Cuproptosis Depicts Immunophenotype and Predicts Immunotherapy Response in Lung Adenocarcinoma DOI Open Access

Wolong Zhou,

Yuanda Cheng,

Linfeng Li

et al.

Journal of Personalized Medicine, Journal Year: 2023, Volume and Issue: 13(3), P. 482 - 482

Published: March 8, 2023

Although significant progress has been made in immunotherapy for lung adenocarcinoma (LUAD), there is an urgent need to identify effective indicators screen patients who are suitable immunotherapy. Systematically investigating the cuproptosis-related genes (CRGs) LUAD may provide new ideas patients' stratification. We comprehensively analyzed landscape of 12 CRGs a merged TCGA and GEO cohort. investigated associations between tumor microenvironment immunophenotypes. utilized risk score predict prognosis response individual patient. Additionally, we conducted CCK-8 experiments evaluate impact DLGAP5 knockdown on A549 cell proliferation. integrative approach analyze differentially expressed (DEGs) samples, resulting identification two distinct CRG clusters gene clusters. Based these clusters, generated immunophenotypes observed that inflamed phenotype had most abundant immune infiltrations, while desert showed poorest infiltrations. then developed model patient prediction. Patients low-risk group higher scores ESTIMATE scores, indicating active state with richer infiltrations expression checkpoint genes. Moreover, exhibited better according IPS, TIDE Imvigor210 cohort validation results. In addition, our vitro wet demonstrated could suppress proliferation A549. Novel cuproptosis molecular patterns reflected patients. The might pave way stratify response.

Language: Английский

Cuproptosis: molecular mechanisms, cancer prognosis, and therapeutic applications DOI Creative Commons
Y. Cong, Na Li, Zixin Zhang

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 22, 2025

Cuproptosis differs from other forms of cell death, such as apoptosis, necroptosis, and ferroptosis, in its unique molecular mechanisms signaling pathways. In this review, we delve into the cellular metabolic pathways copper, highlighting role copper biomolecule synthesis, mitochondrial respiration, antioxidant defense. Furthermore, elucidate relationship between cuproptosis-related genes (CRGs) cancer prognosis, analyzing their expression patterns across various tumor types impact on patient outcomes. Our review also uncovers potential therapeutic applications chelators, ionophores, copper-based nanomaterials oncology. addition, discuss emerging cuproptosis remodeling microenvironment, enhancing immune infiltration, converting "cold tumors" "hot that respond better to immunotherapy. short, underscores pivotal importance biology highlights translational a novel target.

Language: Английский

Citations

7
Identification and integration analysis of a novel prognostic signature associated with cuproptosis-related ferroptosis genes and relevant lncRNA regulatory axis in lung adenocarcinoma DOI Creative Commons
Tianyue Wang, Xinyu Jiang, Ying Lü

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: March 3, 2023

Lung adenocarcinoma (LUAD) is a highly prevalent malignancy worldwide, and its clinical prognosis assessment treatment major research direction. Both ferroptosis cuproptosis are novel forms of cell death considered to be important factors involved in cancer progression. To further understand the correlation between cuproptosis-related genes (CRFGs) LUAD, we explore molecular mechanisms related development disease. We constructed prognostic signature containing 13 CRFGs, which, after grouping based on risk score, revealed that LUAD high-risk group exhibited poor prognosis. Nomogram confirmed it could an independent factor for ROC curves DCA validated validity model. Further analysis showed three biomarkers (LIFR, CAV1, TFAP2A) were significantly correlated with immunization. Meanwhile, found LINC00324/miR-200c-3p/TFAP2A regulatory axis progression LUAD. In conclusion, our report reveals CRFGs well provide new ideas construction tools, immunotherapy, targeted therapy

Language: Английский

Citations

26
Mechanisms of cuproptosis and its relevance to distinct diseases DOI

Qiao-mei Lou,

Feifan Lai,

Jingwei Li

et al.

APOPTOSIS, Journal Year: 2024, Volume and Issue: 29(7-8), P. 981 - 1006

Published: June 2, 2024

Language: Английский

Citations

12
Clinical features and molecular landscape of cuproptosis signature‐related molecular subtype in gastric cancer DOI Creative Commons
Wei Chong,

Huicheng Ren,

Hao Chen

et al.

iMeta, Journal Year: 2024, Volume and Issue: 3(3)

Published: April 5, 2024

Abstract Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether signaling also has potential impacts on tumor initiation prognosis gastric cancer (GC). In this study, 16 cuproptosis‐related genes (CRGs) transcriptional profiles were harnessed to perform regularized latent variable model‐based clustering GC. A signature risk scoring (CSRS) scheme, based a weighted sum principle components CRGs, was used evaluate individual tumors Four distinct signature‐based clusters, characterized by differential expression patterns identified among 1136 GC samples across three independent databases. The four clusters associated with different clinical outcomes immune contexture. Based CSRS, patients can be divided into CSRS‐High CSRS‐Low subtypes. We found that DBT, MTF1 , ATP7A significantly elevated subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD PDHA1 increased subtype. Patients score prolonged survival time. Further analysis indicated correlated greater mutation burden (TMB) higher rates mutated (SMG) addition, subtype harbored more amplified focal regions related tumorigenesis ( 3q27.1, 12p12.1, 11q13.3 etc.) than tumors. Drug sensitivity analyses revealed compounds for treatment score, which experimentally validated using cells. This study highlights subtyping is features molecular landscape Quantitative evaluation CSRS will strengthen our understanding development progress

Language: Английский

Citations

5
The biological significance of cuproptosis-key gene MTF1 in pan-cancer and its inhibitory effects on ROS-mediated cell death of liver hepatocellular carcinoma DOI Creative Commons
Liying Song, Rong Zeng, Keda Yang

et al.

Discover Oncology, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 28, 2023

Metal regulatory transcription factor 1 (MTF1) has been reported to be correlated with several human diseases, especially like cancers. Exploring the underlying mechanisms and biological functions of MTF1 could provide novel strategies for clinical diagnosis therapy In this study, we conducted comprehensive analysis evaluate profiles in pan-cancer. For example, TIMER2.0, TNMplot GEPIA2.0 were employed analyze expression values The methylation levels evaluated via UALCAN DiseaseMeth version 2.0 databases. mutation pan-cancers analyzed using cBioPortal. GEPIA2.0, Kaplan-Meier plotter cBioPortal also used explore roles cancer prognosis. We found that high was related poor prognosis liver hepatocellular carcinoma (LIHC) brain lower grade glioma (LGG). Also, level associated good kidney renal clear cell (KIRC), lung cancer, ovarian breast cancer. investigated genetic alteration between primary tumor normal tissues. relationship immune cells analyzed, including T CD8 + dendritic (DC). Mechanically, MTF1-interacted molecules might participate regulation metabolism-related pathways, such as peptidyl-serine phosphorylation, negative cellular amide metabolic process peptidyl-threonine phosphorylation. Single sequencing indicated angiogenesis, DNA repair invasion. addition, vitro experiment knockdown resulted suppressed proliferation, increased reactive oxygen species (ROS) promoted death LIHC HepG2 Huh7. Taken together, pan-cancer implicated play an essential role progression various

Language: Английский

Citations

12
Machine learning screening for Parkinson’s disease-related cuproptosis-related typing development and validation and exploration of personalized drugs for cuproptosis genes DOI Open Access
Ji Wu,

Chengjian Qin,

Yuankun Cai

et al.

Annals of Translational Medicine, Journal Year: 2023, Volume and Issue: 11(1), P. 11 - 11

Published: Jan. 1, 2023

Parkinson's disease (PD) is a common, degenerative of the nervous system that characterized by death dopaminergic neurons in substantia nigra densa (SNpc). There growing evidence copper (Cu) involved myelin formation and cell through modulation synaptic activity as well neurotrophic factor-induced excitotoxicity.This study aimed to explore potential cuproptosis-related genes (CRGs) immune infiltration patterns PD development Cu chelators relevant for treatment. The datasets GSE7621, GSE20141, GSE49036 were downloaded from Gene Expression Omnibus (GEO) database. consensus clustering method was used classify specimens PD. Using weighted gene co-expression network analysis (WGCNA) random forest (RF) tree model, support vector machine (SVM) learning extreme gradient boosting (XGBoost) general linear model (GLM) algorithms screen progression-related models, column charts created verify accuracy these CRGs predicting progression. Single sample genomic enrichment (ssGSEA) estimate correlation between associated with poisoning cells function. Molecular docking interactions chelating agents cuproptosis treatment.Through ssGSEA, we identified three related ATP7A, NFE2L2 MTF1, which are We also verified LAGASCATRIOL can bind molecular docking. Consistent cluster two subtypes, among C2 subtype just enriched And more accurately diagnose progression, patients benefit feature map based on genes.CRGs such NFE2L2, ATP7B be pathogenesis provide possible new direction treatment PD, needs further in-depth study.

Language: Английский

Citations

10
Identification and validation of a novel cuproptosis-related stemness signature to predict prognosis and immune landscape in lung adenocarcinoma by integrating single-cell and bulk RNA-sequencing DOI Creative Commons
Jia Yang,

Kaile Liu,

Yang Lü

et al.

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

Published: May 23, 2023

Background Cancer stem cells (CSCs) play vital roles in lung adenocarcinoma (LUAD) recurrence, metastasis, and drug resistance. Cuproptosis has provided a novel insight into the treatment of CSCs. However, there is lack knowledge regarding cuproptosis-related genes combined with stemness signature their prognosis immune landscape LUAD. Methods Cuproptosis-related (CRSGs) were identified by integrating single-cell bulk RNA-sequencing data LUAD patients. Subsequently, subtypes classified using consensus clustering analysis, prognostic was constructed univariate least absolute shrinkage operator (LASSO) Cox regression. The association between infiltration, immunotherapy, features also investigated. Finally, expression CRSGs functional target gene validated vitro . Results We six that mainly expressed epithelial myeloid cells. Three distinct associated infiltration immunotherapy response. Furthermore, to predict overall survival (OS) patients based on eight differently (DEGs) (KLF4, SCGB3A1, COL1A1, SPP1, C4BPA, TSPAN7, CAV2, CTHRC1) confirmed validation cohorts. developed an accurate nomogram improve clinical applicability. Patients high-risk group showed worse OS lower levels cell higher features. Ultimately, further cellular experiments performed verify DEGs demonstrate SPP1 could affect proliferation, migration, Conclusion This study can be used patients, potential therapeutic targets for CSCs future.

Language: Английский

Citations

9
Dual identity of tumor-associated macrophage in regulated cell death and oncotherapy DOI Creative Commons
Yingying Shao, Yu Wang,

Ranran Su

et al.

Heliyon, Journal Year: 2023, Volume and Issue: 9(7), P. e17582 - e17582

Published: June 26, 2023

Tumor-associated macrophage (TAM) affects the intrinsic properties of tumor cells and microenvironment (TME), which can stimulate cell proliferation, migration, genetic instability, diversity includes tumors with different functional characteristics. Macrophages are now a central drug target in various diseases, especially TME, which, as "tumor promoters" "immunosuppressors", have responsibilities during development accompany by significant dynamic alterations subpopulations. Remodelling immunosuppression TME promotion pre-existing antitumor immune responses is critical altering TAM polarization, relevant to efficacy immunotherapy, uncovering exact mechanism action TAMs identifying their specific targets vital optimizing current immunotherapies. Hence, this review aims reveal triadic interactions macrophages programmed death oncotherapy, integrate certain relationships cancer treatment.

Language: Английский

Citations

4
Elucidating the evolving role of cuproptosis in breast cancer progression DOI Creative Commons
Zhanyong Zhu,

Keyu Zhu,

Jun Zhang

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(12), P. 4872 - 4887

Published: Jan. 1, 2024

Breast cancer (BC) persists as a highly prevalent malignancy in females, characterized by diverse molecular signatures and necessitating personalized therapeutic approaches. The equilibrium of copper within the organism is meticulously maintained through regulated absorption, distribution, elimination, underpinning not only cellular but also various essential biological functions. process cuproptosis initiated copper's interaction with lipoylases tricarboxylic acid (TCA) cycle, which triggers conglomeration lipoylated proteins diminishes integrity Fe-S clusters, culminating cell demise proteotoxic stress. In BC, aberrations are prominent represent crucial incident that contributes to disease progression. It influences BC metabolism affects critical traits such proliferation, invasiveness, resistance chemotherapy. Therapeutic strategies target have shown promising antitumor efficacy. Moreover, plethora cuproptosis-centric genes, including cuproptosis-related genes (CRGs), CRG-associated non-coding RNAs (ncRNAs), cuproptosis-associated regulators, been identified, offering potential for development risk assessment models or diagnostic signatures. this review, we provide comprehensive exposition fundamental principles cuproptosis, its influence on malignant phenotypes prognostic implications cuproptosis-based markers, substantial prospects exploiting therapy, thereby laying theoretical foundation targeted interventions domain.

Language: Английский

Citations

1
Characterization and authentication of anoikis signature forecast clinical features, TMB mutations and immune-filtration in lung adenocarcinoma DOI Creative Commons

Shengzhe An,

Ziwei Xu, Junjie Ma

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 25, 2024

Abstract Background Ongoing research has underlined the significant biological dimensions of anoikis in carcinogenicity and progression multiple tumors. However, there is no definitive role for prognosis lung adenocarcinoma (LUAD) tumor microenvironment (TME). Methods In this study, we employed ssGSEA to construct scores 273 genes screened 184 anoikis-associated by WGCNA single-cell sequencing. The LASSO algorithm configured LUAD prognostic risk cohort, CIBERSORT assessed differences infiltration abundance 22 immune cells. TIDE calculated discrimination based on cohort therapy variation. Finally, value two models was evaluated separately machine learning algorithms. Results anoikis-related gene score (ARGS), which classified into high ARGS low patients. Single-cell sequencing verified distribution different cellular taxa constructed a set predict differential ARGS. performed validate cell populations predictive ARGS, Risk developed LOX, MSX1, FSTL3, STEAP1, PMEPA1, SNAI1, ABCA6, PLOD2, SEMA3A, FRMD6. Further validation Gene Expression Omnibus (GEO) dataset. mesenchymal were generated an estimation patients from Cancer Genome Atlas (TCGA) database relationship between higher lower-risk groups model. Higher also negatively associated with B cells, CD4 + T other stromal or Mutations occurred more frequently high-risk group. These mutations may be changes TME suggest patient's response immunotherapy. For drug sensitivity analysis, group had lower IC50 some chemotherapeutic agents targeted agents, suggesting that sensitive these agents. Conclusion This study reinforces patterns are significantly diversity complexity TME. Quantitative assessment modification will reinforce our insights characteristics catalyze effective immunotherapeutic strategies.

Language: Английский

Citations

0