Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC

Zhang, Yongfa; Wang, Longrong; Zhang, Ning; Xu, Weiqi; Zhou, Jiamin; Zhao, Yiming; Zhu, Wei; Zhang, Ti; Wang, Lu

doi:10.1007/s12072-022-10381-0

Cited by 32 publications

(29 citation statements)

References 31 publications

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“…Abnormal accumulation of intracellular copper induces a new mode of cell death, copper drooping ( Kahlson and Dixon, 2022 ). The copper homeostasis has been associated with the development and prognosis of patients with various tumors ( Feng et al, 2022 ; Huang et al, 2022 ; Lei et al, 2022 ; Li et al, 2022 ; Wang et al, 2022 ). As a copper death-related gene, LIPT1 is required for lipoylation and activation of 2-ketoacid dehydrogenases in humans ( Tort et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

Liu

Luo²,

Yan³

et al. 2022

Front. Genet.

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As a key copper homeostasis-related molecule, lipoyltransferase 1 (LIPT1) is an essential enzyme for the activation of mitochondrial 2-ketoacid dehydrogenase, participating in fatty acylation. However, the biological significances of LIPT1 in the pan-cancer are unclear. Here, we comprehensively analyzed the functional characteristics of LIPT1 in human cancers and its roles in immune response. We found that LIPT1 was down-regulated in some cancers. And LIPT1 overexpression is associated with favorable prognosis in these patients, such as breast cancer, clear cell renal cell carcinoma, ovarian cancer and gastric cancer. We also explored the mutational status and methylation levels of LIPT1 in human cancers. Gene enrichment analysis indicated that abnormally expressed LIPT1 was significantly associated with immune cells infiltration, such as B cells, CD8+ T cells and cancer-associated fibroblast cells. The result from single cell sequencing reflected the important roles of LIPT1 in the regulation of several biological behaviors of cancer cells, such as DNA damage response and cell apoptosis. Taken together, our research could provide a comprehensive overview about the significances of LIPT1 in human pan-cancer progression, prognosis and immune.

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Section: Discussionmentioning

confidence: 99%

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

Liu

Luo²,

Yan³

et al. 2022

Front. Genet.

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“…Finally, we established a nomogram incorporating the CRG Risk score and clinicopathological features to predict 1-, 3-, and 5-year OS rates of GC patients. CRG Risk score was previously reported by Jiang R et al (21) in ESCA and Wang et al (72) in HCC. A high cuproptosis-related risk score was correlated with poor survival and pro-tumor immune infiltrates in TME of HCC and ESCA.…”

Section: Discussionmentioning

confidence: 92%

“…( 21 ) in ESCA and Wang et al. ( 72 ) in HCC. A high cuproptosis-related risk score was correlated with poor survival and pro-tumor immune infiltrates in TME of HCC and ESCA.…”

Section: Discussionmentioning

confidence: 97%

Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in gastric cancer

et al. 2022

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IntroductionCuproptosis is a novel identified regulated cell death (RCD), which is correlated with the development, treatment response and prognosis of cancer. However, the potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of gastric cancer (GC) remains unknown.MethodsTranscriptome profiling, somatic mutation, somatic copy number alteration and clinical data of GC samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database to describe the alterations of CRGs from genetic and transcriptional fields. Differential, survival and univariate cox regression analyses of CRGs were carried out to investigate the role of CRGs in GC. Cuproptosis molecular subtypes were identified by using consensus unsupervised clustering analysis based on the expression profiles of CRGs, and further analyzed by GO and KEGG gene set variation analyses (GSVA). Genes in distinct molecular subtypes were also analyzed by GO and KEGG gene enrichment analyses (GSEA). Differentially expressed genes (DEGs) were screened out from distinct molecular subtypes and further analyzed by GO enrichment analysis and univariate cox regression analysis. Consensus clustering analysis of prognostic DEGs was performed to identify genomic subtypes. Next, patients were randomly categorized into the training and testing group at a ratio of 1:1. CRG Risk scoring system was constructed through logistic least absolute shrinkage and selection operator (LASSO) cox regression analysis, univariate and multivariate cox analyses in the training group and validated in the testing and combined groups. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the expression of key Risk scoring genes. Sensitivity and specificity of Risk scoring system were examined by using receiver operating characteristic (ROC) curves. pRRophetic package in R was used to investigate the therapeutic effects of drugs in high- and low- risk score group. Finally, the nomogram scoring system was developed to predict patients’ survival through incorporating the clinicopathological features and CRG Risk score.ResultsMost CRGs were up-regulated in tumor tissues and showed a relatively high mutation frequency. Survival and univariate cox regression analysis revealed that LIAS and FDX1 were significantly associated with GC patients’ survival. After consensus unsupervised clustering analysis, GC patients were classified into two cuproptosis molecular subtypes, which were significantly associated with clinical features (gender, age, grade and TNM stage), prognosis, metabolic related pathways and immune cell infiltration in TME of GC. GO enrichment analyses of 84 DEGs, obtained from distinct molecular subtypes, revealed that DEGs primarily enriched in the regulation of metabolism and intracellular/extracellular structure in GC. Univariate cox regression analysis of 84 DEGs further screened out 32 prognostic DEGs. According to the expression profiles of 32 prognostic DEGs, patients were re-classified into two gene subtypes, which were significantly associated with patients’ age, grade, T and N stage, and survival of patients. Nest, the Risk score system was constructed with moderate sensitivity and specificity. A high CRG Risk score, characterized by decreased microsatellite instability-high (MSI-H), tumor mutation burden (TMB) and cancer stem cell (CSC) index, and high stromal and immune score in TME, indicated poor survival. Four of five key Risk scoring genes expression were dysregulated in tumor compared with normal samples. Moreover, CRG Risk score was greatly related with sensitivity of multiple drugs. Finally, we established a highly accurate nomogram for promoting the clinical applicability of the CRG Risk scoring system.DiscussionOur comprehensive analysis of CRGs in GC demonstrated their potential roles in TME, clinicopathological features, and prognosis. These findings may improve our understanding of CRGs in GC and provide new perceptions for doctors to predict prognosis and develop more effective and personalized therapy strategies.

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“…Iron-sulfur cluster proteins play a key role in cuproptosis and their homeostasis is involved in cuproptosis-dependent cancer therapy. Several recent studies have shown that cuproptosis-associated genes, including iron-sulfur clusters, are potential predictors of diagnostic, prognostic, and therapeutic response in some cancers and are associated with tumor microenvironment, immune response and immunotherapy [143][144][145][146][147].…”

Section: Iron-sulfur Clusters and Cuproptosismentioning

confidence: 99%

Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer

Zhang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Iron-sulfur clusters are ancient cofactors that play crucial roles in myriad cellular functions. Recent studies have shown that iron-sulfur clusters are closely related to the mechanisms of multiple cell death modalities. In addition, numerous previous studies have demonstrated that iron-sulfur clusters play an important role in the development and treatment of cancer. This review first summarizes the close association of iron-sulfur clusters with cell death modalities such as ferroptosis, cuprotosis, PANoptosis, and apoptosis and their potential role in cancer activation and drug resistance. This review hopes to generate new cancer therapy ideas and overcome drug resistance by modulating iron-sulfur clusters.

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Development and experimental verification of a prognosis model for cuproptosis-related subtypes in HCC

Cited by 32 publications

References 31 publications

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

A pan-cancer analysis of copper homeostasis-related gene lipoyltransferase 1: Its potential biological functions and prognosis values

Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in gastric cancer

Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer

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