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

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июнь 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

Язык: Английский

---

A Novel Disulfidptosis‐Related Risk Signature for Prognostic Prediction in Patients With Ewing Sarcoma

Journal of Orthopaedic Research®, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

ABSTRACT Ewing sarcoma (ES) is a malignant bone tumor prevalent among children and adolescents. Disulfidptosis represents novel form of cell death; however, the mechanism disulfidptosis in ES remains unclear. Our aim to explore disulfidptosis‐related prognostic signature ES. Utilizing transcriptomic clinical data ES, hub genes (DRHGs) were identified by differential gene expression analysis Least Absolute Shrinkage Selection Operator (LASSO) Cox regression analysis. A risk score model (DRRS) was constructed based on these DRHGs. The performance DRRS assessed using survival receiver operating characteristic curve Immune infiltration different subgroups correlations between antitumor reagents also analyzed. In this study, we developed feature LRPPRC (leucine rich pentatricopeptide repeat containing), IQGAP1 (IQ motif containing GTPase activating protein 1), NDUFS1 (NADH:ubiquinone oxidoreductase core subunit S1), TLN1 (talin which may serve as predictive independent factor for patients high‐risk group exhibited poorer prognosis, had higher proportion myeloid‐derived suppressor cells (MDSCs) M2 type tumor‐associated macrophages, showed heightened sensitivity some agents such nilotinib olaparib. This study first construct that predict prognosis immune response patients, thereby providing new reference understanding mechanisms guiding immunotherapy.

Язык: Английский

---

Bioinformation study of immune microenvironment characteristics of disulfidptosis-related subtypes in ovarian cancer and prognostic model construction

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 8, 2025

Ovarian cancer significantly impacts women's reproductive health and remains challenging to diagnose treat. Despite advancements in understanding DNA repair mechanisms identifying novel therapeutic targets, additional strategies are still needed. Recently, a form of cell death called disulfidptosis, which is triggered by glucose deprivation, has been linked treatment resistance changes the tumor microenvironment (TME). However, its role ovarian not well understood. Bioinformatics analysis was performed on RNA-seq data from TCGA GEO databases identify disulfidptosis-related genes cancer. Differential expression pathway enrichment were conducted, followed development prognostic model using LASSO Cox regression, validated with datasets (GSE13876, GSE26712). Clinical samples analyzed quantitative polymerase chain reaction (qPCR) immunohistochemistry (IHC) validate gene expression. This study identified subtypes demonstrated their influence (TME), immunotherapy responses, patient prognosis. Six (IFNB1, IGF2, CD40LG, IL1B, IL21, CD38) associated disulfidptosis incorporated into model. predicted outcomes externally. validation showed accuracy predicting progression-free survival platinum-based chemotherapy. Our findings highlight significant impact microenvironment, providing insights that could support clinical evaluations personalized strategies.

Язык: Английский

---

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

Frontiers in Genetics, Год журнала: 2025, Номер 15

Опубликована: Янв. 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.

Язык: Английский

---

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, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 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

Язык: Английский

---

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

Oncology Letters, Год журнала: 2025, Номер 29(4), С. 1 - 24

Опубликована: Фев. 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.

Язык: Английский

---

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

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 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.

Язык: Английский

---

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

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Май 14, 2025

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. 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. 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). Statistical subtypes CESC highlighted importance therapeutic targets. seeks enhance accuracy predictions, thereby establishing foundation for formulation personalized treatment approaches.

Язык: Английский

---

A Disulfidptosis-Related Gene Signature Associated with Prognosis and Immune Cell Infiltration in Osteosarcoma

Bioengineering, Год журнала: 2023, Номер 10(10), С. 1121 - 1121

Опубликована: Сен. 25, 2023

Osteosarcoma (OS) stands as a leading aggressive bone malignancy that primarily affects children and adolescents worldwide. A recently identified form of programmed cell death, termed Disulfidptosis, may have implications for cancer progression. Yet, its role in OS remains elusive. To elucidate this, we undertook thorough examination Disulfidptosis-related genes (DRGs) within OS. This involved parsing expression data, clinical attributes, survival metrics from the TARGET GEO databases. Our analysis unveiled pronounced association between specific DRGs, particularly MYH9 LRPPRC, outcome. Subsequent to crafted risk model nomogram, both honed precise prognostication prognosis. Intriguingly, risks associated with DRGs strongly resonated immune infiltration levels, myriad checkpoints, tethered immunotherapy, sensitivities systematic treatments. conclude, our study posits especially hold potential pivotal architects tumor milieu Moreover, they offer predictive insights into treatment responses serve reliable prognostic markers those diagnosed

Язык: Английский

---

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

Biomolecules, Год журнала: 2024, Номер 14(3), С. 266 - 266

Опубликована: Фев. 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.

Язык: Английский

---