液体活检在肿瘤诊治中的研究进展

doi:10.3760/cma.j.issn.1673422X.2018.02.011

摘要/Abstract

摘要： 液体活检的研究主要集中在肿瘤诊断、转移监测、个体化治疗监测、疗效评估及预后判断等方面，其主要靶标包括循环肿瘤细胞、循环肿瘤DNA和外泌体等。目前，液体活检靶标已用于部分肿瘤的临床监测，取得了较好的临床效果，但仍存在诸多挑战。

关键词: 肿瘤循环细胞, DNA, 肿瘤, 肿瘤标记, 生物学, 液体活检, 外泌体

Abstract: Liquid biopsy mainly focuses on tumor diagnosis, metastasis monitoring, individualized treatment monitoring, curative effect evaluation and prognostic judgment. The main targets include circulating tumor cells, circulating tumor DNA and exosomes. At present, the liquid biopsy target has been used in the clinical monitoring of some tumors, and has good clinical results, but there are still many challenges.

Key words: Neoplasm circulating cells, DNA, neoplasm, Tumor markers, biological, Liquid biopsy, Exosome　　

邹江, 郭晓兰. 液体活检在肿瘤诊治中的研究进展[J]. 国际肿瘤学杂志, 2018, 45(2): 107-111.

ZOU Jiang, GUO Xiao-Lan. Advances of liquid biopsy in the diagnosis and treatment of tumor[J]. Journal of International Oncology, 2018, 45(2): 107-111.

参考文献

［1］ AlixPanabières C, Schwarzenbach H, Pantel K. Circulating tumor cells and circulating tumor DNA［J］. Annu Rev Med, 2012, 63: 199215. DOI: 10.1146/annurevmed062310094219. ［2］郭玮, 孙云帆, 潘柏申, 等. 循环肿瘤细胞检测及临床应用价值［J］. 中华临床实验室管理电子杂志, 2014, 2(3): 179184. DOI: 10.3877/cma.j.issn.20955820.03.011. ［3］ AlixPanabières C, Pantel K. Clinical applications of circulating tumor cells and circulating tumor DNA as liquid biopsy［J］. Cancer Discov, 2016, 6(5): 479491. DOI: 10.1158/21598290.CD151483. ［4］ Masuda T, Hayashi N, Iguchi T, et al. Clinical and biological significance of circulating tumor cells in cancer［J］. Mol Oncol, 2016, 10(3): 408417. DOI: 10.1016/j.molonc.2016.01.010. ［5］ Wu T, Cheng B, Fu L. Clinical applications of circulating tumor cells in pharmacotherapy: challenges and perspectives［J］. Mol Pharmacol, 2017, 92(3): 232239. DOI: 10.1124/mol.116.108142. ［6］ Yu Y, Chen Z, Dong J, et al. Folate receptorpositive circulating tumor cells as a novel diagnostic biomarker in nonsmall cell lung cancer［J］. Transl Oncol, 2013, 6(6): 697702. ［7］ Hegemann M, Stenzl A, Bedke J, et al. Liquid biopsy: ready to guide therapy in advanced prostate cancer?［J］. BJU Int, 2016, 118(6): 855863. DOI: 10.1111/bju.13586. ［8］ Bidard FC, Peeters DJ, Fehm T, et al. Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data［J］. Lancet Oncol, 2014, 15(4): 406414. DOI: 10.1016/S14702045(14)700695. ［9］ Janni WJ, Rack B, Terstappen LW, et al. Pooled analysis of the prognostic relevance of circulating tumor cells in primary breast cancer［J］. Clin Cancer Res, 2016, 22(10): 25832593. DOI: 10.1158/10780432.CCR151603. ［10］ Antonarakis ES, Lu C, Wang H, et al. ARV7 and resistance to enzalutamide and abiraterone in prostate cancer［J］. N Engl J Med, 2014, 371(11): 10281038. DOI: 10.1056/NEJMoa1315815. ［11］ Messaritakis I, Politaki E, Plataki M, et al. Heterogeneity of circulating tumor cells (CTCs) in patients with recurrent small cell lung cancer (SCLC) treated with pazopanib［J］. Lung Cancer, 2017, 104: 1623. DOI: 10.1016/j.lungcan.2016.12.008. ［12］ Huang MY, Tsai HL, Huang JJ, et al. Clinical implications and future perspectives of circulating tumor cells and biomarkers in clinical outcomes of colorectal cancer［J］. Transl Oncol, 2016, 9(4): 340347. DOI: 10.1016/j.tranon.2016.06.006. ［13］ Trapp EK, Majunke L, Zill B, et al. LKB1 prooncogenic activity triggers cell survival in circulating tumor cells［J］. Mol Oncol, 2017, 11(11): 15081526. DOI: 10.1002/18780261.12111. ［14］ Scher HI, Heller G, Molina A, et al. Circulating tumor cell biomarker panel as an individuallevel surrogate for survival in metastatic castrationresistant prostate cancer［J］. J Clin Oncol, 2015, 33(12): 13481355. DOI: 10.1200/JCO.2014.55.3487. ［15］ Li Y, Gong J, Zhang Q, et al. Dynamic monitoring of circulating tumour cells to evaluate therapeutic efficacy in advanced gastric cancer［J］. Br J Cancer, 2016, 114(2): 138145. DOI: 10.1038/bjc.2015.417. ［16］ Lu CY, Tsai HL, Uen YH, et al. Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage Ⅲ colon cancer［J］. Br J Cancer, 2013, 108(4): 791797. DOI: 10.1038/bjc.2012.595. ［17］ Aceto N, Bardia A, Miyamoto DT, et al. Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis［J］. Cell, 2014, 158(5): 11101122. DOI: 10.1016/j.cell.2014.07.013. ［18］ Mitra A, Mishra L, Li S. EMT, CTCs and CSCs in tumor relapse and drugresistance［J］. Oncotarget, 2015, 6(13): 1069710711. DOI: 10.18632/oncotarget.4037. ［19］ Fiorelli A, Accardo M, Carelli E, et al. Circulating tumor cells in diagnosing lung cancer: clinical and morphologic analysis［J］. Ann Thorac Surg, 2015, 99(6): 18991905. DOI: 10.1016/j.athoracsur.2014.11.049. ［20］ Diaz LA Jr, Bardelli A. Liquid biopsies: genotyping circulating tumor DNA［J］. J Clin Oncol, 2014, 32(6): 579586. DOI: 10.1200/JCO.2012.45.2011. ［21］ Heitzer E, Ulz P, Geigl JB. Circulating tumor DNA as a liquid biopsy for cancer［J］. Clin Chem, 2015, 61(1): 112123. DOI: 10.1373/clinchem.2014.222679. ［22］ Zhang W, Xia W, Lv Z, et al. Liquid biopsy for cancer: circulating tumor cells, circulating free DNA or exosomes?［J］. Cell Physiol Biochem, 2017, 41(2): 755768. DOI: 10.1159/000458736. ［23］ Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early and latestage human malignancies［J］. Sci Transl Med, 2014, 6(224): 224ra24. DOI: 10.1126/scitranslmed.3007094. ［24］ Dawson SJ, Tsui DW, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer［J］. N Engl J Med, 2013, 368(13): 11991209. DOI: 10.1056/NEJMoa1213261. ［25］ Romero D. Breast cancer: tracking ctDNA to evaluate relapse risk［J］. Nat Rev Clin Oncol, 2015, 12(11): 624. DOI: 10.1038/nrclinonc.2015.159. ［26］ Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to antiEGFR therapy in colorectal cancer［J］. Nature, 2012, 486(7404): 532536. DOI: 10.1038/nature11156. ［27］ Reinert T, Schler LV, Thomsen R, et al. Analysis of circulating tumour DNA to monitor disease burden following colorectal cancer surgery［J］. Gut, 2016, 65(4): 625634. DOI: 10.1136/gutjnl2014308859. ［28］ Diehl F, Schmidt K, Choti MA, et al. Circulating mutant DNA to assess tumor dynamics［J］. Nat Med, 2008, 14(9): 985990. DOI: 10.1038/nm.1789. ［29］ Calapre L, Warburton L, Millward M, et al. Circulating tumour DNA (ctDNA) as a liquid biopsy for melanoma［J］. Cancer Lett, 2017, 404: 6269. DOI: 10.1016/j.canlet.2017.06.030. ［30］ Murtaza M, Dawson SJ, Tsui DW, et al. Noninvasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA［J］. Nature, 2013, 497(7447): 108112. DOI: 10.1038/nature12065. ［31］ Oxnard GR, Paweletz CP, Kuang Y, et al. Noninvasive detection of response and resistance in EGFRmutant lung cancer using quantitative nextgeneration genotyping of cellfree plasma DNA［J］. Clin Cancer Res, 2014, 20(6): 16981705. DOI: 10.1158/10780432.CCR132482. ［32］ Xu B, Krie A, De P, et al. Utilizing tumor and plasma liquid biopsy in treatment decision making for an estrogen receptorpositive advanced breast cancer patient［J］. Cureus, 2017, 9(6): e1408. DOI: 10.7759/cureus.1408. ［33］ Tan CR, Zhou L, ElDeiry WS. Circulating tumor cells versus circulating tumor DNA in colorectal cancer: pros and cons［J］. Curr Colorectal Cancer Rep, 2016, 12(3): 151161. DOI: 10.1007/s118880160320y. ［34］ Kuderer NM, Burton KA, Blau S, et al. Comparison of 2 commercially available nextgeneration sequencing platforms in oncology［J］. JAMA Oncol, 2017, 3(7): 996998. DOI: 10.1001/jamaoncol.2016.4983. ［35］ Chae YK, Davis AA, Carneiro BA, et al. Concordance between genomic alterations assessed by nextgeneration sequencing in tumor tissue or circulating cellfree DNA［J］. Oncotarget, 2016, 7(40): 6536465373. DOI: 10.18632/oncotarget.11692. ［36］ Fais S, O′Driscoll L, Borras FE, et al. Evidencebased clinical use of nanoscale extracellular vesicles in nanomedicine［J］. ACS Nano, 2016, 10(4): 38863899. DOI: 10.1021/acsnano.5b08015. ［37］ Kowal J, Tkach M, Thery C. Biogenesis and secretion of exosomes［J］. Curr Opin Cell Biol, 2014, 29: 116125. DOI: 10.1016/j.ceb.2014.05.004. ［38］ Ludwig AK, Giebel B. Exosomes: small vesicles participating in intercellular communication［J］. Int J Biochem Cell Biol, 2012, 44(1): 1115. DOI: 10.1016/j.biocel.2011.10.005. ［39］ Colombo E, Borgiani B, Verderio C, et al. Microvesicles: novel biomarkers for neurological disorders［J］. Front Physiol, 2012, 3: 63. DOI: 10.3389/fphys.2012.00063. ［40］ GamezValero A, LozanoRamos SI, Bancu I, et al. Urinary extracellular vesicles as source of biomarkers in kidney diseases［J］. Front Immunol, 2015, 6: 6. DOI: 10.3389/fimmu.2015.00006. ［41］ Khan S, Jutzy JM, Valenzuela MM, et al. Plasmaderived exosomal survivin, a plausible biomarker for early detection of prostate cancer［J］. PLoS One, 2012, 7(10): e46737. DOI: 10.1371/journal.pone.0046737. ［42］ Melo SA, Luecke LB, Kahlert C, et al. Glypican1 identifies cancer exosomes and detects early pancreatic cancer［J］. Nature, 2015, 523(7559): 177182. DOI: 10.1038/nature14581. ［43］ Logozzi M, De Milito A, Lugini L, et al. High levels of exosomes expressing CD63 and caveolin1 in plasma of melanoma patients［J］. PLoS One, 2009, 4(4): e5219. DOI: 10.1371/journal.pone.0005219. ［44］ Szajnik M, Derbis M, Lach M, et al. Exosomes in plasma of patients with ovarian carcinoma: potential biomarkers of tumor progression and response to therapy［J］. Gynecol Obstet (Sunnyvale), 2013, Suppl 4: 3. DOI: 10.4172/21610932.S4003. ［45］ Ogorevc E, KraljIglic V, Veranic P. The role of extracellular vesicles in phenotypic cancer transformation［J］. Radiol Oncol, 2013, 47(3): 197205. DOI: 10.2478/raon20130037. ［46］ Campanella C, Rappa F, Sciumè C, et al. Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery［J］. Cancer, 2015, 121(18): 32303239. DOI: 10.1002/cncr.29499.

[1]	刘娜, 寇介丽, 杨枫, 刘桃桃, 李丹萍, 韩君蕊, 杨立洲. 血清miR-106b-5p、miR-760联合低剂量螺旋CT诊断早期肺癌的临床价值[J]. 国际肿瘤学杂志, 2024, 51(6): 321-325.
[2]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[3]	袁健, 黄燕华. Hp-IgG抗体联合血清DKK1、sB7-H3对早期胃癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(6): 338-343.
[4]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[5]	郭泽浩, 张俊旺. PFDN及其亚基在肿瘤发生发展中的作用[J]. 国际肿瘤学杂志, 2024, 51(6): 350-353.
[6]	张百红, 岳红云. 新作用机制的抗肿瘤药物进展[J]. 国际肿瘤学杂志, 2024, 51(6): 354-358.
[7]	许凤琳, 吴刚. EBV在鼻咽癌肿瘤免疫微环境和免疫治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 359-363.
[8]	王盈, 刘楠, 郭兵. 抗体药物偶联物在转移性乳腺癌治疗中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 364-369.
[9]	张蕊, 褚衍六. 基于FIT与肠道菌群的结直肠癌风险评估模型的研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 370-375.
[10]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[11]	王丽, 刘志华, 杨伟洪, 蒋凤莲, 李全泳, 宋浩杰, 鞠文东. ROS1突变肺腺鳞癌合并脑梗死为主要表现的Trousseau综合征1例[J]. 国际肿瘤学杂志, 2024, 51(6): 382-384.
[12]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[13]	杨琳, 路宁, 温华, 张明鑫, 朱琳. 炎症负荷指数与胃癌临床关系研究[J]. 国际肿瘤学杂志, 2024, 51(5): 274-279.
[14]	王俊毅, 洪楷彬, 纪荣佳, 陈大朝. 癌结节对结直肠癌根治性切除术后肝转移的影响[J]. 国际肿瘤学杂志, 2024, 51(5): 280-285.
[15]	张宁宁, 杨哲, 檀丽梅, 李振宁, 王迪, 魏永志. 宫颈细胞DNA倍体分析联合B7-H4和PKCδ对宫颈癌的诊断价值[J]. 国际肿瘤学杂志, 2024, 51(5): 286-291.