Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers

Cai, Yuan; He, Qingchun; Liu, Wei; Liang, Qiuju; Peng, Bi; Li, Jianbo; Zhang, Wenqin; Kang, Fanhua; Hong, Qianhui; Yan, Yuanliang; Peng, Jinwu; Xu, Zhijie; Bai, Ning

doi:10.3389/fonc.2022.952129

Cited by 46 publications

(27 citation statements)

References 35 publications

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“…LIAS synthesized lipoic acid by introducing two sulfhydryl groups at the C6 and C8 sites of the octanoic acid moiety, deficiency of which led to neonatal epilepsy, disorder in mitochondrial energetic metabolism and elevated glycine [ 100 ]. Similarly, LIAS expression levels tend to correlate with prognosis in different patients, high LIAS expression in lung cancer was suggested to have a poor prognosis, while in KIRC and ovarian cancer it was considered to be associated with a better prognosis [ 101 ]. LIPT1catalyzed the transfer of a lipoyl group to the lysine residue of the target enzymes [ 102 ], deficiency of which will lead to Leigh disease together with a deficiency of PDC [ 103 ].In addition, cancer cells growth and invasion were prevented by knocking down the expression of the LIPT1 gene [ 104 ].…”

Section: Introductionmentioning

confidence: 99%

Cuproptosis: mechanisms and links with cancers

et al. 2023

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Cuproptosis was a copper-dependent and unique kind of cell death that was separate from existing other forms of cell death. The last decade has witnessed a considerable increase in investigations of programmed cell death, and whether copper induced cell death was an independent form of cell death has long been argued until mechanism of cuproptosis has been revealed. After that, increasing number of researchers attempted to identify the relationship between cuproptosis and the process of cancer. Thus, in this review, we systematically detailed the systemic and cellular metabolic processes of copper and the copper-related tumor signaling pathways. Moreover, we not only focus on the discovery process of cuproptosis and its mechanism, but also outline the association between cuproptosis and cancers. Finally, we further highlight the possible therapeutic direction of employing copper ion ionophores with cuproptosis-inducing functions in combination with small molecule drugs for targeted therapy to treat specific cancers.

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Section: Introductionmentioning

confidence: 99%

Cuproptosis: mechanisms and links with cancers

et al. 2023

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“…The expression of LIPT1 was positively correlated with CD8 T cells and macrophages in Uterine Corpus Endometrial Carcinoma ( 55 ). The expression of LIPT1 is associated with the infiltration of many immune cells in various cancers ( 56 ). Nevertheless, the detailed mechanism of the influences of CRGs on immune cell infiltration is unclear and deserves further exploration.…”

Section: Discussionmentioning

confidence: 99%

A cuproptosis-related genes signature associated with prognosis and immune cell infiltration in osteosarcoma

Yang

Wu²,

Tong³

et al. 2022

Front. Oncol.

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Osteosarcoma (OS) is one of the most prevalent primary bone tumors at all ages of human development. The objective of our study was to develop a model of Cuproptosis-Related Genes (CRGs) for predicting prognosis in OS patients. All datasets of OS patients were obtained from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and Gene Expression Omnibus (GEO) database. We obtained the gene set (81 CRGs) related to cuproptosis by accessing the database and previous literature. All the CRGs were analyzed by univariate COX regression, least absolute shrinkage and selection operator (LASSO) COX regression analysis to screen for CRGs associated with prognosis in OS patients. Then these CRGs were used to construct a prognostic signature, which was further verified by independent cohort (GSE21257) and clinical correlation analysis. Afterward, to identify underlying mechanisms, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used for the high-risk group by using the GSEA method. The association between the prognostic signature and 28 types of immune infiltrating cells in the tumor microenvironment was assessed. Ultimately, Lipoic Acid Synthetase (LIAS) (HR=0.632, P=0.004), Lipoyltransferase 1 (LIPT1) (HR=0.524, P=0.011), BCL2 Like 1 (BCL2L1/BCL-XL) (HR=0.593, P=0.022), and Pyruvate Dehydrogenase Kinase 1 (PDK1) (HR=0.662, P=0.025) were identified. Subsequently, they were used to calculate the risk score and build a prognostic model. In the training cohort, risk score (HR=1.878, P=0.003) could be considered as an independent prognostic factor, and OS patients with high-risk scores showed lower survival rates. Biological pathways related to substance metabolism and transport were enriched. There were significant differences in immune infiltrating cells in the tumor microenvironment. All in all, The CRGs signature is related to the tumor immune microenvironment and could be used as a credible predictor of the prognostic status in OS patients.

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“…Via PubMed, we found that these target genes play a crucial role in the prognosis and malignancy of tumors. Yuan et al showed through a comprehensive pan-cancer analysis that LIAS may have potential significance in the progression of v a r io u s c a n c e r s a n d a l s o pr e d i c t t h e e f fi c ac y o f immunotherapy in cancer patients (43). PDHB could act as regulatory targets of multiple non-coding RNAs to regulate tumor cell progression (44)(45)(46).…”

Section: Discussionmentioning

confidence: 99%

A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma

Tian

Xiang

et al. 2022

Front. Immunol.

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BackgroundNeuroblastoma (NB) is the most frequent solid tumor in pediatrics, which accounts for roughly 15% of cancer-related mortality in children. NB exhibited genetic, morphologic, and clinical heterogeneity, which limited the efficacy of available therapeutic approaches. Recently, a new term ‘cuproptosis’ has been used to denote a unique biological process triggered by the action of copper. In this instance, selectively inducing copper death is likely to successfully overcome the limitations of conventional anticancer drugs. However, there is still a gap regarding the role of cuproptosis in cancer, especially in pediatric neuroblastoma.MethodsWe characterized the specific expression of cuproptosis-related genes (CRGs) in NB samples based on publicly available mRNA expression profile data. Consensus clustering and Lasso-Cox regression analysis were applied for CRGs in three independent cohorts. ESTIMATE and Xcell algorithm was utilized to visualize TME score and immune cell subpopulations’ relative abundances. Tumor Immune Dysfunction and Exclusion (TIDE) score was used to predict tumor response to immune checkpoint inhibitors. To decipher the underlying mechanism, GSVA was applied to explore enriched pathways associated with cuproptosis signature and Connectivity map (CMap) analysis for drug exploration. Finally, qPCR verified the expression levels of risk-genes in NB cell lines. In addition, PDHA1 was screened and further validated by immunofluorescence in human clinical samples and loss-of-function assays.ResultsWe initially classified NB patients according to CRGs and identified two cuproptosis-related subtypes that were associated with prognosis and immunophenotype. After this, a cuproptosis-related prognostic model was constructed and validated by LASSO regression in three independent cohorts. This model can accurately predict prognosis, immune infiltration, and immunotherapy responses. These genes also showed differential expression in various characteristic groups of all three datasets and NB cell lines. Loss-of-function experiments indicated that PDHA1 silencing significantly suppressed the proliferation, migration, and invasion, in turn, promoted cell cycle arrest at the S phase and apoptosis of NB cells.ConclusionsTaken together, this study may shed light on new research areas for NB patients from the cuproptosis perspective.

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Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers

Cited by 46 publications

References 35 publications

Cuproptosis: mechanisms and links with cancers

Cuproptosis: mechanisms and links with cancers

A cuproptosis-related genes signature associated with prognosis and immune cell infiltration in osteosarcoma

A novel cuproptosis-related subtypes and gene signature associates with immunophenotype and predicts prognosis accurately in neuroblastoma

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