[1]宋海锋,蔡小娟,彭昆伟.基于PI3K-AKT通路基因的肝癌预后风险模型的构建和验证[J].医学信息,2025,38(03):7-15.[doi:10.3969/j.issn.1006-1959.2025.03.002]
　SONG Haifeng,CAI Xiaojuan,PENG Kunwei.Construction and Verification of a Prognostic Risk Model for Hepatocellular Carcinoma Based on PI3K-AKT Pathway Genes[J].Journal of Medical Information,2025,38(03):7-15.[doi:10.3969/j.issn.1006-1959.2025.03.002]
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基于PI3K-AKT通路基因的肝癌预后风险模型的构建和验证()
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医学信息[ISSN:1006-1959/CN:61-1278/R]

卷:
38卷
期数:
2025年03期
页码:
7-15
栏目:
生物信息学
出版日期:
2025-02-01

文章信息/Info

Title:
Construction and Verification of a Prognostic Risk Model for Hepatocellular Carcinoma Based on PI3K-AKT Pathway Genes
文章编号:
1006-1959（2025）03-0007-09
作者:
宋海锋1; 蔡小娟1; 彭昆伟2
1.连州市人民医院肿瘤科，广东 连州 513400；2.广州医科大学附属第二医院肿瘤科，广东 广州 510000
Author(s):
SONG Haifeng1;  CAI Xiaojuan1;  PENG Kunwei2
1.Department of Oncology, Lianzhou People′s Hospital, Lianzhou 513400, Guangdong, China;2.Department of Oncology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, Guangdong, China
关键词:
肝癌; 风险模型; 预后; PI3K-AKT
Keywords:
Hepatocellular carcinoma;  Risk model;  Prognostic;  PI3K-AKT
分类号:
R735.7
DOI:
10.3969/j.issn.1006-1959.2025.03.002
文献标志码:
A
摘要:
目的 利用PI3K-AKT通路相关基因，构建并验证风险评分模型评估肝癌的预后。方法 从TCGA数据库中下载肝癌患者的转录组数据和临床数据，从Genecard数据库获取PI3K-AKT信号通路相关基因，保留相关性排名前100的基因，提取PI3K-AKT通路相关基因的表达矩阵。患者按1∶1比例随机分为训练集和验证集，采用单因素Cox分析、最小绝对收缩和选择算子（LASSO）回归分析和多因素Cox分析构建预后模型，采用受试者工作特征（ROC）曲线、校正曲线和nomogram评价预后模型的预测性能。同时对风险不同的患者进行差异基因筛选，并进行功能富集分析、免疫细胞浸润分析和免疫功能分析。结果 基于PI3K-AKT信号通路共筛选出4个基因参与构建风险模型：EGF、ESR1、SPP1和RHEB。风险值计算公式：风险值=EGF×0.5139-ESR1×0.6308+SPP1×0.0754+RHEB×0.3407。患者按中位风险评分分为高危组和低危组，生存分析显示无论是在训练集还是验证集，高风险组患者的生存时间均低于低风险组患者，即使在不同的临床病理亚组中，预后模型也具有良好的预后表现，患者1、3、5年总生存的ROC曲线下面积分别为0.718、0.661、0.651。单因素和多因素Cox回归分析显示，风险评分与临床分期可作为独立预后因子。富集分析显示，差异基因主要在external encapsulating structure organization，extracellular matrix organization，extracellular structure organization等方面富集。免疫功能分析显示，TypeⅠ IFN response和TypeⅡ IFN response的免疫功能评分在低风险组更高。此外，CTLA-4和PD1表达在高风险组高表达，但PD-L1和PD-L2表达在两组中无显著差异。结论 由EGF、ESR1、SPP1和RHEB组成的风险模型可用于肝癌患者预后预测，为科学预测肝癌的预后提供新的参考依据。
Abstract:
Objective To construct and validate a risk scoring model using PI3K-AKT pathway-related genes to evaluate the prognosis of hepatocellular carcinoma. Methods Transcriptome data and clinical data of liver cancer patients were downloaded from the TCGA database. PI3K-AKT signaling pathway-related genes were obtained from the Genecard database. The top 100 genes were retained and the expression matrix of PI3K-AKT pathway-related genes was extracted. The patients were randomly divided into training set and validation set according to the ratio of 1∶1. The prognostic model was constructed by univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox analysis. The predictive performance of the prognostic model was evaluated by receiver operating characteristic (ROC) curve, calibration curve and nomogram. At the same time, differential gene screening was performed on patients with different risks, and functional enrichment analysis, immune cell infiltration analysis and immune function analysis were performed. Results Based on the PI3K-AKT signaling pathway, four genes were screened to participate in the construction of risk models: EGF, ESR1, SPP1 and RHEB. Risk value calculation formula: Risk value=EGF×0.5139-ESR1×0.6308+SPP1×0.0754+RHEB×0.3407. Patients were divided into high-risk group and low-risk group according to the median risk score. Survival analysis showed that the survival time of patients in the high-risk group was lower than that in the low-risk group, whether in the training set or the validation set. Even in different clinicopathological subgroups, the prognostic model also had good prognosticperformance. The area under the ROC curve of 1-, 3-, and 5-year overall survival was 0.718, 0.661, and 0.651, respectively. Univariate and multivariate Cox regression analysis showed that risk score and clinical stage could be used as independent prognostic factors. Enrichment analysis showed that the differential genes were mainly enriched in external concentrating structure organization, extracellular matrix organization, extracellular structure organization and so on. Immune function analysis showed that the immune function scores of Type Ⅰ IFN response and Type Ⅱ IFN response were higher in the low-risk group. In addition, CTLA-4 and PD1 were highly expressed in the high-risk group, but there was no significant difference in PD-L1 and PD-L2 expression between the two groups. Conclusion The risk model composed of EGF, ESR1, SPP1 and RHEB can be used to predict the prognosis of patients with hepatocellular carcinoma, and provide a new reference for scientifically predicting the prognosis of hepatocellular carcinoma.

参考文献/References:

[1]Sung H,Ferlay J,Siegel RL,et al.Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J].CA Cancer J Clin,2021,71(3):209-249.[2]Huang DQ,Singal AG,Kono Y,et al.Changing global epidemiology of liver cancer from 2010 to 2019: NASH is the fastest growing cause of liver cancer[J].Cell Metab,2022,34(7):969-977.e2.[3]Reveron-Thornton RF,Teng MLP,Lee EY,et al.Global and regional long-term survival following resection for HCC in the recent decade:A meta-analysis of 110 studies[J].Hepatol Commun,2022,6(7):1813-1826.[4]Brown ZJ,Tsilimigras DI,Ruff SM,et al.Management of Hepatocellular Carcinoma:A Review [J].JAMA Surg,2023,158(4):410-420.[5]Huang DQ,Singal AG,Kanwal F,et al.Hepatocellular carcinoma surveillance-utilization, barriers and the impact of changing aetiology[J].Nat Rev Gastroenterol Hepatol,2023,20(12):797-809.[6]Lawrence MS,Stojanov P,Mermel CH,et al.Discovery and saturation analysis of cancer genes across 21 tumour types[J].Nature,2014,505(7484):495-501.[7]Hennessy BT,Smith DL,Ram PT,et al.Exploiting the PI3K/AKT pathway for cancer drug discovery[J].Nat Rev Drug Discov,2005,4(12):988-1004.[8]Sun Y,Zhang H,Meng J,et al.S-palmitoylation of PCSK9 induces sorafenib resistance in liver cancer by activating the PI3K/AKT pathway[J].Cell Rep,2022,40(7):111194.[9]Zhou X,Li TM,Luo JZ,et al.CYP2C8 Suppress Proliferation, Migration, Invasion and Sorafenib Resistance of Hepatocellular Carcinoma via PI3K/Akt/p27(kip1) Axis[J].J Hepatocell Carcinoma,2021,8:1323-1338.[10]Yu L,Wei J,Liu P.Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer[J].Semin Cancer Biol,2022,85:69-94.[11]He Y,Sun MM,Zhang GG,et al.Targeting PI3K/Akt signal transduction for cancer therapy [J].Signal Transduct Target Ther,2021,6(1):425.[12]Ye L,Mayerle J,Ziesch A,et al.The PI3K inhibitor copanlisib synergizes with sorafenib to induce cell death in hepatocellular carcinoma[J].Cell Death Discov,2019,5:86.[13]Andre F,Ciruelos E,Rubovszky G,et al.Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer[J].N Engl J Med,2019,380(20):1929-1940.[14]Paskeh MDA,Ghadyani F,Hashemi M,et al.Biological impact and therapeutic perspective of targeting PI3K/Akt signaling in hepatocellular carcinoma: Promises and Challenges[J].Pharmacol Res,2023,187:106553.[15]Pan Z,Liu C,Zhi Y,et al.LIMK1 nuclear translocation promotes hepatocellular carcinoma progression by increasing p-ERK nuclear shuttling and by activating c-Myc signalling upon EGF stimulation[J].Oncogene,2021,40(14):2581-2595.[16]Xu Y,Xu H,Li M,et al.KIAA1199 promotes sorafenib tolerance and the metastasis of hepatocellular carcinoma by activating the EGF/EGFR-dependent epithelial-mesenchymal transition program[J].Cancer Lett,2019,454:78-89.[17]Liu X,Wang X,Chai B,et al.miR-199a-3p/5p regulate tumorgenesis via targeting Rheb in non-small cell lung cancer[J].Int J Biol Sci,2022,18(10):4187-4202.[18]Bao Y,Tang J,Qian Y,et al.Long noncoding RNA BFAL1 mediates enterotoxigenic Bacteroides fragilis-related carcinogenesis in colorectal cancer via the RHEB/mTOR pathway[J].Cell Death Dis,2019,10(9):675.[19]Liu F,Pan Z,Zhang J,et al.Overexpression of RHEB is associated with metastasis and poor prognosis in hepatocellular carcinoma[J].Oncol Lett,2018,15(3):3838-3845.[20]Xiang T,Cheng N,Huang B,et al.Important oncogenic and immunogenic roles of SPP1 and CSF1 in hepatocellular carcinoma[J].Med Oncol,2023,40(6):158.[21]Liu L,Zhang R,Deng J,et al.Construction of TME and Identification of crosstalk between malignant cells and macrophages by SPP1 in hepatocellular carcinoma[J].Cancer Immunol Immunother,2022,71(1):121-136.[22]Zhang Y,Li S,Cui X,et al.microRNA-944 inhibits breast cancer cell proliferation and promotes cell apoptosis by reducing SPP1 through inactivating the PI3K/Akt pathway[J].Apoptosis,2023,28(11/12):1546.[23]Wu Y,Zhang M,Bi X,et al.ESR1 mediated circ_0004018 suppresses angiogenesis in hepatocellular carcinoma via recruiting FUS and stabilizing TIMP2 expression[J].Exp Cell Res,2021,408(2):112804.[24]Dustin D,Gu G,Fuqua SAW.ESR1 mutations in breast cancer[J].Cancer,2019,125(21):3714-3728.[25]Dustin D,Gu G,Beyer AR,et al.RON signalling promotes therapeutic resistance in ESR1 mutant breast cancer[J].Br J Cancer,2021,124(1):191-206.

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更新日期/Last Update: 1900-01-01