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液体活检在胰腺癌早期筛查诊断中的应用
DOI: 10.12449/JCH260636
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：陈俊宇负责设计论文框架，起草论文；赵攀、李霄负责论文修改；岳树强、刘正才负责拟定写作思路，指导撰写文章并最后定稿。
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摘要: 胰腺癌临床表现隐匿、恶性程度高，常规影像学检查与糖类抗原19-9检测对胰腺癌早期病变敏感度和特异度不足，早期诊断困难严重制约了胰腺癌患者的长期生存。液体活检以体液样本中循环肿瘤细胞、循环肿瘤DNA、循环肿瘤微小RNA、细胞外囊泡等标志物为检测靶标，具有无创、可连续监测等优势。本文系统综述液体活检在胰腺癌早期筛查诊断、复发预测和预后评估等方面的最新进展，以期为高危人群精准筛查与临床转化提供新思路和参考。Abstract: Pancreatic cancer is characterized by occult clinical manifestations and high malignancy， and conventional imaging examinations and carbohydrate antigen 19-9 lack sufficient sensitivity and specificity for detecting early-stage pancreatic cancer lesions. Difficulty in early diagnosis severely restricts the long-term survival of pancreatic cancer patients. Liquid biopsy targets the biomarkers in body fluid samples， including circulating tumor cells， circulating tumor DNA， circulating tumor microRNA， and extracellular vesicles， showing the advantages of noninvasiveness and continuous monitoring. This review systematically summarizes the latest advances in liquid biopsy for the early screening and diagnosis， recurrence prediction， and prognostic assessment of pancreatic cancer， aiming to provide new insights and references for precision screening of high-risk populations and the clinical translation of liquid biopsy.
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注： 在胰腺癌发生发展过程中，肿瘤细胞释放DNA、miRNA、外泌体等生物活性物质，肿瘤细胞（簇）亦可通过主动侵袭或被动脱落进入循环。液体活检通过采集血液等体液标本经过分离提取、富集纯化等步骤获取CTC、ctDNA、ct-miRNA、EV等标志物进行检测分析以实现早期筛查、诊断等目的。CTC，循环肿瘤细胞；ctDNA，循环肿瘤DNA；ct-miRNA，循环肿瘤微小RNA；EV，细胞外囊泡。
图 1 液体活检技术在胰腺癌早筛诊断中的应用
Figure 1. Application of liquid biopsy in early screening and diagnosis of pancreatic cancer
表 1 不同液体活检技术对胰腺癌早期筛查诊断的临床应用效能
Table 1. Clinical performance of different assay techniques for early screening and diagnosis of pancreatic cancer
检验技术 方法 研究对象 诊断策略 敏感度
（%）特异度
（%）AUC 参考文献 CTC 惯性微流控CTC富
集结合机器学习分
析技术良性胰腺疾病13例、胰腺癌26例
（Ⅰ/Ⅱ期13例、Ⅲ/Ⅳ期13例）联合门静脉CTC、外周血
CTC和CA19-980.80 92.30 0.944 ［22］ ctDNA cfDNA甲基化定量检
测分析对照组95例、慢性胰腺炎8例、胰
腺癌39例（Ⅰ期8例、ⅡA期9例、
ⅡB期20例、Ⅲ/Ⅳ期2例）cfDNA双基因（ADAMTS1、
BNC1）甲基化水平97.4 91.6 0.95 ［23］ 基于NGS技术对
ctDNA中抑癌基因甲
基化水平的检测
分析健康对照20例、胰腺良性疾病39
例、胰腺癌43例（Ⅰ期11例、Ⅱ期
18例、Ⅲ期10例、Ⅳ期4例）联合ctDNA四基因
（RASSF1A、EYA2、p16、
ppENK）甲基化水平和
CA19-9100 77.81 0.96 ［24］ ct-miRNA 基于机器学习对ct-
miRNA和外泌体
miRNA的测序分析
和定量检测非疾病对照124例（测序组57例，
分析组67例）、Ⅰ/Ⅱ期胰腺癌135
例（测序组44例、分析组91例）联合13-miRNA（5种循环
游离miRNA和8种循环
外泌体RNA）与CA19-993 — 0.99 ［25］ EV 基于外泌体lncRNA
全转录组测序和定
量检测对照组70例、胰腺癌78例（Ⅰ/Ⅱ
期59例、Ⅲ/Ⅳ期19例）4种外泌体lncRNA
（LINC01268、INC02802、
AC124854.1、L132657.1）
组合72 89 0.847 6 ［26］ MACS外泌体表面标
志物检测分析技术对照组51例、胰腺炎21例、胰腺
癌48例联合外泌体表面标志物
CD40、CD25和CA19-984.3 87.7 0.92 ［27］ 注：CTC，循环肿瘤细胞；ctDNA，循环肿瘤DNA；ct-miRNA，循环肿瘤微小RNA；EV，细胞外囊泡；cfDNA，细胞游离DNA；NGS，下一代DNA测序；MACS，磁性细胞分选技术；lncRNA，长链非编码RNA；CA19-9，糖类抗原19-9；AUC，曲线下面积。
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