胰腺导管腺癌术后早期肝转移的危险因素及机制

祁春晖; 黄楚钧; 吕鹏飞; 杨庭楷; 李斌; 朱晓亮

doi:10.12449/JCH260735

胰腺导管腺癌术后早期肝转移的危险因素及机制

DOI: 10.12449/JCH260735

祁春晖^{1, 2},
黄楚钧^{1, 2},
吕鹏飞^{1, 2, 3, 4, 5},
杨庭楷^{1, 2, 3, 4, 5},
李斌^{1, 2, 3, 4, 5},
朱晓亮^{1, 2, 3, 4, 5, , ,}

1.
兰州大学第一临床医学院，兰州 730000
2.
兰州大学第一医院普外科，兰州 730000
3.
兰州大学第一医院普通外科国家临床重点专科，兰州 730000
4.
兰州大学第一医院精准医学实验室，兰州 730000
5.
甘肃省生物治疗与再生医学重点实验室，兰州 730000

基金项目:

科学技术部国家重点研发计划 (2022YFC2503602);

甘肃省科学技术厅联合科研基金重大项目 (24JRRA909);

甘肃省自然科学基金 (25JRRA1003)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：祁春晖负责设计论文框架，起草论文；黄楚钧、吕鹏飞负责查找资料、绘制图表；李斌、杨庭楷负责拟定写作思路；朱晓亮负责指导撰写文章并定稿。

详细信息

通信作者:
朱晓亮， zhuxiaoliang1981@163.com （ORCID： 0000-0002-5697-9583）

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出版历程
- 收稿日期: 2025-11-27
- 录用日期: 2026-01-12
- 出版日期: 2026-07-25

Risk factors for early postoperative liver metastasis in pancreatic ductal adenocarcinoma and related mechanisms

Chunhui Qi^{1, 2},
Chujun Huang^{1, 2},
Pengfei Lyu^{1, 2, 3, 4, 5},
Tingkai Yang^{1, 2, 3, 4, 5},
Bin Li^{1, 2, 3, 4, 5},
Xiaoliang Zhu^{1, 2, 3, 4, 5
, ,
,}

1.
The First Clinical Medical College of Lanzhou University，Lanzhou 730000，China
2.
Department of General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China
3.
National Clinical Key Specialty of General Surgery，The First Hospital of Lanzhou University，Lanzhou 730000，China
4.
Precision Medicine Laboratory，The First Hospital of Lanzhou University，Lanzhou 730000，China
5.
Gansu Provincial Key Laboratory of Biotherapy and Regenerative Medicine，Lanzhou 730000，China

Research funding:

National Key R&D Program of China (2022YFC2503602);

Major Joint Project of Gansu Provincial Science and Technology Department (24JRRA909);

Natural Science Foundation of Gansu Province (25JRRA1003)

More Information

Corresponding author: Zhu Xiaoliang， zhuxiaoliang1981@163.com （ORCID： 0000-0002-5697-9583）

摘要

摘要: 胰腺导管腺癌恶性程度高、预后极差，术后早期肝转移是影响预后的关键因素之一。本文结合近年临床与基础研究，概述胰腺导管腺癌术后早期肝转移的临床危险因素，并从肿瘤来源外泌体驱动的肝脏转移前微环境构建、转移相关巨噬细胞与中性粒细胞胞外诱捕网维持的促转移微环境、肿瘤细胞侵袭与肝向性迁移，以及肝内免疫代谢适应和纤维化重塑等方面，系统梳理术后早期肝转移的关键分子事件，以期为围手术期风险分层与干预策略的制订提供理论依据。
- 癌，胰腺管 /
- 肿瘤转移 /
- 危险因素
Abstract: Pancreatic ductal adenocarcinoma （PDAC） is highly malignant and often has an extremely poor prognosis， and early postoperative liver metastasis is one of the key influencing factors for prognosis. With reference to the clinical and experimental studies in recent years， this article reviews the clinical risk factors for early liver metastasis after PDAC and systematically elaborates on major molecular events underlying early postoperative liver metastasis from various aspects of construction of the pre-metastatic niche in the liver driven by tumor-derived exosomes， the pro-metastatic microenvironment maintained by metastasis-associated macrophages and neutrophil extracellular traps， the invasive phenotype and liver-tropic migration of tumor cells， intrahepatic immunometabolic adaptation， and fibrotic remodeling， in order to provide a theoretical basis for perioperative risk stratification and the development of intervention strategies.
- Carcinoma， Pancreatic Ductal /
- Neoplasm Metastasis /
- Risk Factors

HTML全文

注： TEX，肿瘤细胞来源外泌体；TNF-α，肿瘤坏死因子α；TGF-β，转化生长因子β；VEGF-A，血管内皮生长因子A；MIF，巨噬细胞迁移抑制因子；GJA1，缝隙连接蛋白A1；ZO-1，紧密连接蛋白1；MDSC，髓源性抑制性细胞；HSC，肝星状细胞；ECM，细胞外基质；PMN，转移前微环境；NKG2D，自然杀伤细胞2族成员D；Smad，母系抗十五表态蛋白同源物；CD44v6，CD44变异体6；ANXA1，膜联蛋白A1；c-Met，肝细胞生长因子受体；miR-30b-5p，微RNA-30b-5p；miR-27a，微RNA-27a；circ-IARS，环状RNA-IARS；tRF-GluCTC-0005，谷氨酸tRNA来源片段GluCTC-0005；NK细胞，自然杀伤细胞；C1QBP，补体C1q结合蛋白；Netrin-1，轴突导向因子1。

图 1 TEX介导PMN形成的相关机制

Figure 1. Mechanisms of tumor cell-derived exosome-mediated formation of the pre-metastatic niche

下载: 全尺寸图片幻灯片

注： TEX，肿瘤细胞来源外泌体；PMN，转移前微环境；MAM，转移相关巨噬细胞；NET，中性粒细胞胞外诱捕网；CAF，癌相关成纤维细胞；CXCL12，CXC亚族趋化因子配体12；CXCR4，CXC亚族趋化因子受体4；circRTN4，环状RNA网状蛋白4；PCSK9，前蛋白转化酶枯草芽孢杆菌蛋白酶9；TFAP2A，转录因子AP-2α；BMP4，骨形态发生蛋白4；TGF-β，转化生长因子β；RRM2，核糖核苷二磷酸还原酶M2；YBX1，Y盒结合蛋白1；HDAC4，组蛋白去乙酰化酶4；PAK2，p21活化激酶2；NPTX1，神经元特异性五聚蛋白1；RGRN，前颗粒蛋白；CFTR，囊性纤维化跨膜传导调节蛋白；TGFBR1，转化生长因子β受体1；S100蛋白家族，S100钙结合蛋白家族；MybL1，Myb样转录因子1；YAP，Yes相关蛋白；RHAMM^B，透明质酸介导运动受体B异构体；TRAF3IP2-AS1，TRAF3IP2反义RNA 1。

图 2 胰腺导管腺癌肝转移相关机制

Figure 2. Mechanisms underlying liver metastasis in ductal adenocarcinoma of pancreas

下载: 全尺寸图片幻灯片

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