Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18
Abstract Background Protein palmitoylation is a reversible post-translational modification that increases protein hydrophobicity, which can affect protein localization, stability, and function. Although palmitoylation is frequently observed in various cancers, the specific mechanisms by which it inf...
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| Language: | English |
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BMC
2025-06-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03882-z |
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| author | Wei Xu Xiao-chao Chen Yang Wang Jian-chun Chen Zhi-jun Cao Ru Huang Chao Chen Dao-rong Hou Min-jun Jiang Chen Xu |
| author_facet | Wei Xu Xiao-chao Chen Yang Wang Jian-chun Chen Zhi-jun Cao Ru Huang Chao Chen Dao-rong Hou Min-jun Jiang Chen Xu |
| author_sort | Wei Xu |
| collection | DOAJ |
| description | Abstract Background Protein palmitoylation is a reversible post-translational modification that increases protein hydrophobicity, which can affect protein localization, stability, and function. Although palmitoylation is frequently observed in various cancers, the specific mechanisms by which it influences clear cell renal cell carcinoma (ccRCC) are still not well understood. Methods This study used transcriptome expression profiles and clinical characteristics of clear cell renal cell carcinoma (ccRCC) obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Kaplan-Meier (KM) survival analysis was performed to evaluate patient survival. Consensus clustering was applied to identify tumor palmitoylation patterns. A total of 101 different machine learning methods were used to develop predictive models. Functional enrichment analyses were conducted using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Variation Analysis (GSVA). Results Of the 34 prognosis-related palmitoylation-related genes (PRGs), 29 were used to cluster patients in the TCGA-KIRC cohort, leading to the identification of four palmitoylation clusters. We developed a risk model and a nomogram based on palmitoylation scores to enhance risk classification. Functional analysis indicated that high-risk patients exhibited disrupted fatty acid metabolism. Correlation analysis identified ZDHHC18 as a potential hub gene associated with impaired fatty acid metabolism and cuproptosis. Finally, we validated the role of ZDHHC18 in ccRCC proliferation through in vitro experiments. Conclusion Our research demonstrated that PRGs play a crucial role in the development of clear cell renal cell carcinoma (ccRCC). A nomogram based on palmitoylation scores may accurately predict the prognosis of ccRCC patients. Furthermore, the palmitoylation regulator ZDHHC18 affects cuproptosis in ccRCC, which in turn impacts patient survival. |
| format | Article |
| id | doaj-art-16748e2a943e45318a06c5b2b351b07e |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-16748e2a943e45318a06c5b2b351b07e2025-08-20T03:31:45ZengBMCCancer Cell International1475-28672025-06-0125111610.1186/s12935-025-03882-zPalmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18Wei Xu0Xiao-chao Chen1Yang Wang2Jian-chun Chen3Zhi-jun Cao4Ru Huang5Chao Chen6Dao-rong Hou7Min-jun Jiang8Chen Xu9Department of Emergency, Suzhou Ninth Hospital Affiliated to Soochow UniversityDepartment of Urology, Changhai Hospital, Naval Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Urology, Suzhou Ninth Hospital Affiliated to Soochow UniversityDepartment of Urology, Suzhou Ninth Hospital Affiliated to Soochow UniversityDepartment of Urology, Suzhou Ninth Hospital Affiliated to Soochow UniversityDepartment of Urology, Ningbo Municipal Hospital of Traditional Chinese Medicine (TCM), Affiliated Hospital of Zhejiang Chinese Medical UniversityKey Laboratory of Model Animal Research, Animal Core Facility of Nanjing Medical University, Nanjing Medical UniversityDepartment of Urology, Suzhou Ninth Hospital Affiliated to Soochow UniversityDepartment of Urology, Suzhou Ninth Hospital Affiliated to Soochow UniversityAbstract Background Protein palmitoylation is a reversible post-translational modification that increases protein hydrophobicity, which can affect protein localization, stability, and function. Although palmitoylation is frequently observed in various cancers, the specific mechanisms by which it influences clear cell renal cell carcinoma (ccRCC) are still not well understood. Methods This study used transcriptome expression profiles and clinical characteristics of clear cell renal cell carcinoma (ccRCC) obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Kaplan-Meier (KM) survival analysis was performed to evaluate patient survival. Consensus clustering was applied to identify tumor palmitoylation patterns. A total of 101 different machine learning methods were used to develop predictive models. Functional enrichment analyses were conducted using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Variation Analysis (GSVA). Results Of the 34 prognosis-related palmitoylation-related genes (PRGs), 29 were used to cluster patients in the TCGA-KIRC cohort, leading to the identification of four palmitoylation clusters. We developed a risk model and a nomogram based on palmitoylation scores to enhance risk classification. Functional analysis indicated that high-risk patients exhibited disrupted fatty acid metabolism. Correlation analysis identified ZDHHC18 as a potential hub gene associated with impaired fatty acid metabolism and cuproptosis. Finally, we validated the role of ZDHHC18 in ccRCC proliferation through in vitro experiments. Conclusion Our research demonstrated that PRGs play a crucial role in the development of clear cell renal cell carcinoma (ccRCC). A nomogram based on palmitoylation scores may accurately predict the prognosis of ccRCC patients. Furthermore, the palmitoylation regulator ZDHHC18 affects cuproptosis in ccRCC, which in turn impacts patient survival.https://doi.org/10.1186/s12935-025-03882-zProtein s-palmitoylationCcRCCZDHHC18Cuproptosis |
| spellingShingle | Wei Xu Xiao-chao Chen Yang Wang Jian-chun Chen Zhi-jun Cao Ru Huang Chao Chen Dao-rong Hou Min-jun Jiang Chen Xu Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18 Cancer Cell International Protein s-palmitoylation CcRCC ZDHHC18 Cuproptosis |
| title | Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18 |
| title_full | Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18 |
| title_fullStr | Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18 |
| title_full_unstemmed | Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18 |
| title_short | Palmitoylation regulators drive the progression of clear cell renal cell carcinoma through Inhibition of cuproptosis: insights into the role of ZDHHC18 |
| title_sort | palmitoylation regulators drive the progression of clear cell renal cell carcinoma through inhibition of cuproptosis insights into the role of zdhhc18 |
| topic | Protein s-palmitoylation CcRCC ZDHHC18 Cuproptosis |
| url | https://doi.org/10.1186/s12935-025-03882-z |
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