Development and validation of nomograms and integrated software incorporating preoperative C-reactive protein level for prognostic prediction of nonmetastatic clear cell renal cell carcinoma: Results from the International Marker Consortium for Renal Cancer (INMARC) Registry

World Journal of Urology, Journal Year: 2025, Volume and Issue: 43(1)

Published: Jan. 9, 2025

Language: Английский

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Exploring prognosis and therapeutic strategies for HBV-HCC patients based on disulfidptosis-related genes

Frontiers in Genetics, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Background Hepatocellular carcinoma (HCC) accounts for over 80% of primary liver cancers and is the third leading cause cancer-related deaths worldwide. Hepatitis B virus (HBV) infection etiological factor. Disulfidptosis a newly discovered form regulated cell death. This study aims to develop novel HBV-HCC prognostic signature related disulfidptosis explore potential therapeutic approaches through risk stratification based on disulfidptosis. Methods Transcriptomic data from patients were analyzed identify BHDRGs. A model was established validated using machine learning, with internal datasets external verification. We then performed immune infiltration analysis, tumor microenvironment (TME) immunotherapy-related analysis signature. Besides, RT-qPCR immunohistochemistry conducted. Results constructed five genes ( DLAT , STC2 POF1B S100A9 CPS1 ). corresponding nomogram developed riskScores, age, stage. Stratification by median score revealed significant correlation between TME, infiltration, immunotherapy efficacy, drug sensitivity. The results experiments indicate that expression higher in tissues compared adjacent tissues. normal Conclusion stratifies into distinct subgroups BHDRGs, establishing implications prognosis assessment, TME remodeling, personalized therapy patients.

Language: Английский

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Machine learning-based bulk RNA analysis reveals a prognostic signature of 13 cell death patterns and potential therapeutic target of SMAD3 in acute myeloid leukemia

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

Published: Feb. 15, 2025

Dysregulation or abnormality of the programmed cell death (PCD) pathway is closely related to occurrence and development many tumors, including acute myeloid leukemia (AML). Studying abnormal characteristics PCD pathway-related molecular markers can provide a basis for prognosis prediction targeted drug design in AML patients. A total 1394 genes representing 13 different pathways were examined patients healthy donors. The upregulated analyzed their ability predict overall survival (OS) individually, these prognostic subsequently combined construct PCD-related signature via an integrated approach consisting 101 models based on ten machine learning algorithms. RNA transcriptome clinical data from multiple cohorts (TCGA-AML, GSE106291, GSE146173 Beat AML) obtained develop validate model. 214 identified patients, 39 which proven be training cohort. On average C-index number model combinations, index was developed validated predicting OS. nomogram then generated index, age ELN risk stratification cohort cohort, revealing satisfactory predictive power (AUC values ≥ 0.7). With mutation patterns, higher associated with worse significantly scores immunosuppressive cells mature subtypes. As gene most expression SMAD3 further vitro. harboring KMT2A rearrangements more sensitive inhibitor SIS3, autophagy-related marker LC3 increased KMT2A-rearranged lines after SIS3 monotherapy treatment. levels have potential value used therapy AML, findings lead effective strategies treatment high-risk

Language: Английский

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BDNF is a prognostic biomarker involved in the immune infiltration of lung adenocarcinoma and associated with programmed cell death

Oncology Letters, Journal Year: 2025, Volume and Issue: 29(4), P. 1 - 24

Published: Feb. 20, 2025

It is well established that genes associated with cell death can serve as prognostic markers for patients cancer. Programmed (PCD) known to play a role in cancer apoptosis and antitumor immunity. With the continuous discovery of new forms PCD, roles PCD lung adenocarcinoma (LUAD) require ongoing evaluation. In present study, mRNA expression data clinical information 15 were extracted from publicly available databases systematically analyzed. Utilizing these data, robust risk prediction model was incorporates six PCD-related (PRGs). Datasets Gene Expression Omnibus database employed validate exhibiting risk-associated characteristics. The PRG-based reliably predicted prognosis LUAD, high-risk group showing poor prognosis, reduced levels immune infiltration molecules diminished human leukocyte antigens. Additionally, relationships among PRGs, somatic mutations, tumor stemness index assessed. Based on characteristics, nomogram constructed, patient stratification performed, small-molecule drug candidates predicted, mutations chemotherapy responses Furthermore, reverse transcription-quantitative PCR used assess PDGs vitro, critical brain-derived neurotrophic factor LUAD development identified through Mendelian randomization, gene knockdown, wound healing, western blot colony formation assays. These findings offer insights into targeted therapies particularly high BDNF expression.

Language: Английский

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Disulfidptosis, a novel regulated cell death to predict survival and therapeutic response in kidney renal clear cell carcinoma

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 22, 2025

Metabolic regulation of cell death has become a potential therapeutic target for kidney renal clear carcinoma (KIRC), which is distinguished by notable heterogeneity and significant immune infiltration. Disulfidptosis, recently identified form death, gained prominence in antitumor immunity. This research aims to investigate the correlation between disulfidptosis prognosis KIRC, while also exploring possibility predicting response disulfidptosis-associated genes (DAGs). We sourced clinical data RNA sequence KIRC from Cancer Genome Atlas Database. Employing unsupervised clustering based on 23 DAGs, we further key differentially expressed (DEGs) clusters construct DAG prognostic signature. A nomogram was developed validated predict outcome KIRC. Finally, examined infiltration, tumor mutational burden, immunotherapy response, sensitivity drugs high low-risk groups. Two distinct patient were successfully stratified using 23-DAG-related signature, comprising 11 genes. resulted robust risk model with strong predictive accuracy overall survival. The nomogram, incorporating DAG-based scores, age, pM stage, exhibited excellent performance. high-risk group displayed increased infiltration showed heightened immunotherapies targeted treatments. study established highlighting its landscape responses. Novel disulfidptosis-related biomarkers revealed profiles, drug sensitivities, potentials among patients.

Language: Английский

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Regulation of Different Types of Cell Death by Noncoding RNAs: Molecular Insights and Therapeutic Implications

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: 8(5), P. 1205 - 1226

Published: April 30, 2025

Noncoding RNAs (ncRNAs) are crucial regulatory molecules in various biological processes, despite not coding for proteins. ncRNAs further divided into long noncoding (lncRNAs), microRNAs (miRNAs), and circular (circRNAs) based on the size of their nucleotides. These play roles transcriptional, post-transcriptional, epigenetic regulation. The RNAs, including lncRNAs, miRNAs, circRNAs, essential modalities cellular death, such as apoptosis, ferroptosis, cuproptosis, pyroptosis, disulfidptosis, necroptosis. integral to modulating gene expression protein functionality during death mechanisms. In circRNAs influence transcription apoptotic genes. these target genes proteins involved iron homeostasis oxidative stress responses. For regulate pathways associated with accumulation copper ions, leading death. During modulate inflammatory mediators caspases, affecting proinflammatory cell pathway. necroptosis, oversee formation necrosomes, thereby influencing balance between survival Disulfidptosis is a unique type regulated caused by excessive disulfide bonds within cells, cytoskeletal collapse stress, especially under glucose-limited conditions. This investigation highlights complex mechanisms through which coordinate emphasizing therapeutic promise potential targets, particularly domain cancer treatment.

Language: Английский

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Immunological features of various molecular subtypes of cervical cancer and their prognostic implications in the context of disulfidptosis

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: May 14, 2025

Objective Cervical cancer ranks among the most prevalent malignancies impacting women globally. Disulfidptosis represents a recently identified pathway of cellular demise, although its role in context cervical is not well elucidated. This research investigates significance Disulfidptosis-Related Genes (DRGs) within cancer. Furthermore, it aims to analyze differences prognosis and immune infiltration different molecular subtypes. Methods We compiled genes associated with disulfidptosis from variety databases perform differential expression analysis. Subsequently, samples are grouped through consensus clustering. To evaluate cell infiltration, we employed CIBERSORT. Additionally, checkpoint (ICGs) were gathered existing literature databases, enabling statistical analyses two subtype (CESC). Following our using GO, KEGG, GSEA compare between Lastly, prognostic risk model was constructed LASSO regression validated ROC. Results study seven key genes: PCBP3, ARNT, ANP32E, DSTN, CD2AP, EPAS1 , ACTN1 .The clustering analysis showed DFS(disease-free survival) various clusters. The gene CXCL1 displayed highly significant A (Cluster 1) B 2) (CESC) samples. set enrichment negative regulation peptidase activity IL-17 signaling pathway, which link subtype-specific differentially expressed (DEGs). Conclusion Statistical subtypes CESC highlighted importance therapeutic targets. seeks enhance accuracy predictions, thereby establishing foundation for formulation personalized treatment approaches.

Language: Английский

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Disulfidptosis-related genes serve as potential prognostic biomarkers and indicate tumor microenvironment characteristics and immunotherapy response in prostate cancer

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

Published: June 19, 2024

Abstract Disulfidptosis, a newly identified programmed cell death pathway in prostate cancer (PCa), is closely associated with intracellular disulfide stress and glycolysis. This study aims to elucidate the roles of disulfidptosis-related genes (DRGs) pathogenesis progression PCa, goal improving diagnostic therapeutic approaches. We analyzed PCa datasets normal tissue transcriptome data from TCGA, GEO, MSKCC. Using consensus clustering analysis LASSO regression, we developed risk scoring model, which was validated an independent cohort. The model's predictive accuracy confirmed through Kaplan–Meier curves, receiver operating characteristic (ROC) nomograms. Additionally, explored relationship between score immune infiltration, examined tumor microenvironment somatic mutations across different groups. also investigated responses immunotherapy drug sensitivity. Our two disulfidosis subtypes significant differences survival, environments, treatment responses. According our score, high-risk group exhibited poorer progression-free survival (PFS) higher mutational burden (TMB), increased suppression. Functional enrichment linked features key pathways, including IL-17 signaling pathway. Moreover, sensitivity revealed varied chemotherapy, suggesting potential for disulfidosis-based personalized strategies. Notably, PROK1 as crucial prognostic marker its reduced expression correlating disease progression. In summary, comprehensively assessed clinical implications DRGs prognosis, offering vital insights tailored precision medicine

Language: Английский

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ALMS1-IT1: A Key Player in the Novel Disulfidptosis-Related LncRNA Prognostic Signature for Head and Neck Squamous Cell Carcinoma

Biomolecules, Journal Year: 2024, Volume and Issue: 14(3), P. 266 - 266

Published: Feb. 23, 2024

Disulfidptosis is a newly discovered form of programmed cell death that induced by disulfide stress. It closely associated with various cancers, including head and neck squamous carcinoma (HNSCC). However, the factors involved in modulation disulfidptosis-related genes (DRGs) still remain unknown. In this study, we established validated novel risk score model composed 11 lncRNAs (DRLs) based on 24 DRGs HNSCC. The results revealed strong correlations between 11-DRL prognostic signature clinicopathological features, immune infiltration, immune-related functions, disulfidptosis-associated pathways, NADPH oxidoreductase activities. Furthermore, studied verified involvement ALMS1-IT1, one DRLs, disulfidptosis HNSCC lines. A series assays demonstrated ALMS1-IT1 modulated under starvation conditions pentose phosphate pathway (PPP)-dependent manner. Knockdown inhibited PPP, contributing to decline levels, which resulted formation multiple intermolecular bonds actin cytoskeleton proteins collapse F-actin cytoplasm. Therefore, highly expressed SLC7A11high cells, can be considered promising therapeutic target for disulfidptosis-focused treatment strategies cancer other diseases.

Language: Английский

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Development of a prognostic model based on different disulfidptosis related genes typing for kidney renal clear cell carcinoma

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

Published: March 13, 2024

Background: Kidney renal clear cell carcinoma (KIRC) is a common and clinically significant subtype of kidney cancer. A potential therapeutic target in KIRC disulfidptosis, novel mode death induced by disulfide stress. The aim this study was to develop prognostic model explore the clinical significance different disulfidptosis gene typings from KIRC. Methods: comprehensive analysis chromosomal localization, expression patterns, mutational landscape, copy number variations, 10 genes conducted. Patients were categorized into distinct subtypes using Non-negative Matrix Factorization (NMF) typing method based on patterns. Weighted Gene Co-expression Network Analysis (WGCNA) used dataset identify differentially expressed between clusters. risk signature created LASSO-Cox regression validated survival analysis. An interaction score immune infiltration, tumor microenvironment characteristics pathway enrichment investigated. Results: Initial findings highlight differential specific DRGs KIRC, with genomic instability somatic mutation revealing key insights their role cancer progression. NMF clustering differentiates patients subgroups outcomes profiles, hierarchical identifies modules associated biological parameters, leading development stratification (LRP8, RNASE2, CLIP4, HAS2, SLC22A11, KCTD12) predictive infiltration drug sensitivity. Pathway further delineates molecular pathways high-risk low-risk patients, offering targets for personalized treatment. Lastly, normal cells provides mechanisms underlying highlighting biomarkers targets. Conclusion: This contributes understanding management patients. shows applicability sheds light disulfide-induced death.

Language: Английский

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