Yuan Xiaoying, Huang Defa, Peng Liang, Lin Yilong, Wang Lijuan, Yan Jiawei, Qiu Youming, Song Chenggui, Wang Qi
The First School of Clinical Medicine, Gannan Medical University, Ganzhou, China.
Department of Laboratory Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Front Immunol. 2025 Jul 9;16:1558468. doi: 10.3389/fimmu.2025.1558468. eCollection 2025.
Hepatocellular carcinoma (HCC) is a highly malignant epithelial tumor characterized by global high incidence and poor clinical prognosis. Radical surgical resection, as the standard treatment for early-stage HCC patients, has been extensively validated for its therapeutic efficacy. However, epidemiological studies indicate that most patients are already in advanced stages at initial diagnosis, losing eligibility for radical treatment. Notably, HCC pathogenesis exhibits marked etiological heterogeneity, posing significant challenges for clinical management. Although significant breakthroughs have been made in understanding HCC drivers at pathophysiological levels, translational applications of these findings remain hindered by multiple barriers. Currently, elucidating the molecular mechanisms of HCC pathogenesis and identifying effective therapeutic targets constitute major research priorities in this field.Small extracellular vesicles (sEVs) are phospholipid bilayer vesicles (30-150 nm in diameter) carrying functional proteomes and nucleic acids (e.g., miRNAs, lncRNAs) with substantial biological activity. Studies demonstrate that sEVs contribute to malignant phenotype acquisition by modulating key signaling pathways such as PI3K/AKT and Wnt/β-catenin. These molecular cascades ultimately confer hallmark pathological features including aberrant proliferation, apoptosis resistance, and immune evasion to tumor cells. Within multi-network regulatory systems, sEVs serve as crucial intercellular messengers mediating tumor cell interactions with other tumor microenvironment (TME) components (e.g., cancer-associated fibroblasts, immune cells). Such communication facilitates TME reprogramming, pro-angiogenic phenotypic shifts, and therapy resistance development. Nevertheless, the precise molecular mechanisms of sEVs in HCC pathogenesis remain incompletely understood, warranting further exploration of their translational potential in clinical practice.
肝细胞癌（HCC）是一种高度恶性的上皮性肿瘤，其特点是全球发病率高且临床预后差。根治性手术切除作为早期HCC患者的标准治疗方法，其治疗效果已得到广泛验证。然而，流行病学研究表明，大多数患者在初诊时已处于晚期，失去了根治性治疗的资格。值得注意的是，HCC的发病机制表现出明显的病因异质性，给临床管理带来了重大挑战。尽管在病理生理水平上对HCC驱动因素的理解取得了重大突破，但这些发现的转化应用仍受到多种障碍的阻碍。目前，阐明HCC发病机制的分子机制并确定有效的治疗靶点是该领域的主要研究重点。
小细胞外囊泡（sEVs）是直径为30 - 150 nm的磷脂双分子层囊泡，携带具有大量生物活性的功能性蛋白质组和核酸（如miRNA、lncRNA）。研究表明，sEVs通过调节PI3K/AKT和Wnt/β - 连环蛋白等关键信号通路，促进恶性表型的获得。这些分子级联反应最终赋予肿瘤细胞包括异常增殖、抗凋亡和免疫逃逸等标志性病理特征。在多网络调节系统中，sEVs作为关键的细胞间信使，介导肿瘤细胞与其他肿瘤微环境（TME）成分（如癌症相关成纤维细胞、免疫细胞）的相互作用。这种通讯促进了TME重编程、促血管生成表型转变和治疗抗性的发展。然而，sEVs在HCC发病机制中的确切分子机制仍不完全清楚，需要进一步探索其在临床实践中的转化潜力。
