Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma
Background: Cuproptosis 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 illustra...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024176311 |
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| author | Liye Wang Pan Li Shuai Gong Lina Pang Mingyu Li Chi Zhang Shengli Zhang Xiaoke Zhang Guozhong Jiang Wei He |
| author_facet | Liye Wang Pan Li Shuai Gong Lina Pang Mingyu Li Chi Zhang Shengli Zhang Xiaoke Zhang Guozhong Jiang Wei He |
| author_sort | Liye Wang |
| collection | DOAJ |
| description | Background: Cuproptosis 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. Methods: We 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. Results: A 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. Conclusions: We developed a novel risk model for CCA patients, which serves as a promising biomarker for distinguishing prognosis as well as molecular and immune characteristics. |
| format | Article |
| id | doaj-art-410dfaf2ddf74831be9ce6aa09cf50dd |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-410dfaf2ddf74831be9ce6aa09cf50dd2025-01-17T04:51:44ZengElsevierHeliyon2405-84402025-01-01111e41600Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinomaLiye Wang0Pan Li1Shuai Gong2Lina Pang3Mingyu Li4Chi Zhang5Shengli Zhang6Xiaoke Zhang7Guozhong Jiang8Wei He9Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Pathology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, ChinaDepartment of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Eastern Jianshe Road, Zhengzhou, 450052, Henan, China; Corresponding author. The First Affiliated Hospital of Zhengzhou University No.1 Eastern Jianshe Road Zhengzhou, 450052, Henan, China.Background: Cuproptosis 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. Methods: We 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. Results: A 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. Conclusions: We developed a novel risk model for CCA patients, which serves as a promising biomarker for distinguishing prognosis as well as molecular and immune characteristics.http://www.sciencedirect.com/science/article/pii/S2405844024176311CuproptosisCholangiocarcinomaMolecular subtypesPrognostic modelTumor microenvironmentDrug sensitivity |
| spellingShingle | Liye Wang Pan Li Shuai Gong Lina Pang Mingyu Li Chi Zhang Shengli Zhang Xiaoke Zhang Guozhong Jiang Wei He Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma Heliyon Cuproptosis Cholangiocarcinoma Molecular subtypes Prognostic model Tumor microenvironment Drug sensitivity |
| title | Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma |
| title_full | Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma |
| title_fullStr | Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma |
| title_full_unstemmed | Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma |
| title_short | Construction of a novel cuproptosis-related gene signature and integrative analyses in cholangiocarcinoma |
| title_sort | construction of a novel cuproptosis related gene signature and integrative analyses in cholangiocarcinoma |
| topic | Cuproptosis Cholangiocarcinoma Molecular subtypes Prognostic model Tumor microenvironment Drug sensitivity |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024176311 |
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