Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma
Abstract Background Cuproptosis is a new type of copper-induced cell death that is characterized by the aggregation of lipoylated tricarboxylic acid (TCA) cycle proteins. However, its role in hepatocellular carcinoma (HCC) remains unclear. The goal of this research is to develop a cuproptosis-relate...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Biology Direct |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13062-023-00358-w |
| _version_ | 1811166004317782016 |
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| author | Yuqiao Chen Lu Tang Wentao Huang Fakolade Hannah Abisola Youyu Zhang Gewen Zhang Lei Yao |
| author_facet | Yuqiao Chen Lu Tang Wentao Huang Fakolade Hannah Abisola Youyu Zhang Gewen Zhang Lei Yao |
| author_sort | Yuqiao Chen |
| collection | DOAJ |
| description | Abstract Background Cuproptosis is a new type of copper-induced cell death that is characterized by the aggregation of lipoylated tricarboxylic acid (TCA) cycle proteins. However, its role in hepatocellular carcinoma (HCC) remains unclear. The goal of this research is to develop a cuproptosis-related signature predicting the prognosis of HCC. Methods The cuproptosis-related genes were defined using Pearson correlation coefficients. LASSO-Cox regression analysis was used to evaluate the prognostic values of cuproptosis-related genes to construct a cuproptosis-related prognostic model. The immune microenvironment analysis was performed by “ssGSEA” to reveal the associated immune cell infiltration patterns with the cuproptosis-related genes signature. The expression levels of one of the prognostic genes PDXK were then verified in HCC samples by Western Blot and immunohistochemistry. The potential roles of target genes in cuproptosis were further explored during in-vitro experiments. Results A total of 136 cuproptosis-related genes were discovered using Pearson correlation analysis in HCC. A cuproptosis-related signature that included 5 cuproptosis-related genes (PDXK, HPN, SLC25A28, RNFT1, CLEC3B) was established in the TCGA-LIHC training cohort. TCGA validation cohort and another two external validation cohorts confirmed the robustness of the signature’s predictive value. Moreover, a nomogram using the risk score was created to best predict the survival of HCC patients. The immune microenvironment analysis revealed distinct immune infiltrations patterns between different risk groups based on the signature model. Furthermore, the upregulation of PDXK was confirmed in HCC tumor tissues in 30 clinical HCC specimens. The knockdown of PDXK reduced the proliferation, migration and invasion of HCC cells. Besides, the expression of PDXK was upregulated after the induction of cuproptosis by elesclomol–CuCL2, which could be suppressed when pretreated with a copper ion chelator. And PDXK deficiency increased the sensitivity of HCC cells to cuproptosis inducer. Conclusion Our study identified a new cuproptosis-related gene signature that could predict the prognosis of HCC patient. Besides, the upregulated PDXK could promote the proliferation and metastasis of HCC. And PDXK deficiency facilities cuproptosis in HCC. Therefore, these fundings highlighted that PDXK might serve as a potential diagnostic and therapeutic target for HCC. |
| first_indexed | 2024-04-10T15:46:25Z |
| format | Article |
| id | doaj.art-6ccebe326dd1474da3754448b0404709 |
| institution | Directory Open Access Journal |
| issn | 1745-6150 |
| language | English |
| last_indexed | 2024-04-10T15:46:25Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology Direct |
| spelling | doaj.art-6ccebe326dd1474da3754448b04047092023-02-12T12:06:30ZengBMCBiology Direct1745-61502023-02-0118111810.1186/s13062-023-00358-wIdentification of a prognostic cuproptosis-related signature in hepatocellular carcinomaYuqiao Chen0Lu Tang1Wentao Huang2Fakolade Hannah Abisola3Youyu Zhang4Gewen Zhang5Lei Yao6Department of General Surgery, Xiangya Hospital, Central South UniversityDepartment of Anesthesiology, Xiangya Hospital, Central South UniversityDepartment of Thoracic Surgery, Xiangya Hospital, Central South UniversityDepartment of Thoracic Surgery, Xiangya Hospital, Central South UniversityDepartment of Thoracic Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityDepartment of General Surgery, Xiangya Hospital, Central South UniversityAbstract Background Cuproptosis is a new type of copper-induced cell death that is characterized by the aggregation of lipoylated tricarboxylic acid (TCA) cycle proteins. However, its role in hepatocellular carcinoma (HCC) remains unclear. The goal of this research is to develop a cuproptosis-related signature predicting the prognosis of HCC. Methods The cuproptosis-related genes were defined using Pearson correlation coefficients. LASSO-Cox regression analysis was used to evaluate the prognostic values of cuproptosis-related genes to construct a cuproptosis-related prognostic model. The immune microenvironment analysis was performed by “ssGSEA” to reveal the associated immune cell infiltration patterns with the cuproptosis-related genes signature. The expression levels of one of the prognostic genes PDXK were then verified in HCC samples by Western Blot and immunohistochemistry. The potential roles of target genes in cuproptosis were further explored during in-vitro experiments. Results A total of 136 cuproptosis-related genes were discovered using Pearson correlation analysis in HCC. A cuproptosis-related signature that included 5 cuproptosis-related genes (PDXK, HPN, SLC25A28, RNFT1, CLEC3B) was established in the TCGA-LIHC training cohort. TCGA validation cohort and another two external validation cohorts confirmed the robustness of the signature’s predictive value. Moreover, a nomogram using the risk score was created to best predict the survival of HCC patients. The immune microenvironment analysis revealed distinct immune infiltrations patterns between different risk groups based on the signature model. Furthermore, the upregulation of PDXK was confirmed in HCC tumor tissues in 30 clinical HCC specimens. The knockdown of PDXK reduced the proliferation, migration and invasion of HCC cells. Besides, the expression of PDXK was upregulated after the induction of cuproptosis by elesclomol–CuCL2, which could be suppressed when pretreated with a copper ion chelator. And PDXK deficiency increased the sensitivity of HCC cells to cuproptosis inducer. Conclusion Our study identified a new cuproptosis-related gene signature that could predict the prognosis of HCC patient. Besides, the upregulated PDXK could promote the proliferation and metastasis of HCC. And PDXK deficiency facilities cuproptosis in HCC. Therefore, these fundings highlighted that PDXK might serve as a potential diagnostic and therapeutic target for HCC.https://doi.org/10.1186/s13062-023-00358-wHepatocellular carcinomaCuproptosisPrognostic signatureBioinformatic analysisPDXKMetastasis |
| spellingShingle | Yuqiao Chen Lu Tang Wentao Huang Fakolade Hannah Abisola Youyu Zhang Gewen Zhang Lei Yao Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma Biology Direct Hepatocellular carcinoma Cuproptosis Prognostic signature Bioinformatic analysis PDXK Metastasis |
| title | Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma |
| title_full | Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma |
| title_fullStr | Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma |
| title_full_unstemmed | Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma |
| title_short | Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma |
| title_sort | identification of a prognostic cuproptosis related signature in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Cuproptosis Prognostic signature Bioinformatic analysis PDXK Metastasis |
| url | https://doi.org/10.1186/s13062-023-00358-w |
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