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

Yang, Weiguang; Wu, Haiyang; Tong, Linjian; Wang, Yulin; Guo, Qiang; Xu, Lixia; Yan, Hua; Yin, Chengliang; Sun, Zilin

doi:10.3389/fonc.2022.1015094

Cited by 9 publications

(7 citation statements)

References 58 publications

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“…Thus, TILs could be used as biomarkers with good prognostic predictive value in a variety of tumors ( 12 , 17 ). Although some prognosis gene models of OS have been established ( 18 ), few studies have reported and developed a prognostic risk model based on TILs in OS.…”

Section: Introductionmentioning

confidence: 99%

A novel molecular signature for predicting prognosis and immunotherapy response in osteosarcoma based on tumor-infiltrating cell marker genes

et al. 2023

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BackgroundTumor infiltrating lymphocytes (TILs), the main component in the tumor microenvironment, play a critical role in the antitumor immune response. Few studies have developed a prognostic model based on TILs in osteosarcoma.MethodsScRNA-seq data was obtained from our previous research and bulk RNA transcriptome data was from TARGET database. WGCNA was used to obtain the immune-related gene modules. Subsequently, we applied LASSO regression analysis and SVM algorithm to construct a prognostic model based on TILs marker genes. What’s more, the prognostic model was verified by external datasets and experiment in vitro. ResultsEleven cell clusters and 2044 TILs marker genes were identified. WGCNA results showed that 545 TILs marker genes were the most strongly related with immune. Subsequently, a risk model including 5 genes was developed. We found that the survival rate was higher in the low-risk group and the risk model could be used as an independent prognostic factor. Meanwhile, high-risk patients had a lower abundance of immune cell infiltration and many immune checkpoint genes were highly expressed in the low-risk group. The prognostic model was also demonstrated to be a good predictive capacity in external datasets. The result of RT-qPCR indicated that these 5 genes have differential expression which accorded with the predicting outcomes.ConclusionsThis study developed a new molecular signature based on TILs marker genes, which is very effective in predicting OS prognosis and immunotherapy response.

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Section: Introductionmentioning

confidence: 99%

A novel molecular signature for predicting prognosis and immunotherapy response in osteosarcoma based on tumor-infiltrating cell marker genes

et al. 2023

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“…A current study established a prognostic model of OS base on the marker genes of tumor infiltrating lymphocytes 20 . Another study also indicated that marker gene derived from cuproptosis can be used to predict the prognosis of OS 21 . In the present, we found that DSC2 possessed a prominent prediction effect, which may provide a new target to improve the prognosis of OS.…”

Section: Discussionmentioning

confidence: 99%

Validation the role of desmocollin-2 in osteosarcoma based on single cell and bulk RNA seq and experimental analyses

Zeng,

Sun,

Man

et al. 2023

J. Cancer

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Background: The aetiology of osteosarcoma (OS) remains unclear. Desmocollin-2 (DSC2) mediates intercellular adhesion and is involved in tumour progression. Therefore, we aim to investigate the potential role of DSC2 in OS. Methods: We analyzed the expression, prognostic value and immune infiltration of DSC2 in OS via single cell and bulk RNA seq data. Besides, the expression and function of DSC2 in OS were further verified by in vitro experiment. Results: We preliminarily determined that DSC2 was high expressed in OS, which was a risk factor for survival and had a strong relationship with immune cell infiltration. What's more, in vitro experiments also demonstrated that DSC2 was high expressed in OS cells, and silencing DSC2 would suppress proliferation, migration and invasion of OS cells. Conclusions: DSC2 may serve as an oncogene, which exerts a crucial role in tumor progression, predicting prognosis and immune cell infiltration in OS.

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“…A recent study indicated that copper ionophore reduced an FDX1-dependent Fe-S cluster biogeneis ( 24 ). LIPT1 (lipoyltransferase-1) transfers lipoic acid from the H protein of the glycine cleavage system to the E2 subunit of 2-ketoacid dehydrogenase, and is involved in lipoic acid regulation LIPT1 deficiency which was demonstrated to suppress TCA cycle ( 29 , 30 ). In addition, PDHA1 (pyruvate dehydrogenase E1 component subunit alpha), PDHB (pyruvate dehydrogenase B), and CDKN2A (cyclin-dependent kinase inhibitor 2A) are involved in the formation of PDHC (pyruvate dehydrogenase complex) and may unlink glycolysis and the TCA cycle during cuproptosis ( 31 – 33 ).…”

Section: Discussionmentioning

confidence: 99%

Development and validation of cuproptosis-related genes in synovitis during osteoarthritis progress

Chang

Hu²,

Chen³

et al. 2023

Front. Immunol.

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Osteoarthritis (OA) is one of the most common refractory degenerative joint diseases worldwide. Synovitis is believed to drive joint cartilage destruction during OA pathogenesis. Cuproptosis is a novel form of copper-induced cell death. However, few studies have examined the correlations between cuproptosis-related genes (CRGs), immune infiltration, and synovitis. Therefore, we analyzed CRGs in synovitis during OA. Microarray datasets (GSE55235, GSE55457, GSE12021, GSE82107 and GSE176308) were downloaded from the Gene Expression Omnibus database. Next, we conducted differential and subtype analyses of CRGs across synovitis. Immune infiltration and correlation analyses were performed to explore the association between CRGs and immune cell abundance in synovitis. Finally, single-cell RNA-seq profiling was performed using the GSE176308 dataset to investigate the expression of CRGs in the various cell clusters. We found that the expression of five CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) was significantly increased in the OA synovium. Moreover, abundant and various types of immune cells infiltrated the synovium during OA, which was correlated with the expression of CRGs. Additionally, single-cell RNA-seq profiling revealed that the cellular composition of the synovium was complex and that their proportions varied greatly as OA progressed. The expression of CRGs differed across various cell types in the OA synovium. The current study predicted that cuproptosis may be involved in the pathogenesis of synovitis. The five screened CRGs (FDX1, LIPT1, PDHA1, PDHB, and CDKN2A) could be explored as candidate biomarkers or therapeutic targets for OA synovitis.

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

Cited by 9 publications

References 58 publications

A novel molecular signature for predicting prognosis and immunotherapy response in osteosarcoma based on tumor-infiltrating cell marker genes

A novel molecular signature for predicting prognosis and immunotherapy response in osteosarcoma based on tumor-infiltrating cell marker genes

Validation the role of desmocollin-2 in osteosarcoma based on single cell and bulk RNA seq and experimental analyses

Development and validation of cuproptosis-related genes in synovitis during osteoarthritis progress

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