat stress can have detrimental effects on the survival of fish. This study aimed to investigate impact prolonged high temperatures growth, antioxidant capacity, apoptosis, and transcriptome analysis Hong Kong catfish (Clarias fuscus). By analyzing morphological statistics C. fuscus subjected chronic high-temperature for 30, 60, 90 days, it was observed that growth inhibited compared control group. The experimental group showed a significant decrease in body weight length after 60 days (p < 0.05, p 0.01). A biochemical revealed alterations activities three enzymes superoxide dismutase activity (SOD); catalase (CAT); glutathione peroxidase (GPx), malondialdehyde content (MDA), concentrations serum alkaline phosphatase (ALP); Aspartate aminotransferase (AST); alanine transaminase (ALT) liver. TUNEL staining indicated stronger apoptotic signals high-temperature-stress group, suggesting high-temperature-induced oxidative stress, leading liver tissue injury apoptosis. Transcriptome identified total 1330 DEGs, with 835 genes being upregulated 495 downregulated These may be associated immune response. findings elucidate changes under temperature provide insights into underlying response mechanisms environment.

Language: Английский

Citations

11
Understanding and overcoming resistance to immunotherapy in genitourinary cancers DOI Creative Commons

S. Evans,

Yash Jani,

Caroline S. Jansen

et al.

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

Citations

10
Current trends in sensitizing immune checkpoint inhibitors for cancer treatment DOI Creative Commons
Jing Wei, Wenke Li, Pengfei Zhang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Dec. 26, 2024

Immune checkpoint inhibitors (ICIs) have dramatically transformed the treatment landscape for various malignancies, achieving notable clinical outcomes across a wide range of indications. Despite these advances, resistance to immune blockade (ICB) remains critical challenge, characterized by variable response rates and non-durable benefits. However, growing research into complex intrinsic extrinsic characteristics tumors has advanced our understanding mechanisms behind ICI resistance, potentially improving outcomes. Additionally, robust predictive biomarkers are crucial optimizing patient selection maximizing efficacy ICBs. Recent studies emphasized that multiple rational combination strategies can overcome enhance susceptibility ICIs. These findings not only deepen tumor biology but also reveal unique action sensitizing agents, extending benefits in cancer immunotherapy. In this review, we will explore underlying ICIs, discuss significance microenvironment (TIME) biomarkers, analyze current outline alternative effectiveness including personalized

Language: Английский

Citations

8
Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma DOI Creative Commons
Richard Culliford,

Samuel Lawrence,

C. Mills

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 15, 2024

Abstract Clear cell renal carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description its genomic landscape lacking. We report whole genome sequencing 778 ccRCC patients enrolled in 100,000 Genomes Project, providing for detailed somatic mutational ccRCC. identify candidate driver genes, which as well emphasising major role epigenetic regulation highlight additional biological pathways extending opportunities therapeutic interventions. Genomic characterisation identified with divergent clinical outcome; higher number structural copy alterations associated poorer prognosis, whereas VHL mutations were independently better prognosis. The observations that T-cell infiltration overall survival and genetically predicted immune evasion not supports rationale immunotherapy. These findings should inform personalised surveillance treatment strategies patients.

Language: Английский

Citations

5
Identification and validation of SERPINE1 as a prognostic and immunological biomarker in pan-cancer and in ccRCC DOI Creative Commons

Lingqin Li,

Fan Li, Zhehao Xu

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: Aug. 23, 2023

Background:SERPINE1, a serine protease inhibitor involved in the regulation of plasminogen activation system, was recently identified as cancer-related gene. However, its clinical significance and potential mechanisms pan-cancer remain obscure. Methods: In multi-omics data from public datasets, including The Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx), online web tools were used to analyze expression SERPINE1 different cancers correlation with prognosis, genetic alteration, DNA promoter methylation, biological processes, immunoregulator levels, immune cell infiltration into tumor, tumor mutation burden (TMB), microsatellite instability (MSI), immunotherapy response drug sensitivity. Further, two single-cell databases, Tumor Immune Single-cell Hub 2 (TISCH2) CancerSEA, explore roles at level. aberrant further verified clear renal carcinoma (ccRCC) through qRT-PCR patient samples, validation independent cohorts using Gene Omnibus (GEO) database, proteomic Clinical Proteomic Analysis Consortium (CPTAC) database. Results: dysregulated enriched endothelial cells fibroblasts. Copy number amplification low methylation could be partly responsible for high expression. High associated poor prognosis 21 cancers. results gene set enrichment analysis (GSEA) indicated involvement malignancy. also several immunoregulators play an immunosuppression role. Besides, found related TMB, MSI, sensitivity drugs Finally, ccRCC performed on six GEO cohorts, CPTAC Conclusion: findings present study revealed that exhibits various types is cancer immunity malignancy, providing novel insights individualized treatment.

Language: Английский

Citations

12
TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance DOI Creative Commons
Zhi Liu, Chunyu Zhang,

Jiatong Xiao

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1966 - 1986

Published: Jan. 6, 2025

Background: Identifying biomarkers that predict immunotherapy efficacy and discovering new targets for combination therapies are critical elements improving the prognosis of bladder cancer (BLCA) patients. Methods: Firstly, we explored expression patterns TBX3 in normal pan-cancer tissues correlation between immune microenvironment using data from multiple public databases. Then, combined various techniques, including bulk RNA sequencing, single-cell high-throughput cytokine arrays, functional experiments, ProcartaPlex multiplex immunoassays TissueFAXS panoramic tissue quantification assays, to demonstrate shapes an immunosuppressive tumor (TME) BLCA. Results: We identified as a key factor associated with BLCA through systematic multi-omics analysis. found is primarily expressed malignant cells, where TBX3high cells increase secretion TGFβ1, which promotes infiltration cancer-associated fibroblasts (CAFs), thereby forming microenvironment. further demonstrated enhances TGFβ1 by binding promoter, blocking counteracts effects TBX3. Moreover, reduced cancer-killing efficiency CD8+ T decreasing proportion GZMB+ knocking down anti-PD-1 treatment increased cell CAFs vivo. also validated inverse relationship TBX3+ positive microarrays. Lastly, predicted our real-world cohort cohorts. Conclusion: In summary, progression resistance inducing microenvironment, targeting could enhance

Language: Английский

Citations

0
Cancer Cell and Cancer‐Associated Fibroblast Communication‐Mediated Molecular Subtypes Portray Non‐Inflamed Tumor Microenvironment and Guide the Precision Treatment of Bladder Cancer DOI Open Access
Shenglin Gao, Chuan Liu, Lixin Mao

et al.

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

Published: Feb. 17, 2025

Abstract Cancer‐associated fibroblasts (CAFs) drive tumor progression through restructuring of the microenvironment. This investigation aim to elucidate function molecular subtypes (MS) derived from cancer cells communication with CAFs, depicting hallmarks microenvironment and precise bladder (BLCA) treatment. The BLCA data TCGA several external sources are utilized generate a novel ligand, receptor, transcription factor (LRT) associated subtype their corresponding score (LRT score). LRT‐mediated is identified via unsupervised clustering. LRT measured by principal component analysis. Then, association clusters established MS, immunophenotypes, medical endpoints, together treatment strategies investigated. Two (A B) identified. cluster score) can precisely propose classical clinical outcomes, therapeutic strategies. Cluster B (Low represent basal inflamed phenotype specified high immunity against tumors unfavorable outcomes. Furthermore, it highly sensitive immunotherapy; however, has low sensitivity antiangiogenic targeted therapies. strong biological characteristics between cancer‐associated fibroblasts. may be useful clinician tool for developing individualized

Language: Английский

Citations

0
Senescence-specific molecular subtypes stratify the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer DOI Creative Commons

Luzhe Yan,

Haisu Liang,

Tiezheng Qi

et al.

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

Citations

0
Integrated multiomics analysis highlights the immunosuppressive role of granulin precursor positive macrophages in hepatocellular carcinoma DOI Creative Commons
Jun Li, Weizhen Huang, Junjie Kuang

et al.

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e18879 - e18879

Published: Feb. 21, 2025

It has been reported that tumor-associated macrophages (TAMs) play a complicated role in cancer occurrence and development, immune escape, checkpoint blockade (ICB) resistance. However, the of granulin precursor (GRN) highly expressed (hereafter refer to GRN + macrophages) hepatocellular carcinoma (HCC) remains poorly understood. Herein, we systematically integrated multiomics analysis human tumor tissues illustrate functional HCC. is selectively by TAMs different type cancers including HCC, was significantly associated with poor prognosis several cancer. closely correlated infiltration levels most cells, especially M2 macrophage cells various cancers. In particular, both mRNA protein expression level upregulated Compared tissue, more stroma area between HCC adjacent non-tumor tissues. High M2-polarization T-cell exhaustion communicated intratumoral CD8 T cells. Functionally, contacted which inducing exhaustion. Our study offers comprehensive understanding clinical relevance immunological indicating its potential as promising target for immunotherapeutic strategies.

Language: Английский

Citations

0