Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma
Abstract Background The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be expl...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Hereditas |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41065-023-00262-3 |
| _version_ | 1797952509781737472 |
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| author | Zhi-Cheng Zhang Yi-Fu Liu Ping Xi Ye-Chen Nie Ting Sun Bin-Bin Gong |
| author_facet | Zhi-Cheng Zhang Yi-Fu Liu Ping Xi Ye-Chen Nie Ting Sun Bin-Bin Gong |
| author_sort | Zhi-Cheng Zhang |
| collection | DOAJ |
| description | Abstract Background The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored. Methods The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein–protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database. Results CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy. Conclusions The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment. |
| first_indexed | 2024-04-10T22:47:30Z |
| format | Article |
| id | doaj.art-c22fc4602edb4109bc6a23edf6c6481c |
| institution | Directory Open Access Journal |
| issn | 1601-5223 |
| language | English |
| last_indexed | 2024-04-10T22:47:30Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj.art-c22fc4602edb4109bc6a23edf6c6481c2023-01-15T12:13:43ZengBMCHereditas1601-52232023-01-01160111310.1186/s41065-023-00262-3Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinomaZhi-Cheng Zhang0Yi-Fu Liu1Ping Xi2Ye-Chen Nie3Ting Sun4Bin-Bin Gong5Department of Urology, The First Affiliated Hospital of Nanchang UniversityDepartment of Urology, The First Affiliated Hospital of Nanchang UniversityDepartment of Urology, The First Affiliated Hospital of Nanchang UniversityDepartment of Urology, The First Affiliated Hospital of Nanchang UniversityDepartment of Urology, The First Affiliated Hospital of Nanchang UniversityDepartment of Urology, The First Affiliated Hospital of Nanchang UniversityAbstract Background The response of advanced clear cell renal cell carcinoma (ccRCC) to immunotherapy is still not durable, suggesting that the immune landscape of ccRCC still needs to be refined, especially as some molecules that have synergistic effects with immune checkpoint genes need to be explored. Methods The expression levels of CENPM and its relationship with clinicopathological features were explored using the ccRCC dataset from TCGA and GEO databases. Quantitative polymerase chain reaction (qPCR) analysis was performed to validate the expression of CENPM in renal cancer cell lines. Kaplan-Meier analysis, COX regression analysis and Nomogram construction were used to systematically evaluate the prognostic potential of CENPM in ccRCC. Besides, single gene correlation analysis, protein–protein interaction (PPI) network, genetic ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) were used to predict the biological behaviour of CENPM and the possible signalling pathways involved. Finally, a comprehensive analysis of the crosstalk between CENPM and immune features in the tumor microenvironment was performed based on the ssGSEA algorithm, the tumor immune dysfunction and exclusion (TIDE) algorithm, the TIMER2.0 database and the TISIDB database. Results CENPM was significantly upregulated in ccRCC tissues and renal cancer cell lines and was closely associated with poor clinicopathological features and prognosis. Pathway enrichment analysis revealed that CENPM may be involved in the regulation of the cell cycle in ccRCC and may have some crosstalk with the immune microenvironment in tumors. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. The ssGSEA algorithm, CIBERSOPT algorithm suggests that CENPM is associated with suppressor immune cells in ccRCC such as regulatory T cells. Furthermore, the TISIDB database provides evidence that not only CENPM is positively associated with immune checkpoint genes such as CTLA4, PDCD1, LAG3, TIGIT, but also chemokines and receptors (such as CCL5, CXCL13, CXCR3, CXCR5) may be responsible for the malignant phenotype of CENPM in ccRCC. Meanwhile, predictions based on the TIDE algorithm support that patients with high CENPM expression have a worse response to immunotherapy. Conclusions The upregulation of CENPM in ccRCC predicts a poor clinical outcome, and this malignant phenotype may be associated with its exacerbation of the immunosuppressive state in the tumor microenvironment.https://doi.org/10.1186/s41065-023-00262-3Centromere protein MClear cell renal cell carcinomaPoor prognosisImmune suppression |
| spellingShingle | Zhi-Cheng Zhang Yi-Fu Liu Ping Xi Ye-Chen Nie Ting Sun Bin-Bin Gong Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma Hereditas Centromere protein M Clear cell renal cell carcinoma Poor prognosis Immune suppression |
| title | Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma |
| title_full | Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma |
| title_fullStr | Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma |
| title_full_unstemmed | Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma |
| title_short | Upregulation of CENPM is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma |
| title_sort | upregulation of cenpm is associated with poor clinical outcome and suppression of immune profile in clear cell renal cell carcinoma |
| topic | Centromere protein M Clear cell renal cell carcinoma Poor prognosis Immune suppression |
| url | https://doi.org/10.1186/s41065-023-00262-3 |
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