Different Body Fluid Biopsies for Detecting Minimal Residual Disease in Lung Cancer: a Review of the Latest Advances

doi:10.12114/j.issn.1007-9572.2022.0641

Chinese General Practice ›› 2023, Vol. 26 ›› Issue (03): 280-286.DOI: 10.12114/j.issn.1007-9572.2022.0641

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Different Body Fluid Biopsies for Detecting Minimal Residual Disease in Lung Cancer: a Review of the Latest Advances

1.Department of Thoracic Surgery, the Second Hospital of Dalian Medical University, Dalian 116000, China
2.Inner Mongolia Medical University, Hohhot 015000, China

Received:2022-07-11 Revised:2022-10-11 Published:2023-01-20 Online:2022-10-17
Contact: LIU Changhong
About author:
YAN X, LIU S M, LIU C H. Different body fluid biopsies for detecting minimal residual disease in lung cancer: a review of the latest advances [J] . Chinese General Practice, 2023, 26 (3) : 280-286. YAN Xing and LIU Shanmei are co-first authors

不同体液标本活检在肺癌微小残留疾病监测中的应用最新进展

1．116000　辽宁省大连市，大连医科大学第二附属医院胸外科
2．015000　内蒙古自治区呼和浩特市，内蒙古医科大学

通讯作者: 刘长宏
作者简介:
闫星，刘山梅，刘长宏.不同体液标本活检在肺癌微小残留疾病监测中的应用最新进展[J].中国全科医学，2023，26（3）：280-286.[www.chinagp.net] 作者贡献：闫星提出研究选题方向，负责相关内容的文献收集和整理，并撰写论文初稿；刘山梅参与文献的收集和整理，负责论文的修订，与闫星在文章中所做同等贡献；刘长宏负责文章的质量控制及审校，对文章整体负责；所有作者确认了论文的最终稿。闫星与刘山梅为共同第一作者
基金资助:
辽宁省自然科学基金资助项目(20180550364)

Abstract

Abstract:

Post-treatment recurrence is a major difficulty in the treatment of lung cancer, one of the deadliest cancers worldwide. Minimal residual disease (MRD) as a "bridgehead" for the recurrence of solid tumors, is described as the presence of free circulating tumor cells or other tumor cell derivatives in the biological fluid of patients without any clinical cancer symptoms after the primary tumor treatment. China recently issued its first Consensus on the Detection and Clinical Application of MRD in Lung Cancer, aiming at improving the postoperative individualized treatment for lung cancer patients in accordance with the MRD status detected by the liquid biopsy. We reviewed the latest advances in the use of several most widely used body fluids (peripheral blood, urine, saliva, sputum and pleural effusion) in the detection of MRD in lung cancer, and discussed their values in guiding the precise treatment of MRD in lung cancer.

Key words: Lung neoplasms, Liquid biopsy, Neoplasm, residual, Circulating tumor DNA, Review

摘要：

肺癌是世界上致死率最高的恶性肿瘤之一，治疗后复发是其难以攻克的主要原因。微小残留疾病（MRD）作为实体瘤复发的"桥头堡"，被描述为治疗原发肿瘤后，在没有任何癌症临床症状的情况下，患者的生物液体中仍然存在游离的循环肿瘤细胞或其他肿瘤细胞衍生物。2021年中国达成了首个"肺癌MRD的检测和临床应用共识"，旨在通过液体活检监测以评估肺癌患者MRD状态，进而完善其术后个体化治疗。本文综述了几种热点液体（外周血、尿液、唾液、痰液、胸腔积液）标本在肺癌MRD检测中的进展，并探讨其指导肺癌MRD精准治疗的应用价值。

关键词: 肺肿瘤, 液体活组织检查, 肿瘤，残留, 循环肿瘤DNA, 综述

YAN Xing,LIU Shanmei,LIU Changhong. Different Body Fluid Biopsies for Detecting Minimal Residual Disease in Lung Cancer: a Review of the Latest Advances[J]. Chinese General Practice, 2023, 26(03): 280-286. DOI: 10.12114/j.issn.1007-9572.2022.0641.
闫星,刘山梅,刘长宏. 不同体液标本活检在肺癌微小残留疾病监测中的应用最新进展[J]. 中国全科医学, 2023, 26(03): 280-286. DOI: 10.12114/j.issn.1007-9572.2022.0641.

Figures/Tables 2

References 48

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体液类型	主要活检成分	优势	挑战
血液	CTC，ctDNA，外泌体	成熟的分析方法，可实时监测肿瘤进展，适用于最多的患者，应用更为普遍、广泛	高假阴性率，生物标志物质量和数量低，生物标志物半衰期较短，不能连续采集
尿液	CTC，ctDNA，尿液mRNA，外泌体	样本量大，无创、可以连续采集，适合纵向随访，对肿瘤转移有较高的反应	收集过程易受污染，肾脏滤过后数量下降
唾液	唾液mRNA，miRNA	无创操作，交叉污染风险低，可实时监测肺癌进展	样本量较少，生物标志物质量和数量低，复杂的成分，包括酶、抗体、激素等
痰液	痰液mRNA，miRNA，lncRNA，外泌体	无创操作，早期中央型肺癌灵敏度、特异度较高，肿瘤内异质性	样本量较少，缺乏成熟采样手段
胸腔积液（包括上清液）	CTC，ctDNA，积液mRNA	生物标志物质量和数量高，与临床特征高度相关	有创操作，不能实时监测肺癌进展，早期患者不适用

体液类型	主要活检成分	优势	挑战
血液	CTC，ctDNA，外泌体	成熟的分析方法，可实时监测肿瘤进展，适用于最多的患者，应用更为普遍、广泛	高假阴性率，生物标志物质量和数量低，生物标志物半衰期较短，不能连续采集
尿液	CTC，ctDNA，尿液mRNA，外泌体	样本量大，无创、可以连续采集，适合纵向随访，对肿瘤转移有较高的反应	收集过程易受污染，肾脏滤过后数量下降
唾液	唾液mRNA，miRNA	无创操作，交叉污染风险低，可实时监测肺癌进展	样本量较少，生物标志物质量和数量低，复杂的成分，包括酶、抗体、激素等
痰液	痰液mRNA，miRNA，lncRNA，外泌体	无创操作，早期中央型肺癌灵敏度、特异度较高，肿瘤内异质性	样本量较少，缺乏成熟采样手段
胸腔积液（包括上清液）	CTC，ctDNA，积液mRNA	生物标志物质量和数量高，与临床特征高度相关	有创操作，不能实时监测肺癌进展，早期患者不适用

活检对象	组成	优势	挑战
CTC	上皮起源的有核细胞	肿瘤细胞的高特异性，直接定量分析分离，肿瘤细胞的形态学、分子和进一步生物学分析	分离肿瘤细胞的灵敏度和特异度相对较低（技术挑战）
ctDNA	单链或双链DNA	检测DNA改变（体细胞突变、插入和删除、拷贝数改变、基因融合）的高灵敏度	很难区分ctDNA和来自正常细胞的循环DNA，没有功能分析
外泌体	蛋白质，非编码RNA，mRNA，以及单链或双链DNA	RNA分析（miRNA、mRNA、长编码RNA、RNA特异性变体、RNA表达），作为载体用于药物递送	难以区分肿瘤来源的外显体和正常细胞来源的外显体，提取困难

活检对象	组成	优势	挑战
CTC	上皮起源的有核细胞	肿瘤细胞的高特异性，直接定量分析分离，肿瘤细胞的形态学、分子和进一步生物学分析	分离肿瘤细胞的灵敏度和特异度相对较低（技术挑战）
ctDNA	单链或双链DNA	检测DNA改变（体细胞突变、插入和删除、拷贝数改变、基因融合）的高灵敏度	很难区分ctDNA和来自正常细胞的循环DNA，没有功能分析
外泌体	蛋白质，非编码RNA，mRNA，以及单链或双链DNA	RNA分析（miRNA、mRNA、长编码RNA、RNA特异性变体、RNA表达），作为载体用于药物递送	难以区分肿瘤来源的外显体和正常细胞来源的外显体，提取困难

Different Body Fluid Biopsies for Detecting Minimal Residual Disease in Lung Cancer: a Review of the Latest Advances

不同体液标本活检在肺癌微小残留疾病监测中的应用最新进展

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