肺癌循环肿瘤细胞的临床意义

doi:10.11904/j.issn.1002-3070.2016.04.015

摘要/Abstract

摘要： 转移是导致肺癌患者死亡的首因,而循环肿瘤细胞(Circulating tumor cells,CTCs)在形成远处转移过程中起关键作用。近年研究显示,CTCs可能成为肺癌诊疗的新兴标志物及治疗新靶点,本文从诊断与临床分期、转移与复发、个体化治疗与预后等方面阐述肺癌CTCs的临床意义,以期为肺癌治疗提供新策略。

关键词: 循环肿瘤细胞, 肺癌, 转移, 免疫系统

Abstract: Metastasis is the leading cause of death in patients with lung cancer.Circulating tumor cells(CTCs)play a key role in the process of distant metastasis.In recent years,research results have shown that CTCs may become a emerging marker and new target in the treatment of lung cancer.In this article,we elaborate the clinical significance of CTCs in lung cancer from the way of diagnosis and clinical staging,metastasis and recurrence,individual treatment and prognosis and so on,so that we can provide a new direction for the treatment of lung cancer.

Key words: Circulating tumor cells, Lung cancer, Metastasis, Immune system

中图分类号:

R734.2

罗斌,施奇惠,刘嘉湘综述,田建辉审校. 肺癌循环肿瘤细胞的临床意义[J]. 实用肿瘤学杂志, 2016, 30(4): 370-374.

LUO Bin ,SHI Qihui ,LIU Jiaxiang ,TIAN Jianhui. The clinical significance of circulating tumor cells in lung cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2016, 30(4): 370-374.

参考文献

1 Siegel RL,Miller KD,Jemal A.Cancer statistics,2015[J].CA,2015,65(1):5-29.
2 Chen W,Zheng R,Zeng H,et al.Annual report on status of cancer in China,2011[J].Chin J Cancer Res,2015,27(1):2-12.
3 Hanahan D,Weinberg RA.Hallmarks of cancer:The next generation[J].Cell,2011,144(5):646-674.
4 Ashworth TR.A case of cancer in which cells similar to those in the tumours were seen in the blood after death[J].Med J Austral,1869,14:146-149.
5 Budd GT,Cristofanilli M,Ellis MJ,et al.Circulating tumor cells versus imaging predicting overall survival in metastatic breast cancer[J].Clin Cancer Res,2006,12(21):6403-6409.
6 Cohen SJ,Punt CJ,lannotti N,et al.Relationship of circulating tumor cells to tumor response,progression-free survival,and overall survival in patients with metastatic colorectal cancer[J].J Clin Oncol,2008,26(19):3213-3221.
7 de Bono JS,Scher HI,Montgomery RB,et al.Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer[J].Clin Cancer Res,2008,14(19):6302-6309.
8 Matsusaka SJ,Chin K,Ognra MJ,et al.Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer[J].Cancer Sci,2010,101(4):1067-1071.
9 Hou JM,Krebs MG,Lancashire LJ,et al.Clinical signifcance and molecular characteristics of circulating tumor cells and circulating tumor microemboli in patients with small-cell lung cancer[J].J Clin Oncol,2012,30(5):525-532.
10 Mandrekar SJ,Qi Y,Hillman SL,et al.Endpoints in phase II trials for advanced non-small cell lung cancer[J].J Thorac Oncol,2010,5(1):3-9.
11 Franco R,Cantile M,Marino FZ,et al.Circulating tumor cells as emerging tumor biomarkers in lung cancer[J].J Thorac Dis,2012,4(5):438-439.
12 Yu N,Zhou J,Cui F,et al.Circulating tumor cells in lung cancer:Detection methods and clinical applications[J].Lung,2015,193(2):157-171.
13 Allard WJ,Matera J,Miller MC,et al.Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with non-malignant diseases[J].Clin Cancer Res,2004,10(20):6897-6904.
14 Hou JM,Krebs M,Ward T,et al.Circulating tumor cells as a window on metastasis biology in lung cancer[J].Am J Pathol,2011,178(3):989-996.
15 张百红,岳红云.肿瘤转移理论[J].现代肿瘤医学,2015,23(1):128-130.
16 Yoon HJ,Kozminsky M,Nagrath S.Emerging role of nanomaterials in circulating tumor cell isolation and analysis[J].ACS Nano,2014,8(3):1995-2017.
17 Naito T,Tanaka F,Ono A,et al.Prognostic impact of circulating tumor cells in patients with small cell lung cancer[J].J Thorac Oncol,2012,7(3):512-519.
18 Prudkin L,Liu DD,Ozburn NC,et al.Epithelial-to-mesenchymal transition in the development and progression of adenocarcinoma and squamous cell carcinoma of the lung[J].Mod Pathol,2009,22(5):668-678.
19 付晓飞,杨之斌,殷正丰.血小板与循环肿瘤细胞[J].肿瘤,2014,34(3):286-290.
20 Heerboth S,Housman G,Leary M,et al.EMT and tumor metastasis[J].Clin Transl Oncol,2015,4:6-19.
21 Joosse SA,Gorges TM,Pantel K.Biology,detection,and clinical implications of circulating tumor cells[J].EMBO Mol Med,2015,7(1):1-11.
22 Plaks V,Koopman CD,Werb Z.Circulating tumor cells[J].Science,2013,341(6151):1186-1190.
23 Bevilacqua S,Gallo M,Franco R,et al.A"live"biopsy in a small-cell lung cancer patient by detection of circulating tumor cells[J].Lung Cancer,2009,65(1):123-125.
24 Tanaka F,Yoneda K,Kondo N.Circulating tumor cell as a diagnostic marker in primary lung cancer[J].Clin Cancer Res,2009,15(22):6980-6986.
25 陈晓霞,任胜祥,李雪飞,等.循环肿瘤细胞在肺癌诊断中的作用[C].吉林:全国肺癌学术大会,2013.
26 Maheswaran S,Sequist LV,Nagrath S,et al.Detection of mutations in EGFR in circulating lung cancer cells[J].N Engl J Med,2008,359(4):366-377.
27 De Giorgi U,Valero V,Rohren E,et al.Circulating tumor cells and [18F] fluorodeo-xyglucose positron emission tomography/computed tomography for outcome prediction in metastatic breast cancer[J].J Clin Oncol,2009,27(20):3303-3311.
28 陈燕,李虎,秦琴,等.非小细胞肺癌患者外周血循环肿瘤细胞的检测及与病理分期关系[J].临床军医杂志,2014,42(2):192-194.
29 万佳蔚,沈洪远,黄红宇,等.非小细胞肺癌患者外周血循环肿瘤细胞与临床特征关系的初步研究[J].临床与病理杂志,2015,35(1):43-47.
30 Christiansen JJ,Rajasekaran AK.Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis[J].Cancer Res,2006,66(17):8319-8326.
31 O Flaherty JD,Gray S,Richard D,et al.Circulating tumour cells,their role in metastasis and their clinical utility in lung cancer[J].Lung Cancer,2012,76(1):19-25.
32 Tanaka F,Yoneda K,Kondo N,et al.Circulating tumor cell as a diagnostic marker in primary lung cancer[J].Clin Cancer Res,2009,15(22):6980-6986.
33 Menen RS,Pinney E,Kolostova K,et al.A rapid imageable in vivo metastasis assay for circulating tumor cells[J].Anticancer Res,2011,31(10):3125-3128.
34 Krebs MG,Sloane R,Priest L,et al.Evaluation and prognostic significance of circulating tumor cells in patients with non-small-cell lung cancer[J].J Clin Oncol,2011,29(12):1556-1563.
35 周小昀,李龙芸,郝淮杰,等.外周血循环肿瘤细胞在晚期肺癌患者的预测及预后价值研究[J].癌症进展,2010,8(5):484-490.
36 Hirose T,Murata Y,Oki Y,et al.Relationship of circulating tumor cells to the effectiveness of cytotoxic chemotherapy in patients with metastatic non-small-cell lung cancer[J].Oncol Res,2012,20(2-3):131-137.
37 Hiltermann TJN,Pore MM,vanden BA,et al.Circulating tumor cells in small-cell lung cancer:a predictive and prognostic factor[J].Ann Oncol,2012,23(11):2937-2942.
38 Nieva J,Wendel M,Luttgen MS,et al.High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients:a longitudinal analysis[J].Physical Biology,2012,9(1):16004-16021.
39 田建辉,朱飞鹏,刘苓霜,等.“以人为本”建立中医药实体瘤疗效评价标准[J].上海中医药杂志,2012,46(9):3-6.
40 Whiteside TL.Immune modulation of T-cell and NK(natural killer)cell activities by TEXs(tumour-derived exosomes)[J].Biochem Soc Trans,2013,41(1):245-251.
41 Iero M,Valenti R,Huber V,et al.Tumour-released exosomes and their implications in cancer immunity[J].Cell Death Differ,2008,15(1):80-88.
42 Chen Q,Zhang XH,Massague J.Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs[J].Cancer Cell,2011,20(4):538-549.
43 Palumbo JS,Talmage KE,Massari JV,et al.Platelets and fibrin(ogen)increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells[J].Blood,2005,105(1):178-185.
44 Gil-Bernabe AM,Ferjancic S,Tlalka M,et al.Recruitment of monocytes/macrophages by tissue factor-mediated coagulation is essential for metastatic cell survival and premetastatic niche establishment in mice[J],Blood,2012,119(13):3164-3175.
45 Huh SJ,Liang S,Sharma A,et al.Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development[J].Cancer Res,2010,70(14):6071-6082.
46 Timothy AY,David L,Aurelius O,et al.Circulating tumor cells:a multifunctional biomarker[J].Clin Cancer Res,2014,20(10):2552-2568.
47 Pantel K,Alix-Panabières C.Detection methods of circulating tumor cells[J].J Thorac Dis,2012,4(5):446-447.
48 Zhang Z,Shiratsuchi H,Lin J,et al.Expansion of CTCs from early stage lung cancer patients using a microfluidic co-culture model[J].Oncotarget,2014,5(23):12383-12397.
49 Zhang Y,Tang Y,Sun S,et al.Single-cell codetection of metabolic activity,intracellular functional proteins,and genetic mutations from rare circulating tumor cells[J].Anal Chem,2015,87(19):9761-9768.

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