Xu Wei, Chen Xiao-Chao, Wang Yang, Chen Jian-Chun, Cao Zhi-Jun, Huang Ru, Chen Chao, Hou Dao-Rong, Jiang Min-Jun, Xu Chen
Department of Emergency, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, 215200, China.
Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.
Cancer Cell Int. 2025 Jun 23;25(1):230. doi: 10.1186/s12935-025-03882-z.
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.
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).
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.
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.
蛋白质棕榈酰化是一种可逆的翻译后修饰，可增加蛋白质疏水性，进而影响蛋白质的定位、稳定性和功能。尽管在各种癌症中经常观察到棕榈酰化现象，但其影响肾透明细胞癌（ccRCC）的具体机制仍未完全明确。
本研究利用从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获得的肾透明细胞癌（ccRCC）的转录组表达谱和临床特征。采用Kaplan-Meier（KM）生存分析评估患者生存率。应用一致性聚类来识别肿瘤棕榈酰化模式。共使用101种不同的机器学习方法构建预测模型。使用基因本体（GO）分析、京都基因与基因组百科全书（KEGG）通路分析和基因集变异分析（GSVA）进行功能富集分析。
在34个与预后相关的棕榈酰化相关基因（PRG）中，29个用于对TCGA-KIRC队列中的患者进行聚类，从而识别出四个棕榈酰化簇。我们基于棕榈酰化评分开发了一个风险模型和一个列线图，以加强风险分类。功能分析表明，高危患者的脂肪酸代谢受到破坏。相关性分析确定ZDHHC18是一个与脂肪酸代谢受损和铜死亡相关的潜在枢纽基因。最后，我们通过体外实验验证了ZDHHC18在ccRCC增殖中的作用。
我们的研究表明，PRG在肾透明细胞癌（ccRCC）的发生发展中起关键作用。基于棕榈酰化评分的列线图可准确预测ccRCC患者的预后。此外，棕榈酰化调节因子ZDHHC18影响ccRCC中的铜死亡，进而影响患者生存。
