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中华普外科手术学杂志(电子版) ›› 2024, Vol. 18 ›› Issue (06) : 659 -662. doi: 10.3877/cma.j.issn.1674-3946.2024.06.018

论著

USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用
屈翔宇1, 张懿刚2, 李浩令1, 邱天1, 谈燚1,()   
  1. 1. 233030 安徽蚌埠,蚌埠医科大学第一附属医院肝胆外科
    2. 233099 安徽蚌埠,蚌埠医科大学附属蚌埠市第三人民医院烧伤整形外科
  • 收稿日期:2023-09-25 出版日期:2029-12-26
  • 通信作者: 谈燚

Diagnostic and prognostic role of USP24 and its co-expression of tumor metabolic genes in hepatocellular carcinoma

Xiangyu Qu1, Yigang Zhang2, Haoling Li1, Tian Qiu1, Yi Tan1,()   

  1. 1. Department of Clinical Medicine, Bengbu Medical University, Bengbu Anhui Province 233030, China
    2. Department of Burns and Plastic Surgery, The Third People’s Hospital of Bengbu Medical University, Bengbu Anhui Province 233099, China
  • Received:2023-09-25 Published:2029-12-26
  • Corresponding author: Yi Tan
  • Supported by:
    2022 Key Projects of the Education Department of Anhui Province Colleges and Universities(2022AH051416)
引用本文:

屈翔宇, 张懿刚, 李浩令, 邱天, 谈燚. USP24及其共表达肿瘤代谢基因在肝细胞癌中的诊断和预后预测作用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 659-662.

Xiangyu Qu, Yigang Zhang, Haoling Li, Tian Qiu, Yi Tan. Diagnostic and prognostic role of USP24 and its co-expression of tumor metabolic genes in hepatocellular carcinoma[J/OL]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2024, 18(06): 659-662.

目的

探讨去泛素化酶USP24及其共表达肿瘤代谢基因在肝细胞癌临床诊断和预后预测中的作用。

方法

使用TCGA-LIHC队列研究USP24在肝细胞癌中的表达情况。采用生存分析评估USP24在肝细胞癌预后中的作用。采用GSEA软件预测USP24可能调控的肿瘤代谢途径,并通过共表达分析对肿瘤代谢通路主要贡献基因进行筛选。使用差异表达分析和单因素COX分析寻找与USP24相关的肿瘤代谢预后基因,并使用LASSO-COX算法构建预后模型。采用BP神经网络、支持向量机、随机森林和XGBoost算法构建肝细胞癌诊断模型。使用R4.2.2软件进行统计学分析,两组之间的比较使用Wilcoxon检验;生存分析采用Kaplan-Meier法。P<0.05为差异有统计学意义。

结果

USP24在肝细胞癌中显著高表达,且USP24高表达组的患者生存率较低。GSEA分析显示USP24与11种肿瘤代谢途径相关。共表达分析、差异表达分析和单因素COX分析筛选出19个USP24相关肿瘤代谢预后基因,LASSO-COX算法选择8个基因用于构建预后模型。生存分析结果提示高风险组的预后较低风险组更差。训练组1年、2年、3年ROC曲线的AUC分别为0.793、0.706、0.696;验证组1年、2年、3年ROC曲线的AUC分别为0.701、0.684、0.728。肝细胞癌诊断模型中XGBoost模型具有较好的诊断能力,验证组ROC曲线的AUC为0.809。

结论

USP24与肝细胞癌预后相关,可能是通过肿瘤细胞代谢调控肝细胞癌的进展。基于8个肿瘤代谢基因构建的诊断模型和预后模型可能分别有效诊断肝细胞癌以及预测患者的预后。

Objective

To investigate the role of deubiquitination enzyme USP24 and its co-expression of tumor metabolic genes in clinical diagnosis and prognosis prediction of hepatocellular carcinoma.

Methods

The expression of USP24 in hepatocellular carcinoma was studied using the TCGA-LIHC cohort. Survival analysis was used to evaluate the role of USP24 in the prognosis of hepatocellular carcinoma. GSEA software was used to predict the possible tumor metabolic pathways regulated by USP24, and the major contributing genes of tumor metabolic pathways were screened by co-expression analysis. Differential expression analysis and univariate COX analysis were used to identify the metabolic prognostic genes associated with USP24, and the prognostic model was constructed using LASSO-COX algorithm. The diagnosis model of hepatocellular carcinoma was constructed by BP neural network, support vector machine, random forest and XGBoost algorithm. R4.2.2 software was used for statistical analysis, Wilcoxon test was used for comparison between the two groups, and Kaplan-Meier method was used for survival analysis. P<0.05 was considered statistically significant.

Results

USP24 is significantly overexpressed in hepatocellular carcinoma, and the survival rate of patients with high expression of USP24 is lower. GSEA analysis showed that USP24 was associated with 11 tumor metabolic pathways. Coexpression analysis, differential expression analysis and univariate COX analysis selected 19 USP24-related metabolic prognostic genes, and 8 genes were selected by LASSO-COX algorithm to construct prognostic model. Survival analysis results suggested that the high-risk group had a worse prognosis than the low-risk group. The AUC of 1-year, 2-year and 3-year ROC curves of the training group were 0.793, 0.706 and 0.696, respectively, while the AUC of 1-year, 2-year and 3-year ROC curves of the verification group were 0.701, 0.684 and 0.728, respectively. The XGBoost model had better diagnostic ability, and the AUC of ROC curve in the verification group was 0.809.

Conclusion

USP24 is associated with the prognosis of hepatocellular carcinoma, which may regulate the progression of hepatocellular carcinoma through tumor cell metabolism. The diagnostic model and prognostic model constructed based on 8 tumor metabolic genes may be effective in diagnosing hepatocellular carcinoma and predicting the prognosis of patients, respectively.

图1 USP24基因的表达差异与预后 注:A=USP24基因在TCGA数据库正常样本和肿瘤样本中的表达差异;B=USP24基因高表达组与低表达组的生存差异。
图2 构建肿瘤代谢风险评分预后模型 注:A=USP24共表达肿瘤代谢差异基因在HCC及其正常组织中的表达热图;B=与预后相关的19个USP24共表达肿瘤代谢基因的森林图;C=肿瘤代谢预后基因的LASSO回归系数;D=LASSO回归结果的十折交叉验证;E=TCGA-LIHC队列中OS的Kaplan-Meier曲线;G=TCGA-LIHC队列中OS的ROC曲线;F=LIRI-JP队列中OS的Kaplan-Meier曲线;H=LIRI-JP队列中OS的ROC曲线。
图3 4种HCC诊断模型的构建与验证 注:A=BP神经网络ROC曲线;B=随机森林模型ROC曲线;C=支持向量机模型ROC曲线;D=XGBoost模型ROC曲线。
[1]
Bray FLaversanne MSung H,et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin202474(3): 229-263.
[2]
Chen XZhang LHe L,et al. Potassium channels as novel molecular targets in hepatocellular carcinoma[J]. Oncology Reports202350(4): 185.
[3]
Wang QLiu JChen Z,et al. Targeting metabolic reprogramming in hepatocellular carcinoma to overcome therapeutic resistance: A comprehensive review[J]. Biomed Pharmacother2024170: 116021.
[4]
Snyder NASilva GM. Deubiquitinating enzymes(DUBs): Regulation,homeostasis,and oxidative stress response[J]. J Biol Chem2021297(3): 101077.
[5]
Liu JLeung CTLiang L,et al. Deubiquitinases in Cancers: Aspects of Proliferation,Metastasis,and Apoptosis[J]. Cancers(Basel)202214(14): 3547.
[6]
Zhi XJiang SZhang J,et al. Ubiquitin-specific peptidase 24 accelerates aerobic glycolysis and tumor progression in gastric carcinoma through stabilizing PLK1 to activate NOTCH1[J]. Cancer Sci2023114(8): 3087-3100.
[7]
He HYi LZhang B,et al. USP24-GSDMB complex promotes bladder cancer proliferation via activation of the STAT3 pathway[J]. Int J Biol Sci202117(10): 2417-2429.
[8]
Mao GLi LShan C,et al. High expression of RRM2 mediated by non-coding RNAs correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma[J]. Front Med(Lausanne)20229: 833301.
[9]
Zi LMa WZhang L,et al. Uridine Inhibits Hepatocellular Carcinoma Cell Development by Inducing Ferroptosis[J]. J Clin Med202312(10): 3552.
[10]
Wu DZhang CLiao G,et al. Targeting uridine-cytidine kinase 2 induced cell cycle arrest through dual mechanism and could improve the immune response of hepatocellular carcinoma[J]. Cell Mol Biol Lett202227(1): 105.
[11]
He RQLi JDDu XF,et al. LPCAT1 overexpression promotes the progression of hepatocellular carcinoma[J]. Cancer Cell Int202121(1): 442.
[12]
Wang JWang ZYuan J,et al. Upregulation of miR-137 Expression Suppresses Tumor Growth and Progression via Interacting with DNMT3a Through Inhibiting the PTEN/Akt Signaling in HCC[J]. Onco Targets Ther202114: 165-176.
[13]
Huang WYLiao ZBZhang JC,et al. USF2-mediated upregulation of TXNRD1 contributes to hepatocellular carcinoma progression by activating Akt/mTOR signaling[J]. Cell Death Dis202213(11): 917.
[14]
Kotowski KRosik JMachaj F,et al. Role of PFKFB3 and PFKFB4 in Cancer: Genetic Basis,Impact on Disease Development/Progression,and Potential as Therapeutic Targets[J]. Cancers(Basel)202113(4): 909.
[15]
Wang SZhou LJi N,et al. Targeting ACYP1-mediated glycolysis reverses lenvatinib resistance and restricts hepatocellular carcinoma progression[J]. Drug Resist Updat202369: 100976.
[16]
Gaur KJagtap MM. Role of Artificial Intelligence and Machine Learning in Prediction,Diagnosis,and Prognosis of Cancer[J]. Cureus202214(11): e31008.
[17]
Liu YLiang YLi Q,et al. Comprehensive analysis of circulating cell-free RNAs in blood for diagnosing non-small cell lung cancer[J]. Comput Struct Biotechnol J202321: 4238-4251.
[18]
Souza VGPForder APewarchuk ME,et al. The Complex Role of the Microbiome in Non-Small Cell Lung Cancer Development and Progression[J]. Cells202312(24): 2801.
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