Prognostic and immunological role of cuproptosis-related protein FDX1 in pan-cancer

Xiao, Chen; Yang, Linhui; Jin, Liangzi; Lin, Weiguo; Zhang, Faqin; Huang, Shixin; Huang, Zhijian

doi:10.3389/fgene.2022.962028

Cited by 32 publications

(20 citation statements)

References 40 publications

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“…In addition, lower expression of the FDX1 gene was reported to be closely associated with more advanced tumor-node-metastasis stages [161]. Furthermore, lower expression of FDX1 in various cancer types has been correlated with shorter survival times [13,162,163]. Despite these findings, cuproptotic events have not been well documented in diverse cancers.…”

Section: Cuproptosis In Proliferation and Metastasismentioning

confidence: 99%

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

et al. 2022

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Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various biological activities, including the clearance of aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target for the development of cancer medications in recent years. However, because tumor cells show avoidance to apoptosis, which causes treatment resistance and recurrence, numerous studies have been devoted to alternative cancer cell mortality processes, namely necroptosis, pyroptosis, ferroptosis, and cuproptosis; these RCD modalities have been extensively studied and shown to be crucial to cancer therapy effectiveness. Furthermore, evidence suggests that tumor cells undergoing regulated death may alter the immunogenicity of the tumor microenvironment (TME) to some extent, rendering it more suitable for inhibiting cancer progression and metastasis. In addition, other types of cells and components in the TME undergo the abovementioned forms of death and induce immune attacks on tumor cells, resulting in enhanced antitumor responses. Hence, this review discusses the molecular processes and features of necroptosis, pyroptosis, ferroptosis, and cuproptosis and the effects of these novel RCD modalities on tumor cell proliferation and cancer metastasis. Importantly, it introduces the complex effects of novel forms of tumor cell death on the TME and the regulated death of other cells in the TME that affect tumor biology. It also summarizes the potential agents and nanoparticles that induce or inhibit novel RCD pathways and their therapeutic effects on cancer based on evidence from in vivo and in vitro studies and reports clinical trials in which RCD inducers have been evaluated as treatments for cancer patients. Lastly, we also summarized the impact of modulating the RCD processes on cancer drug resistance and the advantages of adding RCD modulators to cancer treatment over conventional treatments.

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Section: Cuproptosis In Proliferation and Metastasismentioning

confidence: 99%

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

et al. 2022

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“…DLD, a positive regulator of cuproptosis, enhances copper-dependent cell death, which may provide new ideas for the therapeutic action of certain cancer-targeted drugs ( Xiao et al, 2022 ). Previous studies have revealed that DLD is associated with several neurodegenerative diseases ( Yan et al, 2008 ), and DLD deficiency may lead to several fatal metabolic diseases ( Ambrus et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…The properties of tumors include biological behaviors acquired during their development, such as evasion of growth inhibitors, resistance to cell death, and achievement of replicative immortality ( Hanahan and Weinberg, 2011 ). Tumor occurrence and development are complex multifactorial processes driven by genetic variation: carcinogenesis is promoted and developed, and carcinogenic components change and induce proliferation ( Xiao et al, 2022 ). Thus, the development of more effective approaches for the early detection and treatment of tumors will help reduce cancer mortality ( Bray et al, 2018 ; Cheng et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the cuproptosis-related gene DLD across cancers: A potential prognostic and immunotherapeutic target

Yang

Guo

et al. 2023

Front. Pharmacol.

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DLD is a key gene involved in “cuproptosis,” but its roles in tumor progression and immunity remain unclear. Exploring the potential mechanisms and biological roles of DLD may provide new insights for therapeutic strategies for tumors. In the present study, we analyzed the role of DLD in a variety of tumors by using several bioinformatic tools. The results showed that compared with normal tissues, tumor tissues representing multiple cancers showed significant differential expression of DLD. High DLD expression was associated with a good prognosis in BRCA, KICH, and LUAD. Conversely, high expression levels of DLD were detrimental to patient prognosis in many other tumors, such as COAD, KIRC, and KIRP. In addition, the associations of DLD with infiltrating immune cells, genetic alterations and methylation levels across cancers were assessed. Aberrant expression of DLD was positively correlated with most infiltrating immune cells, especially neutrophils. The DLD methylation level was significantly decreased in COAD, LIHC, and LUSC but significantly increased in BRCA. DLD had the highest mutation rate (6.04%) in ESCA. In LUSC, patients with genetic alterations in DLD showed a poorer prognosis. At the single-cell level, the roles of DLD in regulating cancer-associated biological functions, such as metastasis, inflammation, and differentiation, were explored. Afterward, we further investigated whether several disease-associated genes could be correlated with DLD. GO enrichment analysis indicated that DLD-related genes were mainly associated with mitochondria-related cellular components, aerobic respiration and the tricarboxylic acid cycle. Finally, the correlations between DLD expression and immunomodulatory genes, immune checkpoints, and sensitivity to some antitumor drugs were investigated. It is worth noting that DLD expression was positively correlated with immune checkpoint genes and immunomodulatory genes in most cancers. In conclusion, this study comprehensively analyzed the differential expression, prognostic value and immune cell infiltration-related function of DLD across cancers. Our results suggest that DLD has great potential to serve as a candidate marker for pancancer prognosis and immunotherapy and may provide a new direction for cancer treatment development.

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“…Furthermore, we identi ed 5 CRGs (FDX1, LIAS, LIPT1, PDHA1, DLD) to predict the prognosis for patients with THCA, which was con rmed in vitro. FDX1, a core molecular of cuproptosis reducing Cu 2+ to Cu + , was downregulated in most kinds of cancers (43). Lipoic acid synthetase (LIAS), a key enzyme synthesizing lipoate, has been proven to be involved in several metabolic diseases, including cancer (44).…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune-related Cuproptosis Genes in the Prognosis of Thyroid Cancer

Zeng

et al. 2023

Preprint

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Background: Thyroid cancer (THCA) has gradually become the highest incidence of endocrine tumors, but its immunotherapy is still in its infancy. Cuproptosis has been reported to be closely related to various tumors. However, the mechanism of cuproptosis in THCA remains obscure. Methods: TCGA-THCA dataset was downloaded from TCGA GDC portal. We then conducted survival analysis based on the cuproptosis scores (CPs), and constructed the models of RF and LASSO. GSVA and ssGSEA was subsequently performed. CIBERSORT was used to assess immune infiltration. TIDE algorithm was used to predict the likelihood of response to immunotherapy. qRT-PCR was used to confirm the expression of cuproptosis-related differentially expressed genes (CRDEGs) in THCA cells. Results: We extracted 14 cuproptosis-related genes (CRGs) from TCGA-THCA, and 11 CRGs (SLC25A3, DLD, LIAS, ATP7B, PDHA1, SLC31A1, FDX1, DBT, GCSH, LIPT1 and DLAT) were CRDEGs. Survival analysis showed that the THCA patients with low-CPs had a relatively good prognosis. No matter which model (RF model or LASSO model) was chosen, the survival rate of high-risk group was lower in both Training dataset and Testing dataset, and 5 CRDEGs was selected as potential prognostic genes for THCA. GSVA showed that there were four differentially expressed hallmark gene sets (“APICAL_JUNCTION”, “APOPTOSIS”, “ANGIOGENESIS” and “COAGULATION” ) between high- and low-risk group in RF model and LASSO model. ssGSEA showed that pathways including glycerophospholipid metabolism, carbon metabolism and so on was differentially expressed among THCA patients with high- and low-CPs. CIBERSORT showed that the infiltrations of CD8+ T cells, Tregs, M0 Macrophages and M2 Macrophages, etc. exhibited significant differences. The scores of TIDE was higher in the high-CPs group, indicating THCA patients with high-CPs might be more likely to response immune checkpoint inhibits. qRT-PCR showed the mRNA levels of the above 5 CRDEGs were significantly downregulated in FTC-133 cells and 8505C cells. Conclusions: This study identified 5 CRDEGs (FDX1, LIAS, LIPT1, DLD and PDHA1) and some immune cells associated with THCA, suggesting the treatment feasibility combined with targeting cuproptosis and immunotherapy in THCA.

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Prognostic and immunological role of cuproptosis-related protein FDX1 in pan-cancer

Cited by 32 publications

References 40 publications

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Comprehensive analysis of the cuproptosis-related gene DLD across cancers: A potential prognostic and immunotherapeutic target

Identification of Immune-related Cuproptosis Genes in the Prognosis of Thyroid Cancer

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