Regulation, genomics, and clinical characteristics of cuproptosis regulators in pan-cancer

Background: Cuproptosis, a copper-dependent controlled cell death, is a novel form of cell death that differs from known cell death mechanisms; however, its overall regulation in cancer remains elusive.

Methods: Multiple open-source bioinformatic platforms were used to comprehensively elucidate the expression levels, prognostic efficiency, potential biological functions, genomic and epigenetic characteristics, immune microenvironment, and drug sensitivity of cuproptosis regulators (ATP7A, ATP7B, DLAT, DLD, FDX1, GLS, LIAS, LIPT1, MTF1, NLRP3, PDHA1, PDHB, and SLC31A1) in pan-cancer.

Results: Cuproptosis-related genes (CRGs) were upregulated in most cancers tested. In KIRC, KIRP, LGG, MESO, and PCPG, most highly expressed CRGs predicted a better prognosis but poorer prognosis in patients with ACC, LIHC, and UCEC. Pathway analysis confirmed that cuproptosis regulators were associated with the metabolism-related pathways. The expression of MTF1, NLRP3, and SLC31A1 was positively related with ImmuneScore, StromalScore, and ESTIMATEScore in almost all types of tumor, whereas ATP7B, DLAT, DLD, LIAS, PDHA1, and PDHB were significantly negatively correlated with the scores. In addition, CRGs were significantly correlated with RNA stemness score, DNA stemness score, microsatellite instability, and tumor mutational burden. The expression of ATP7A, ATP7B, LIAS, and DLAT was significantly positively correlated with the drug sensitivity of Docetaxel. ATP7A, LIAS, and FDX1 were significantly negatively correlated with the drug sensitivity of UNC0638, XMD13-2, YM201636, and KIN001-260.

Conclusions: The altered genomic and clinical characteristics of cuproptosis regulators were comprehensively elucidated, providing a preliminary basis for understanding the functions of cuproptosis in pan-cancer.

 

Comments:

The study you described investigated the expression levels, prognostic significance, biological functions, genomic and epigenetic characteristics, immune microenvironment, and drug sensitivity of several genes involved in cuproptosis, a novel form of copper-dependent cell death, in various types of cancer.

The researchers used multiple open-source bioinformatic platforms to analyze data from different cancer types. They found that cuproptosis-related genes (CRGs) were upregulated in most cancers examined. Interestingly, in some specific cancers like KIRC, KIRP, LGG, MESO, and PCPG, higher expression levels of CRGs were associated with better prognosis, while in ACC, LIHC, and UCEC, higher expression levels were associated with poorer prognosis.

Pathway analysis revealed that cuproptosis regulators were associated with metabolism-related pathways, suggesting a potential role in metabolic processes within cancer cells. The expression of certain genes (MTF1, NLRP3, and SLC31A1) involved in cuproptosis was positively correlated with immune scores, stromal scores, and ESTIMATE scores across different tumor types. On the other hand, the expression of other genes (ATP7B, DLAT, DLD, LIAS, PDHA1, and PDHB) showed a significant negative correlation with these scores, indicating potential interactions between cuproptosis regulators and the tumor microenvironment.

Furthermore, the expression of cuproptosis regulators was correlated with RNA stemness score, DNA stemness score, microsatellite instability, and tumor mutational burden, suggesting their involvement in cancer stemness and genomic instability.

Regarding drug sensitivity, the researchers found associations between the expression levels of certain cuproptosis-related genes (ATP7A, ATP7B, LIAS, DLAT, and FDX1) and the sensitivity of specific drugs, such as Docetaxel, UNC0638, XMD13-2, YM201636, and KIN001-260.

In conclusion, this study provides comprehensive insights into the altered genomic and clinical characteristics of cuproptosis regulators in different types of cancer. It offers a preliminary understanding of the potential functions of cuproptosis in pan-cancer contexts. The findings highlight the relevance of cuproptosis regulators in cancer progression, prognosis, immune response, stemness, genomic instability, and drug sensitivity, paving the way for further research and potential therapeutic strategies targeting cuproptosis in cancer treatment.

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