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目的探讨突触结合蛋白1(SYT1)在肝细胞癌(HCC)中的表达及其临床价值。方法生物信息学检索SYT1亚细胞定位和在肿瘤微环境(TME)中的表达及预测其对HCC进展的生物学功能。UALCAN、TIMER3.0、HPA数据库与IHC验证SYT1在HCC组织中的表达并分析其与MKI67相关性。联合GEPIA2、TIMER3.0数据库及R语言分析，探究SYT1表达水平与HCC患者预后关联并开展生存分析。利用慢病毒进行SYT1基因沉默并采用集落形成、EdU、细胞划痕及Transwell实验探究SYT1对HCC细胞生物学行为的影响。裸鼠成瘤实验验证SYT1的促癌作用。结果生物信息学预测显示SYT1定位于细胞膜与胞质且其家族基因表达以正相关为主。在HCC组织中SYT1表达显著上调(P=2.93×10-10)且与MKI67呈正相关(ρs=0.419，P=3.3×10-17)。生存分析表明，在HCC中SYT1高表达预示着较差的总生存期(P=0.015)与疾病特异性生存期(P=0.0462)。免疫特征分析显示，SYT1在TME的单核/巨噬细胞、B细胞及恶性细胞等中呈高表达。富集分析显示SYT1可能参与多条HCC进展相关通路(P<0.05)。IHC表明SYT1在HCC组织中染色程度上调(P<0.0001)。细胞实验表明，沉默SYT1抑制HCC细胞增殖、迁移、侵袭(P<0.01)；动物实验表明，敲低SYT1可抑制肿瘤生长(P<0.001)。结论SYT1在HCC中表达上调且与不良预后密切相关，可促进HCC细胞增殖、迁移、侵袭及体内肿瘤生长，有望成为HCC临床治疗潜在新靶点。
Abstract：Objective To investigate the expression of synaptotagmin 1 (SYT1) in hepatocellular carcinoma (HCC) and its clinical value. Methods Bioinformatics analysis was performed to predict the subcellular localization and expression of SYT1 in the tumor microenvironment (TME)， as well as its biological functions in the progression of HCC. The expression of SYT1 in HCC tissues was verified by UALCAN， TIMER3.0 and HPA databases combined with IHC， and its correlation with MKI67 was analyzed. Combined with GEPIA2， TIMER3.0 databases and R language， the association of SYT1 expression level with the prognosis of HCC patients was explored， and survival analysis was carried out. Lentivirus-mediated SYT1 gene silencing was conducted， and the effects of SYT1 on the biological behaviors of HCC cells were explored by colony formation assay， EdU staining assay， cell scratch assay， and Transwell assay. The tumor-promoting effect of SYT1 was further validated in a nude mouse xenograft model. Results Bioinformatics prediction indicated that SYT1 is localized to the cell membrane and cytoplasm， and the expression of its family genes is mainly positively correlated. In HCC tissues， SYT1 expression was significantly upregulated (P=2.93×10-10) and positively correlated with MKI67 (ρs=0.419， P=3.3×10-17). Survival analysis showed that high SYT1 expression predicted poorer overall survival (P=0.015) and disease-specific survival (P=0.046 2) in HCC. Immune profiling analysis demonstrated that SYT1 was highly expressed in monocytes/macrophages， B cells and malignant cells in the TME. Enrichment analysis indicated that SYT1 may participate in multiple signaling pathways associated with HCC progression (P<0.05). IHC confirmed that the staining intensity of SYT1 was elevated in HCC tissues (P<0.000 1). Cellular assays showed that silencing SYT1 suppressed the proliferation， migration， and invasion of HCC cells (P<0.01). Animal experiments demonstrated that knockdown of SYT1 inhibited tumor growth in vivo (P<0.001). Conclusion SYT1 is upregulated in HCC and closely correlated with poor prognosis. It can promote the proliferation， migration and invasion of HCC cells as well as in vivo tumor growth， and is expected to become a potential novel target for the clinical treatment of HCC.
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基本信息:
中图分类号:R735.7
引用信息:
[1]陈骑东,韩红彪,凌潜龙,等.SYT1在肝癌中的表达及临床价值：基于生物信息学与实验[J].安徽医科大学学报().
基金信息:
安徽省高校自然科学研究项目（编号：2025AHGXZK20235、2023AH040392、2022AH052337）; 蚌埠医科大学研究生科研创新项目（编号：Byycx25033）
2026-07-22
2026-07-22
2026-07-22