A Comprehensive Analysis of the Cuproptosis-Related Gene GCSH in Pan-Cancer with a Focus on Colorectal Cancer DOI Creative Commons
Xianwen Guo,

Rong-e Lei,

Jiao Li

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Abstract Background GCSH, a gene associated with cuproptosis, has been implicated in various cancers, although its role remains incompletely understood. This study aims to conduct comprehensive analysis of GCSH across multiple cancer types elucidate tumorigenesis. Methods expression was analyzed 33 using data from TCGA database. Associations the tumor microenvironment and prognostic value were evaluated. scRNA-seq colorectal (CRC) used assess different cell types. Clinical CRC tissues, blood samples, lines utilized for validation. Functional assays drug sensitivity tests performed further GCSH. Results varied among notably higher levels CRC. demonstrated significant correlations 22 immune cells cancers. Generally, showed negative correlation scores checkpoint genes. Prognostic revealed that outcomes adrenocortical carcinoma, hepatocellular stomach adenocarcinoma, external cohort results did not consistently support these findings. Validation clinical samples confirmed elevated indicated both cancerous within tissues compared normal tissues. pathway analyses identified key biological roles identified. Conclusions exerts multifaceted specific cancers is significantly The identifies functions suggests potential sensitivities.

Язык: Английский

Big data analysis and machine learning of the role of cuproptosis-related long non-coding RNAs (CuLncs) in the prognosis and immune landscape of ovarian cancer DOI Creative Commons

Mingqin Kuang,

Yue-Yang Liu,

Hongxi Chen

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 25, 2025

Ovarian cancer (OC) is a severe malignant tumor with significant threat to women's health, characterized by high mortality rate and poor prognosis despite conventional treatments such as cytoreductive surgery platinum-based chemotherapy. Cuproptosis, novel form of cell death triggered copper ion accumulation, has shown potential in therapy, particularly through the involvement CuLncs. This study aims identify risk signatures associated CuLncs OC, construct prognostic model, explore therapeutic drugs impact on OC behavior. We analyzed ovarian data (TCGA-OV) from TCGA database, including transcriptomic clinical 376 patients. Using Pearson correlation LASSO regression, we identified 8 signature model. Patients were categorized into high- low-risk groups based their scores. performed survival analysis, model validation, drug sensitivity vitro experiments assess model's performance functional key proliferation, invasion, migration. The demonstrated predictive power, an area under curve (AUC) 0.702 for 1-year, 0.640 3-year, 0.618 5-year survival, outperforming pathological features stage grade. High-risk patients exhibited higher Tumor Immune Dysfunction Exclusion (TIDE) scores, indicating stronger immune evasion ability. Drugs JQ12, PD-0325901, sorafenib showed reduced IC50 values high-risk group, suggesting benefits. In revealed that knockdown LINC01956, CuLnc signature, significantly inhibited migration cells (P<0.05). Our explored targets OC. findings highlight importance response, providing new insights future research applications.

Язык: Английский

Процитировано

0
Assessing the prognostic and therapeutic value of cuproptosis-related genes in colon adenocarcinoma patients DOI Creative Commons

Zhanhui Ye,

Yixian Song,

Mengqing Zhu

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Апрель 10, 2025

Colon adenocarcinoma (COAD) remains a major global health challenge with poor prognosis despite advances in treatment, underscoring the need for new biomarkers. As novel mode of cell death, cuproptosis is thought to be potentially involved development cancer. However, particularly as role cuproptosis-related genes (CRGs) COAD and therapy unclear. We analyzed RNA sequencing data from The Cancer Genome Atlas COAD, focusing on CRG expression patterns their clinicopathological correlations. Using Weighted Gene Co-expression Network Analysis (WGCNA) method, we identified gene module most strongly linked conducted functional enrichment analysis explore roles within this tumorigenesis. A prognostic risk model based four CRGs (ORC1, PTTG1, DLAT, PDHB) was developed stratify patients into high-risk low-risk groups, assessing overall survival, tumor microenvironment, mutational landscape differences. also evaluated therapeutic effects ferredoxin 1 (FDX1) elesclomol promoting HCT116 LoVo lines through various experiments, including proliferation, apoptosis assessment, mitochondrial membrane potential evaluation, DLAT lipoylation detection via Western blot. Certain showed different expressions versus normal tissues. WGCNA cuproptosis, crucial pathways like cycle regulation, citrate (TCA cycle), DNA replication. stratified high groups scores, revealing that had shorter survival distinct immune infiltration, while were more sensitive immunotherapy. Experimental results indicated FDX1 exerted an inhibitory effect its combination significantly reduced promoted apoptosis, increased lipoylation, lowered cells. findings study provided perspective research biomarkers strategies value patients, laid theoretical foundation future clinical application CRGs.

Язык: Английский

Процитировано

0
CircSpna2 attenuates cuproptosis by mediating ubiquitin ligase Keap1 to regulate the Nrf2‐Atp7b signalling axis in depression after traumatic brain injury in a mouse model DOI Creative Commons

Mengran Du,

Jiayuanyuan Fu,

Jie Zhang

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(11)

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

3
Copper homeostasis and copper-induced cell death in tumor immunity: implications for therapeutic strategies in cancer immunotherapy DOI Creative Commons

Sai‐Nan Zhang,

Qibo Huang,

Tuo Ji

и другие.

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Окт. 31, 2024

Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis critical human health, its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities metal ion regulation interact with fate. This review insights into the complex mechanisms metabolism, molecular basis cuproptosis, association cancer development. We assess role cuproptosis-related genes (CRGs) associated tumorigenesis, their importance prognostic indicators targets, impact on tumor microenvironment (TME) immune response. Ultimately, this highlights interplay between copper, immunotherapy.

Язык: Английский

Процитировано

2
Targeting cuproptosis for cancer therapy: Focus on the anti-tumor immune system DOI Creative Commons
Xuan Zhang, Xiaohong Han

Cancer Pathogenesis and Therapy, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Copper (Cu) is an indispensable micronutrient that maintains signaling pathways and biological homeostasis in almost all cell types; however, its excess affects the tricarboxylic acid cycle, causes accumulation of fatty acylated proteins, destabilization iron–sulfur cluster increases levels intracellular reactive oxygen species, leading to proteotoxic stress death. Cuproptosis, a form Cu-dependent death, differs from other types regulated death (RCD) was first reported Science 2022. Recently, RCD have been targeted cancer therapy. However, escape apoptosis tumor cells resistance treatment recurrence. Therefore, there urgent need study alternative mechanisms mortality. Compared normal patients, significant increase serum Cu ion has observed patients with tumors. Moreover, proliferation, angiogenesis, metastasis are associated cuproptosis. Thus, exploring related cuproptosis will provide new perspective for development anti-cancer drugs. Importantly, closely modulation anti-tumor immunity. The expression cuproptosis-related genes (CRGs) significantly correlated immune infiltration checkpoint programmed protein 1 (PD-1)/programmed death-ligand (PD-L1). Based on these findings, series drugs used tumor-targeted combination therapy or as synergists. elucidating role per stage microenvironment (TIME) helpful clarifying potential value specific cancers. In this review, we summarize based regulation concentration. two approaches may help researchers develop more therapies targeting pathways. focused effect TIME systematically discussed CRGs immunity considering CRG-related pathways, prognosis scoring system, immunotherapy, experiments bioinformatics prediction models, ideas anticancer

Язык: Английский

Процитировано

0
A Comprehensive Analysis of the Cuproptosis-Related Gene GCSH in Pan-Cancer with a Focus on Colorectal Cancer DOI Creative Commons
Xianwen Guo,

Rong-e Lei,

Jiao Li

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 17, 2024

Abstract Background GCSH, a gene associated with cuproptosis, has been implicated in various cancers, although its role remains incompletely understood. This study aims to conduct comprehensive analysis of GCSH across multiple cancer types elucidate tumorigenesis. Methods expression was analyzed 33 using data from TCGA database. Associations the tumor microenvironment and prognostic value were evaluated. scRNA-seq colorectal (CRC) used assess different cell types. Clinical CRC tissues, blood samples, lines utilized for validation. Functional assays drug sensitivity tests performed further GCSH. Results varied among notably higher levels CRC. demonstrated significant correlations 22 immune cells cancers. Generally, showed negative correlation scores checkpoint genes. Prognostic revealed that outcomes adrenocortical carcinoma, hepatocellular stomach adenocarcinoma, external cohort results did not consistently support these findings. Validation clinical samples confirmed elevated indicated both cancerous within tissues compared normal tissues. pathway analyses identified key biological roles identified. Conclusions exerts multifaceted specific cancers is significantly The identifies functions suggests potential sensitivities.

Язык: Английский

Процитировано

0