基于血管生成相关lncRNAs的肝细胞癌预后风险模型的构建及验证

doi:10.3969/j.issn.1009-976X.2024.01.002

摘要/Abstract

摘要： 目的构建并验证基于血管生成相关长非编码RNA评估肝细胞癌患者的预后风险模型。方法利用Pearson相关分析筛选出与血管生成相关lncRNA,提取差异表达的血管生成相关lncRNA。通过多因素Cox回归联合LASSO回归建立风险预后模型,并通过生存分析、独立预后分析、风险分析等进行验证。利用列线图模型进行预后预测、分析风险评分与免疫细胞、免疫微环境及免疫检查点表达的关系对预后模型进行评估。结果筛选出的血管生成相关的lncRNA构建的风险预后模型中,风险评分越高的HCC患者预后越差,巨噬细胞及Treg细胞的浸润也证明风险评分与免疫微环境改变相关。结论该模型对预测肝细胞癌患者的预后有较好的信度和效度。

关键词: 肝细胞癌, 血管生成, 长非编码RNA, 预后

Abstract: Objective To construct and validate a prognostic risk model based on long non-coding RNA associated with angiogenesis in hepatocellular carcinoma. Methods LncRNAs associated with angiogenesis were screened by Pearson correlation analysis and differentially expressed lncRNAs were extracted. Multivariate Cox regression combined with LASSO regression was used to establish the risk prognosis model, which was verified by survival analysis, independent prognosis analysis and risk analysis. The relationship between risk score and the expression of immune cells, immune microenvironment and immune checkpoint was analyzed. Results In the risk prognosis model constructed by screened angiogenation-related lncrnas, HCC patients with higher risk scores had worse prognosis, and the infiltration of macrophages and Treg cells also proved that risk scores were correlated with changes in the immune microenvironment. Conclusion The model has good reliability and validity in predicting the prognosis of patients with hepatocellular carcinoma.

Key words: hepatocellular carcinoma, angiogenesis, lncRNA, prognosis

中图分类号:

R735.7

罗婉蓉, 张文岳, 罗葆明. 基于血管生成相关lncRNAs的肝细胞癌预后风险模型的构建及验证[J]. 岭南现代临床外科, 2024, 24(01): 7-13.

LUO Wan-rong, ZHANG Wen-yue, LUO Bao-ming. Construction and validation of a prognostic risk model for hepatocellular carcinoma based on angiogenesis-related lncRNAs[J]. Lingnan Modern Clinics In Surgery, 2024, 24(01): 7-13.

参考文献

[1] Vogel A, Meyer T, Sapisochin G, et al.Hepatocellular carcinoma[J]. Lancet, 2022, 400(10360): 1345-1362.
[2] Tian T, Nan KJ, Wang SH, et al.PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cells[J]. Carcinogenesis, 2010, 31(7): 1211-1219.
[3] Kurebayashi Y, Matsuda K, Ueno A, et al.Immunovascular classification of HCC reflects reciprocal interaction between immune and angiogenic tumor microenvironments[J]. Hepatology, 2022, 75(5): 1139-1153.
[4] Morse MA, Sun W, Kim R, et al.The Role of Angiogenesis in Hepatocellular Carcinoma[J]. Clin Cancer Res, 2019, 25(3): 912-920.
[5] Tang W, Chen Z, Zhang W, et al.The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects[J]. Signal Transduct Target Ther, 2020, 5(1): 87.
[6] Statello L, Guo CJ, Chen LL, et al.Gene regulation by long non-coding RNAs and its biological functions[J]. Nat Rev Mol Cell Biol, 2021, 22(2): 96-118.
[7] Kopp F, Mendell JT.Functional Classification and Experimental Dissection of Long Noncoding RNAs[J]. Cell, 2018, 172(3): 393-407.
[8] Gao Y, Tong M, Wong TL, et al.Long Noncoding RNA URB1-Antisense RNA 1 (AS1) Suppresses Sorafenib-Induced Ferroptosis in Hepatocellular Carcinoma by Driving Ferritin Phase Separation[J]. ACS Nano, 2023, 17(22): 22240-22258.
[9] Ma J, Zhang L, Bian HR, et al.A Noninvasive Prediction Nomogram for Lymph Node Metastasis of Hepatocellular Carcinoma Based on Serum Long Noncoding RNAs[J]. Biomed Res Int, 2019, 2019:1710670.
[10] Chen Y, Wu X, Chen X, et al.LncRNA TGFB2-OT1 Promotes Progression and Angiogenesis in Hepatocellular Carcinoma by Dephosphorylating β-Catenin[J]. J Hepatocell Carcinoma, 2023, 10:429-446.
[11] Zhang L, Xu J, Zhou S, et al.Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma[J]. J Hepatol, 2024, 80(1): 82-98.
[12] Vogel A, Cervantes A, Chau I, et al.Correction to: “Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up"[J]. Ann Oncol, 2019, 30(5): 871-873.
[13] Llovet JM, Castet F, Heikenwalder M, et al.Immunotherapies for hepatocellular carcinoma[J]. Nat Rev Clin Oncol, 2022, 19(3): 151-172.
[14] Garcia J, Hurwitz HI, Sandler AB, Miles D, Coleman RL, Deurloo R, Chinot OL.Bevacizumab (Avastin®) in cancer treatment: A review of 15 years of clinical experience and future outlook[J]. Cancer Treat Rev, 2020, 86:102017.
[15] Lee HW, Xu Y, He L, et al.Role of Venous Endothelial Cells in Developmental and Pathologic Angiogenesis[J]. Circulation, 2021, 144(16): 1308-1322.
[16] Liu DL, Lu LL, Dong LL, et al.miR-17-5p and miR-20a-5p suppress postoperative metastasis of hepatocellular carcinoma via blocking HGF/ERBB3-NF-κB positive feedback loop[J]. Theranostics, 2020, 10(8): 3668-3683.
[17] Saigusa H, Mimura I, Kurata Y, et al.Hypoxia-inducible lncRNA MIR210HG promotes HIF1α expression by inhibiting miR-93-5p in renal tubular cells[J]. FEBS J, 2023, 290(16): 4040-4056.
[18] Dong Q, Qiu H, Piao C, et al.LncRNA SNHG4 promotes prostate cancer cell survival and resistance to enzalutamide through a let-7a/RREB1 positive feedback loop and a ceRNA network[J]. J Exp Clin Cancer Res, 2023, 42(1): 209.
[19] Zhu L, Zhu Y, Li F, et al.RNautophagic regulation of DNMT3a-dependent DNA methylation by Linc00942 enhances chemoresistance in gastric cancer[J]. Clin Transl Med, 2023, 13(7): e1337.
[20] Zhu L, Zhang XP, Xu S, et al.Identification of a CD4+ conventional T cells-related lncRNAs signature associated with hepatocellular carcinoma prognosis, therapy, and tumor microenvironment[J]. Front Immunol, 2023, 13: 1111246.
[21] Deng Y, Guo K, Tang Z, et al.Identification and experimental validation of a tumor-infiltrating lymphocytes-related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma[J]. Front Immunol, 2022, 13: 1046790.