切换至 "中华医学电子期刊资源库"

中华肝脏外科手术学电子杂志 ›› 2024, Vol. 13 ›› Issue (02) : 214 -219. doi: 10.3877/cma.j.issn.2095-3232.2024.02.016

基础研究

生物信息学分析CETP基因在肝癌中表达及其对预后和免疫的影响
陈显育1, 曾谣1, 莫钊鸿1, 翟航1, 张广权1, 钟造茂1, 陈署贤1,()   
  1. 1. 510630 广州,中山大学附属第三医院肝胆外科
  • 收稿日期:2024-01-04 出版日期:2024-04-10
  • 通信作者: 陈署贤

Bioinformatics analysis of CETP genes expression in primary liver cancer and its effects on prognosis and immunity

Xianyu Chen1, Yao Zeng1, Zhaohong Mo1, Hang Zhai1, Guangquan Zhang1, Zaomao Zhong1, Shuxian Chen1,()   

  1. 1. Department of Hepatobiliary Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2024-01-04 Published:2024-04-10
  • Corresponding author: Shuxian Chen
引用本文:

陈显育, 曾谣, 莫钊鸿, 翟航, 张广权, 钟造茂, 陈署贤. 生物信息学分析CETP基因在肝癌中表达及其对预后和免疫的影响[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 214-219.

Xianyu Chen, Yao Zeng, Zhaohong Mo, Hang Zhai, Guangquan Zhang, Zaomao Zhong, Shuxian Chen. Bioinformatics analysis of CETP genes expression in primary liver cancer and its effects on prognosis and immunity[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2024, 13(02): 214-219.

目的

探讨胆固醇酯转移蛋白(CETP)在原发性肝癌(肝癌)中表达及其对预后和免疫的影响。

方法

下载GEO数据集GSE101685、GSE45267、GSE62232,以及ImmPort数据库人类免疫相关基因(IRGs),联合筛选差异表达的下调基因并选择未研究过的基因CETP。使用UALCAN和Kaplan-Meier Plotter数据库分别分析CETP在肝癌中的表达和其与肝癌患者预后的关系。LinkedOmics数据库进行基因本体(GO)分析和KEGG通路基因富集分析。Timer数据库及TISIDB数据库分析CETP与肝癌免疫细胞浸润、免疫调节剂的相关性。

结果

3个肝癌数据集及ImmPort数据库筛选出共有的16个差异基因,从中选择下调的关键基因CETP。UALCAN数据库显示,与正常组织相比,CETP基因在肝癌组织中表达水平降低(P<0.05);CETP表达与美国癌症联合委员会(AJCC)分期、淋巴结转移密切相关(P<0.05)。Kaplan-Meier Plotter数据库分析显示,CETP基因低表达患者中位生存时间37.8个月,明显短于高表达患者的61.7个月(HR=0.66,P<0.05)。GO分析显示,CETP相关基因主要参与免疫反应、白细胞粘附、细胞死亡、细胞趋化等活动;KEGG通路分析显示,CETP基因在NK细胞介导的细胞毒性、细胞因子-细胞因子受体相互作用、氧化磷酸化、Th1和Th2细胞分化等通路中富集。TIMER数据库及TISIDB数据库表明CETP与肝癌中树突状细胞、CD8+T细胞免疫细胞浸润水平及免疫调节剂相关。

结论

在线数据库分析表明,CETP基因在肝癌中表达下调,CETP低表达与患者临床特征和不良预后相关,CETP表达的改变可影响免疫应答,从而可能影响患者预后。

Objective

To investigate the expression of cholesteryl ester transfer protein (CETP) in primary liver cancer (PLC) and evaluate its effect on prognosis and immunity.

Methods

The immune-related genes (IRGs) were downloaded from the Gene Expression Omnibus (GEO) datasets including GSE101685, GSE45267 and GSE62232 and ImmPort database. The down-regulated differentially-expressed genes (DEGs) were screened and the unstudied CETP was selected. The expression of CETP in PLC and its association with prognosis of PLC patients were analyzed using UALCAN and Kaplan-Meier Plotter databases, respectively. LinkedOmics database was employed for gene ontology (GO) analysis and KEGG pathway enrichment analysis. Timer and TISIDB databases were adopted to analyze the correlation between CETP and immune cell infiltration and immunomodulators of PLC.

Results

16 DEGs were screened from 3 liver cancer datasets and ImmPort database, and the down-regulated key gene of CETP was selected. According to the UALCAN database, the expression level of CETP genes in PLC tissues was lower than that in normal tissues (P<0.05). The expression level of CETP genes was intimately correlated with the American Joint Committee on Cancer (AJCC) staging and lymph node metastasis (P<0.05). Kaplan-Meier Plotter database analysis showed that the median survival of patients with low expression of CETP genes was 37.8 months, significantly shorter than 61.7 months of that with high expression of CETP genes (HR=0.66, P<0.05). GO analysis revealed that CETP-related genes were mainly involved in immune response, leukocyte adhesion, cell death and cell chemotaxis, etc. KEGG pathway analysis showed that CETP gene was enriched in NK cell-mediated cytotoxicity, cytokine-cytokine receptor interaction, oxidative phosphorylation, Th1 and Th2 cell differentiation and other signaling pathways. TIMER and TISIDB databases showed that CETP was associated with the infiltration levels of dendritic cells and CD8+T cells, and immunomodulators in PLC.

Conclusions

Online database analysis indicates that the expression level of CETP genes is down-regulated in PLC. Low expression of CETP genes is correlated with clinical characteristics and poor prognosis of patients. The changes of CETP genes expression can affect immune response, thereby probably affecting clinical prognosis of PLC patients.

图1 肝癌差异表达基因CETP的筛选注:a为数据集GSE101685差异表达基因表达火山图;b为数据集GSE45267差异表达基因表达火山图;c为数据集GSE62232差异表达基因表达火山图;d为3个数据集共有下调的14个差异表达基因与免疫相关基因Venn图;CETP为胆固醇酯转移蛋白
图2 CETP基因与肝癌患者临床及预后的关系注:a、b、c均来自于UALCAN数据库,a为正常组织和肝癌组织中CETP的表达,b为不同肿瘤分期患者的CETP表达,c为CETP在是否有淋巴结转移的肝癌患者中基因表达;d来自Kaplan-Meier Plotter数据库,CETP表达与肝癌患者总体生存关系的Kaplan-Meier生存曲线;CETP为胆固醇酯转移蛋白;***为P<0.001
图3 CETP基因共表达基因火山图注:左边绿色区域为与CETP负相关的基因,右边红色区域为与CETP正相关的基因;CETP为胆固醇酯转移蛋白
图4 CETP基因表达与肝癌免疫细胞及免疫调节剂的关系注:a为CETP与CD8+细胞及树突状细胞的关系,b为CETP与免疫调节剂CD274、CTLA4、PDCD1、LAG3的关系;CTLA4、PDCD1、LAG3分别为细胞毒性T淋巴细胞抗原、程序性细胞死亡蛋白1、淋巴细胞激活基因3,LIHC为肝细胞癌,CETP为胆固醇酯转移蛋白
[1]
Petta S, Craxi A. Hepatocellular carcinoma and non-alcoholic fatty liver disease: from a clinical to a molecular association[J]. Curr Pharm Des, 2010, 16(6):741-752.
[2]
Yang JD, Hainaut P, Gores GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(10):589-604.
[3]
Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021(7):6.
[4]
Harding-Theobald E, Louissaint J, Maraj B, et al. Systematic review: radiomics for the diagnosis and prognosis of hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2021, 54(7):890-901.
[5]
Piñero F, Dirchwolf M, Pessôa MG. Biomarkers in hepatocellular carcinoma: diagnosis, prognosis and treatment response assessment[J]. Cells, 2020, 9(6):1370.
[6]
Tosheska Trajkovska K, Topuzovska S. High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol[J]. Anatol J Cardiol, 2017, 18(2):149-154.
[7]
Barrett T, Wilhite SE, Ledoux P, et al. NCBI GEO: archive for functional genomics data sets-update[J]. Nucleic Acids Res, 2013(41):D991-995.
[8]
Bhattacharya S, Dunn P, Thomas CG, et al. ImmPort, toward repurposing of open access immunological assay data for translational and clinical research[J]. Sci Data, 2018(5):180015.
[9]
Chandrashekar DS, Karthikeyan SK, Korla PK, et al. UALCAN: an update to the integrated cancer data analysis platform[J]. Neoplasia, 2022(25):18-27.
[10]
Zheng Q, Min S, Zhou Q. Identification of potential diagnostic and prognostic biomarkers for LUAD based on TCGA and GEO databases[J]. Biosci Rep, 2021, 41(6):BSR20204370.
[11]
Wu Z, Wang Y, Li J, et al. MCM10 is a prognostic biomarker and correlated with immune checkpoints in ovarian cancer[J]. Front Genet, 2022(13):864578.
[12]
Lv Z, Feng HY, Tao W, et al. CD146 as a prognostic-related biomarker in ccRCC correlating with immune infiltrates[J]. Front Oncol, 2021(11):744107.
[13]
Ayuso C, Rimola J, Vilana R, et al. Diagnosis and staging of hepatocellular carcinoma (HCC):current guidelines[J]. Eur J Radiol, 2018(101):72-81.
[14]
Liu Z, Jiang Y, Yuan H, et al. The trends in incidence of primary liver cancer caused by specific etiologies: results from the Global Burden of Disease Study 2016 and implications for liver cancer prevention[J]. J Hepatol, 2019, 70(4):674-683.
[15]
Wang YC, Tian ZB, Tang XQ. Bioinformatics screening of biomarkers related to liver cancer[J]. BMC Bioinformatics, 2021, 22(Suppl 3):521.
[16]
Shen S, Kong J, Qiu Y, et al. Identification of core genes and outcomes in hepatocellular carcinoma by bioinformatics analysis[J]. J Cell Biochem, 2019, 120(6):10069-10081.
[17]
Alqahtani A, Khan Z, Alloghbi A, et al. Hepatocellular carcinoma: molecular mechanisms and targeted therapies[J]. Medicina, 2019, 55(9):526.
[18]
Pirillo A, Catapano AL. Pitavastatin and HDL: effects on plasma levels and function(s)[J]. Atheroscler Suppl, 2017(27):e1-9.
[19]
Deng S, Liu J, Niu C. HDL and cholesterol ester transfer protein (CETP)[J]. Adv Exp Med Biol, 2022(1377):13-26.
[20]
Schmidt AF, Hunt NB, Gordillo-Marañón M, et al. Cholesteryl ester transfer protein (CETP) as a drug target for cardiovascular disease[J]. Nat Commun, 2021, 12(1):5640.
[21]
Corsetti JP, Gansevoort RT, Navis G, et al. LPL polymorphism (D9N) predicts cardiovascular disease risk directly and through interaction with CETP polymorphism (TaqIB) in women with high HDL cholesterol and CRP[J]. Atherosclerosis, 2011, 214(2):373-376.
[1] 刘政宏, 王凤力, 吉亚君, 高佳. 胃癌中ELK3蛋白的表达与临床病理特征和预后的关系研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 155-159.
[2] 张琳, 李婷. CRIP1在胃癌中的表达及与临床病理指标和预后的关系研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 171-175.
[3] 鲁鑫, 杨琴, 许佳怡. 不同术式治疗恶性梗阻性黄疸疗效及对免疫功能的影响[J]. 中华普外科手术学杂志(电子版), 2024, 18(02): 180-183.
[4] 栗艳松, 冯会敏, 刘明超, 刘泽鹏, 姜秋霞. STIP1在三阴性乳腺癌组织中的表达及临床意义研究[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 52-56.
[5] 曹飞, 庞俊. 前列腺癌免疫微环境中免疫抑制性细胞分类及其作用机制[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(02): 121-125.
[6] 黄艺承, 梁海祺, 何其焕, 韦发烨, 杨舒博, 谭舒婷, 翟高强, 程继文. 机器学习模型评估RAS亚家族基因对膀胱癌免疫治疗的作用[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(02): 131-140.
[7] 朱显钟, 李金雨, 于忠英, 温路生. 淋巴结平均直径与无淋巴结转移肾癌病理特征及预后关系研究[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(02): 146-151.
[8] 谭智勇, 付什, 李宁, 王海峰, 王剑松. 膀胱小细胞癌发病机制及其诊疗研究进展[J]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(02): 183-187.
[9] 白睿, 孙备. 自身免疫性胰腺炎和胰腺导管腺癌鉴别的策略与思考[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 121-126.
[10] 王礼光, 严庆, 廖珊, 符荣党, 陈焕伟. 微血管侵犯及手术切缘对肝细胞癌患者术后生存预后的影响[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 151-157.
[11] 杨建彬, 陈建华, 张文华, 刘建东. 中心静脉压差值对腹腔镜肝细胞癌肝切除术中出血的影响[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 158-162.
[12] 马振威, 朱博, 刘赋斌, 邓正栋, 王剑明. 血小板和淋巴细胞比值联合CA19-9在胆囊癌术后患者预后评估中的价值[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 163-168.
[13] 夏辉, 戴斌, 冉君, 王威, 龚昭, 周程. DEP结构域蛋白1B在肝细胞癌中的表达及功能[J]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 205-213.
[14] 卓长华, 叶韵斌, 陈昌江, 简锦亮, 王志纬. 林奇综合征相关性异时性结直肠癌的治疗[J]. 中华结直肠疾病电子杂志, 2024, 13(01): 32-37.
[15] 赵海清, 张威, 李琴. 肌苷联合免疫检查点抑制剂在转移性结直肠癌患者中的临床疗效观察[J]. 中华结直肠疾病电子杂志, 2024, 13(01): 54-62.
阅读次数
全文


摘要