罗慧妮,韦忠恒

肝细胞癌（Hepatocellular carcinoma，HCC）是全球癌症相关死亡的主要原因之一，其高发病率、高复发率和高死亡率对临床诊疗构成重大挑战。外泌体作为直径40至150nm的细胞外囊泡，携带包括长链非编码RNA（long non-coding RNA，lncRNA）在内的多种生物分子，在肿瘤发生发展中发挥关键作用。近年研究表明，外泌体来源的lncRNA如THEMIS2-211、CRNDE、ATB等具有作为HCC诊断标志物和预后预测因子的潜力。这些lncRNA通过参与基因组不稳定性调控、肿瘤微环境重塑等机制影响HCC进展，且在体液中稳定性高，易于检测。本文系统综述外泌体lncRNA在HCC早期诊断、预后评估和治疗反应预测中的研究进展，并探讨其临床应用前景与挑战。

外泌体；长链非编码RNA；肝细胞癌；诊断；预后；生物标志物

[1] YUE Y,TAO J,AN D,et al.A prognostic exosome-related long non-coding RNAs risk model related to the immune microenvironment and therapeutic responses for patients with liver hepatocellular carcinoma[J].Heliyon,2024,10(2):e24462. [2] SIEGEL RL,MILLER KD,JEMAL A.Cancer statistics,2020.CA Cancer[J].Clin,2020,70:7–30. [3] XU Y,YU X,ZHANG Q,et al.A novel classification of HCC basing on fatty-acid-associated lncRNA[J].Sci Rep,2022,12(1):18863. [4] GUPTA S,BENT S,K0HLWES J.Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C.A systematic review and critical analysis[J].Ann Intern Med,2003,139(1):46-50. [5] TAO Q,ZHU K,ZHAN Y,et al.Construction of a novel exosomes-related gene signature in hepatocellular carcinoma[J].Frontiers in cell and developmental biology,2022,10:997734. [6] CHEN W,MAO Y,LIU C,et al.Exosome in Hepatocellular Carcinoma:an update[J].Journal of Cancer,2021,12(9):2526-36. [7] DA COSTA VR,ARALDI RP,VIGERELLI H,et al.Exosomes in the Tumor Microenvironment:From Biology to Clinical Applications[J]. Cells,2021,10(10):2617. [8] SHI M,JIA J S,GAO G S,et al.Advances and challenges of exosome-derived noncoding RNAs for hepatocellular carcinoma diagnosis and treatment[J].Biochemistry and biophysics reports,2024,38:101695. [9] SHI Z,JIN S,LIU X,et al.The epigenetic regulatory network of long noncoding RNAs in hepatocellular carcinoma[J].Genes&diseases, 2025,12(5):101534. [10] WANG J,PU J,ZHANG Y,et al.Exosome-transmitted long non-coding RNA SENP3-EIF4A1 suppresses the progression of hepatocellular carcinoma[J].Aging(Albany NY),2020,12(12):11550-11567. [11] XIA H,HUANG Z,LIU S,et al.Exosomal Non-Coding RNAs:Regulatory and Therapeutic Target of Hepatocellular Carcinoma[J]. Frontiers in oncology,2021,11:653846. [12] ZHU K,YANG J,ZHU H,et al.Diagnostic value of exosome derived long noncoding RNA in gastric cancer in Chinese population:A PRISMA-compliant systematic review and meta-analysis[J].Medicine,2021,100(51):e28153. [13] SUN L,SU Y,LIU X,et al.Serum and exosome long non coding RNAs as potential biomarkers for hepatocellular carcinoma[J].Cancer, 2018,9(15):2631-2639. [14] CAO SQ,ZHENG H,SUN BC,et al.Long non-coding RNA highly up-regulated in liver cancer promotes exosome secretion.[J].World J Gastroenterol,2019,25(35):5283-5299. [15] TANG X,MIAO Y,WANG J,et al.Identification of Mutator-Derived lncRNA Signatures of Genomic Instability for Promoting the Clinical Outcome in Hepatocellular Carcinoma[J].Computational and mathematical methods in medicine,2021,2021:1205029. [16] LI X,LEI Y,WU M,et al.Regulation of Macrophage Activation and Polarization by HCC-Derived Exosomal lncRNA TUC339[J].Int J Mol Sci,2018,19(10):2958. [17] PAN Q,YI C,ZHANG Y.Overall Survival Signature of 5-Methylcytosine Regulators Related Long Non-Coding RNA in Hepatocellular Carcinoma[J].Frontiers in oncology,2022,12:884377. [18] WU J,LI X,YIN X,et al.Rapid detection of plasma exosomal LncRNA CASC9 for HCC using RT-RPA-CRISPR/Cas12a assay[J]. Journal of pharmaceutical and biomedical analysis,2025,266:117085. [19] WU J,LI X,YIN X,et al.Rapid detection of plasma exosomal LncRNA CASC9 for HCC using RT-RPA-CRISPR/Cas12a assay[J]. Journal of pharmaceutical and biomedical analysis,2025,266:117085. [20] ZHU L,LOU Y,XIAO Q,et al.Establishment and Evaluation of Exosomes-Related Gene Risk Model in Hepatocellular Carcinoma[J]. Biochemical genetics,2024,62(2):698-717. [21] YAO J,HUA X,SHI J,et al.LncRNA THEMIS2-211,a tumor-originated circulating exosomal biomarker,promotes the growth and metastasis of hepatocellular carcinoma by functioning as a competing endogenous RNA[J].FASEB journal,2022,36(4):e22238. [22] LU Y,DUAN Y,XU Q,et al.Circulating exosome-derived bona fide long non-coding RNAs predicting the occurrence and metastasis of hepatocellular carcinoma[J].Cell Mol Med,2020,24(2):1311-1318. [23] KIM S S,BAEK G O,SON J A,et al.Early detection of hepatocellular carcinoma via liquid biopsy:panel of small extracellular vesicle-derived long noncoding RNAs identified as markers[J].Molecular oncology,2021,15(10):2715-31. [24] WANG T,ZHU H,XIAO M,et al.Serum exosomal long noncoding RNA CRNDE as a prognostic biomarker for hepatocellular carcinoma[J].Journal of clinical laboratory analysis,2021,35(11):e23959. [25] LEE YR,KIM G,TAk WY,et al.Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma[J]. Int J Cancer,2019,144(6):1444-1452. [26] PENG W,BAI S,ZHENG M,et al.An exosome-related lncRNA signature correlates with prognosis,immune microenvironment,and therapeutic responses in hepatocellular carcinoma[J].Translational oncology,2023,31:101651. [27] HOU Y,YU Z,TAM N L,et al.Exosome-related lncRNAs as predictors of HCC patient survival:A prognostic model[J].Am J Transl Res. 2018;10:1648–1662. [28] NIE G,LIAN N,PENG D,et al.Prognostic value of exosomal noncoding RNA in hepatocellular carcinoma:a meta-analysis[J]. Carcinogenesis,2022,43(8):754-65. [29] WANG J,PU J,ZHANG Y,et al.Exosome-transmitted long non-coding RNA SENP3-EIF4A1 suppresses the progression of hepatocellular carcinoma[J].Aging(Albany NY).2020,12(12):11550-11567. [30] ZHAO B,ZHENG X,WANG Y,et al.Lnc-CCNH-8 promotes immune escape by up-regulating PD-L1 in hepatocellular carcinoma[J]. Mol Ther Nucleic Acids,2024,35(1):102125. [31] HUI B,LU C,WANG J,et al.Engineered exosomes for co-delivery of PGM5-AS1 and oxaliplatin to reverse drug resistance in colon cancer[J].Cell Physiol,2022,237(1):911-933. [32] HUANG X,WU W,JING D,et al.Engineered exosome as targeted lncRNA MEG3 delivery vehicles for osteosarcoma therapy[J]. Control Release,2022,343:107-117. [33] 叶开,李莉,徐雪莹,等.外泌体LncRNA SFTA1P和miR-483-3p诊断乙型肝炎病毒相关性肝癌的价值研究[J].齐齐哈尔医学院学报,2024,45(11):1007-11. [34] MIRZAEI-NASAB F,MAJD A,SEYEDENA Y,et al.Integrative analysis of exosomal ncRNAs and their regulatory networks in liver cancer progression[J].Practical laboratory medicine,2025,45:e00464.

点击下载PDF