循环游离核酸在肝细胞肝癌临床诊治中的应用进展

doi:10.3969/j.issn.1673-8640.2019.07.021

摘要/Abstract

摘要：

肝细胞肝癌（HCC）是在慢性肝病或肝硬化的基础上逐渐演变形成,是一个多因素、多步骤的发展、恶化过程。由于早期诊断率低,大多数HCC患者在初诊时已处于中晚期或发生肝外转移,常预后不良。随着基因组学研究及其在临床应用中的进展,循环游离核酸（cfNA）等一系列新型标志物相继被发现。cfNA在HCC患者的早期诊断、疗效监测、预后评价及个体化治疗等方面均显示出较好的临床应用前景。文章着重介绍了循环肿瘤DNA（ctDNA）、微小RNA（miRNA）、长链非编码RNA（lncRNA）及环状RNA（circRNA）这4种cfNA在HCC诊治中的应用进展。

关键词: 循环游离核酸, 肝细胞癌, 循环肿瘤DNA, 微小RNA, 长链非编码 RNA, 环状RNA

Abstract:

Hepatocellular carcinoma（HCC） is gradually formed on the basis of chronic liver disease or cirrhosis by a multi-factor and multi-step process of tumor progression. Due to the low determination rate in early diagnosis,the majority of patients with HCC are determined at the middle and advanced stages or accompanied by extrahepatic metastasis with poor prognosis. Recent advances in genomics and its clinical application have discovered a series of novel markers,such as circulating free nucleic acid（cfNA）,supported by research data,to be considered having a good clinical application prospect for clinical early diagnosis,the monitoring of therapeutic efficacy,prognosis evaluation and individualized treatment of patients with HCC. This review focuses on the clinical application of circulating tumor DNA（ctDNA）,microRNA（miRNA）,long non-coding RNA（lncRNA） and circular RNA（circRNA） in the diagnosis and treatment of HCC.

Key words: Circulating free nucleic acid, Hepatocellular carcinoma, Circulating tumor DNA, MicroRNA, Long non-coding RNA, Circular RNA

中图分类号:

R446.1

明心亮, 刘雪芳, 朱满综述, 涂建成审校. 循环游离核酸在肝细胞肝癌临床诊治中的应用进展[J]. 检验医学, 2019, 34(7): 667-671.

MING Xinliang, LIU Xuefang, ZHU Man, TU Jiancheng. Clinical application progress of circulating free nucleic acid in the diagnosis and treatment of hepatocellular carcinoma[J]. Laboratory Medicine, 2019, 34(7): 667-671.

图/表 1

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cfNA	类别	变化	作用	应用	评价	参考文献
ctDNA	浓度	增高	与肿瘤增大和预后不良相关	诊断、预后	无创无损、实时多次易获取、灵敏、准确、假阳性率低,但半衰期短、易降解、个体差异大、易受治疗影响、易出现新遗传变异	[1] [7] [9,36]
	甲基化	突变	与细胞过度凋亡、肿瘤发生相关	诊断、预后		[11]
	完整性	增加	与肿瘤状态相关	诊断、治疗		[10]
miRNA	miR-429	下调	促进HCC细胞的增殖和迁移	预测、预防	检测无创、稳定,早期阶段表现异常,研究方法简便,但序列较短有较高的脱靶效应,检测成本较高	[18,37]
	miR-122	下调	与预后不良和转移性增加有关	预后		[17]
	miR-367-3p	下调	促进HCC细胞转移和侵袭	治疗		[23]
	miR-224	上调	加速细胞生长、增强HCC侵袭性	诊断、监测		[20]
	miR-21	上调	增加细胞增殖并抑制凋亡	筛查、诊断、预后		[21]
lncRNA	SPRY4-IT1	上调	与分化、肿瘤大小和TNM 分期相关	诊断、预后	序列长,遗传信息丰富、多样化和特异性强,但表达量低,测定困难, 肝癌诊断分型预后方面的研究比较少,缺乏大样本、前瞻性的随机对照研究	[28]
	MALAT	上调	加速肝细胞增殖和周期进程	诊断、预测		[24]
	PVT1	上调	促进细胞增殖、调节细胞周期	筛查、诊断、预后		[27]
	HULC	上调	与肿瘤发生、生长和侵袭相关	预测、诊断、预后		[26]
	Linc00152	上调	预测肿瘤发生、肿瘤生长和肿瘤转移	预测、预后		[26]
	RP11-466I1.1	上调	促进肿瘤侵袭	预后		[29]
circRNA	hsa_circ_0001445	下调	抑制细胞凋亡和促进增殖、侵袭	诊断	稳定,不易降解,但与肿瘤特异性表达特征的形成机制尚不清楚	[32]

cfNA	类别	变化	作用	应用	评价	参考文献
ctDNA	浓度	增高	与肿瘤增大和预后不良相关	诊断、预后	无创无损、实时多次易获取、灵敏、准确、假阳性率低,但半衰期短、易降解、个体差异大、易受治疗影响、易出现新遗传变异	[1] [7] [9,36]
	甲基化	突变	与细胞过度凋亡、肿瘤发生相关	诊断、预后		[11]
	完整性	增加	与肿瘤状态相关	诊断、治疗		[10]
miRNA	miR-429	下调	促进HCC细胞的增殖和迁移	预测、预防	检测无创、稳定,早期阶段表现异常,研究方法简便,但序列较短有较高的脱靶效应,检测成本较高	[18,37]
	miR-122	下调	与预后不良和转移性增加有关	预后		[17]
	miR-367-3p	下调	促进HCC细胞转移和侵袭	治疗		[23]
	miR-224	上调	加速细胞生长、增强HCC侵袭性	诊断、监测		[20]
	miR-21	上调	增加细胞增殖并抑制凋亡	筛查、诊断、预后		[21]
lncRNA	SPRY4-IT1	上调	与分化、肿瘤大小和TNM 分期相关	诊断、预后	序列长,遗传信息丰富、多样化和特异性强,但表达量低,测定困难, 肝癌诊断分型预后方面的研究比较少,缺乏大样本、前瞻性的随机对照研究	[28]
	MALAT	上调	加速肝细胞增殖和周期进程	诊断、预测		[24]
	PVT1	上调	促进细胞增殖、调节细胞周期	筛查、诊断、预后		[27]
	HULC	上调	与肿瘤发生、生长和侵袭相关	预测、诊断、预后		[26]
	Linc00152	上调	预测肿瘤发生、肿瘤生长和肿瘤转移	预测、预后		[26]
	RP11-466I1.1	上调	促进肿瘤侵袭	预后		[29]
circRNA	hsa_circ_0001445	下调	抑制细胞凋亡和促进增殖、侵袭	诊断	稳定,不易降解,但与肿瘤特异性表达特征的形成机制尚不清楚	[32]