Dataset Information

Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer.

ABSTRACT: Cuproptosis is a novel programmed cell death that depends on copper. The role and potential mechanism of cuproptosis-related genes (CRGs) in thyroid cancer (THCA) are still unclear. In our study, we randomly divided THCA patients from the TCGA database into a training set and a testing set. A cuproptosis-related signature consisting of six genes (SLC31A1, LIAS, DLD, MTF1, CDKN2A, and GCSH) was constructed using the training set to predict the prognosis of THCA and was verified with the testing set. All patients were classified into low- and high-risk groups according to risk score. Patients in the high-risk group had a poorer overall survival (OS) than those in the low-risk group. The area under the curve (AUC) values for 5 years, 8 years, and 10 years were 0.845, 0.885, and 0.898, respectively. The tumor immune cell infiltration and immune status were significantly higher in the low-risk group, which indicated a better response to immune checkpoint inhibitors (ICIs). The expression of six cuproptosis-related genes in our prognostic signature were verified by qRT-PCR in our THCA tissues, and the results were consistent with TCGA database. In summary, our cuproptosis-related risk signature has a good predictive ability regarding the prognosis of THCA patients. Targeting cuproptosis may be a better alternative for THCA patients.

SUBMITTER: Huang J

PROVIDER: S-EPMC10004009 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer.

Huang Jiapeng J Shi Jinyuan J Wu Pu P Sun Wei W Zhang Dalin D Wang Zhihong Z Ji Xiaoyu X Lv Chengzhou C Zhang Ting T Zhang Ping P Zhang Hao H

Journal of clinical medicine 20230303 5

Cuproptosis is a novel programmed cell death that depends on copper. The role and potential mechanism of cuproptosis-related genes (CRGs) in thyroid cancer (THCA) are still unclear. In our study, we randomly divided THCA patients from the TCGA database into a training set and a testing set. A cuproptosis-related signature consisting of six genes (SLC31A1, LIAS, DLD, MTF1, CDKN2A, and GCSH) was constructed using the training set to predict the prognosis of THCA and was verified with the testing s ...[more]

PMID: 36902801

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Project description:BackgroundCuproptosis is a unique form of cell death that is dependent on copper, which is fundamentally different from other recognized forms of cell death. However, the molecular and immune characteristics in cuproptosis-defined subgroups of cholangiocarcinoma (CCA) remain to be further illustrated.MethodsWe conducted a comprehensive investigation into the genetic and transcriptional variation, prognostic significance, and expression profiles of 16 cuproptosis-related genes (CRGs). To construct a prognostic signature based on differentially expressed genes between molecular subtypes, we employed LASSO and multivariate Cox regression analyses. We then assessed the values of this signature in prognostic prediction, immune infiltration, and therapeutic responses in CCA. The robustness of the signature was further validated in the GEO and IMvigor210 cohorts. Additionally, qRT-PCR and Western blotting (WB) were utilized to confirm the expression of the signature genes across different cell lines.ResultsA total of 16 CRGs were analyzed revealed differentially expressed, and two CRG-related clusters were identified, which displayed contrasting survival times.Then, a robust cuproptosis-related risk model was established and was an independent prognostic factor for CCA, which was further validated across two external cohorts. Low-risk patients had a better overall survival than high-risk patients. The comprehensive results showed that a low-risk score was correlated with metabolism-related pathways, high infiltration of CD8 T cells, B cells, and M1 macrophages, active immunity and less aggressive phenotypes, high chemotherapeutic sensitivity, and more benefit from immunotherapy. In contrast, a high-risk score was associated with cancer and metastasis-related pathways, high infiltration of M2 macrophages, high expression of immune checkpoint genes, suppressive immunity and more aggressive phenotypes, and less benefit from chemotherapeutic and immunotherapy. In addition, the critical CRGs were further validated through qRT-PCR and WB.ConclusionsWe developed a novel risk model for CCA patients, which serves as a promising biomarker for distinguishing prognosis as well as molecular and immune characteristics.

Project description:BackgroundCuproptosis is a newly discovered unique non-apoptotic programmed cell death distinguished from known death mechanisms like ferroptosis, pyroptosis, and necroptosis. However, the prognostic value of cuproptosis and the correlation between cuproptosis and the tumor microenvironment (TME) in lower-grade gliomas (LGGs) remain unknown.MethodsIn this study, we systematically investigated the genetic and transcriptional variation, prognostic value, and expression patterns of cuproptosis-related genes (CRGs). The CRG score was applied to quantify the cuproptosis subtypes. We then evaluated their values in the TME, prognostic prediction, and therapeutic responses in LGG. Lastly, we collected five paired LGG and matched normal adjacent tissue samples from Sun Yat-sen University Cancer Center (SYSUCC) to verify the expression of signature genes by quantitative real-time PCR (qRT-PCR) and Western blotting (WB).ResultsTwo distinct cuproptosis-related clusters were identified using consensus unsupervised clustering analysis. The correlation between multilayer CRG alterations with clinical characteristics, prognosis, and TME cell infiltration were observed. Then, a well-performed cuproptosis-related risk model (CRG score) was developed to predict LGG patients' prognosis, which was evaluated and validated in two external cohorts. We classified patients into high- and low-risk groups according to the CRG score and found that patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P<0.001). A high CRG score implies higher TME scores, more significant TME cell infiltration, and increased mutation burden. Meanwhile, the CRG score was significantly correlated with the cancer stem cell index, chemoradiotherapy sensitivity-related genes and immune checkpoint genes, and chemotherapeutic sensitivity, indicating the association with CRGs and treatment responses. Univariate and multivariate Cox regression analyses revealed that the CRG score was an independent prognostic predictor for LGG patients. Subsequently, a highly accurate predictive model was established for facilitating the clinical application of the CRG score, showing good predictive ability and calibration. Additionally, crucial CRGs were further validated by qRT-PCR and WB.ConclusionCollectively, we demonstrated a comprehensive overview of CRG profiles in LGG and established a novel risk model for LGG patients' therapy status and prognosis. Our findings highlight the potential clinical implications of CRGs, suggesting that cuproptosis may be the potential therapeutic target for patients with LGG.

Project description:Background: Cuproptosis is a newly identified unique copper-triggered modality of mitochondrial cell death, distinct from known death mechanisms such as necroptosis, pyroptosis, and ferroptosis. Multiple myeloma (MM) is a hematologic neoplasm characterized by the malignant proliferation of plasma cells. In the development of MM, almost all patients undergo a relatively benign course from monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM), which further progresses to active myeloma. However, the prognostic value of cuproptosis in MM remains unknown. Method: In this study, we systematically investigated the genetic variants, expression patterns, and prognostic value of cuproptosis-related genes (CRGs) in MM. CRG scores derived from the prognostic model were used to perform the risk stratification of MM patients. We then explored their differences in clinical characteristics and immune patterns and assessed their value in prognosis prediction and treatment response. Nomograms were also developed to improve predictive accuracy and clinical applicability. Finally, we collected MM cell lines and patient samples to validate marker gene expression by quantitative real-time PCR (qRT-PCR). Results: The evolution from MGUS and SMM to MM was also accompanied by differences in the CRG expression profile. Then, a well-performing cuproptosis-related risk model was developed to predict prognosis in MM and was validated in two external cohorts. The high-risk group exhibited higher clinical risk indicators. Cox regression analyses showed that the model was an independent prognostic predictor in MM. Patients in the high-risk group had significantly lower survival rates than those in the low-risk group (p < 0.001). Meanwhile, CRG scores were significantly correlated with immune infiltration, stemness index and immunotherapy sensitivity. We further revealed the close association between CRG scores and mitochondrial metabolism. Subsequently, the prediction nomogram showed good predictive power and calibration. Finally, the prognostic CRGs were further validated by qRT-PCR in vitro. Conclusion: CRGs were closely related to the immune pattern and self-renewal biology of cancer cells in MM. This prognostic model provided a new perspective for the risk stratification and treatment response prediction of MM patients.

Dataset Information

Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer.

Publications

Identification of a Novel Cuproptosis-Related Gene Signature and Integrative Analyses in Thyroid Cancer.

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