乳腺癌患者外周血中循环肿瘤细胞的检测及临床意义
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摘要
目的:探讨乳腺癌患者外周血中循环肿瘤细胞(circulating tumor cell,CTC)检测的临床意义。方法:应用纳米基底富集分离及免疫荧光染色方法检测CTC数目变化和CTC-Her2表达,分析CTC与临床病理特征的关系。结果:乳腺癌患者外周血中CTC的检出率明显高于乳腺良性病变(43.9%vs 0),两者比较差异有统计学意义(P<0.05)。CTC检测与乳腺癌患者年龄、肿瘤大小、组织类型、淋巴结转移及激素受体ER和PR表达无关(P>0.05)。CTC检测与脉管内查见癌栓相关(P<0.05)。组织学Her2阳性与CTC-Her2阳性具有较高的一致性。结论:CTC可能反应乳腺癌的转移能力,CTC检测可以作为判断乳腺癌预后的新指标。CTC-Her2检测可能有助于实时Her2状态的判断。
Objective:To investigate the detection of circulating tumor cell(CTC) in breast cancer and its clinical significance.Methods:Nano-basement enrichment and immunofluorescent staining were employed to detect CTC and CTC-Her2.Results:The detection rate of CTC in breast cancer was obviously higher than that in benign breast disease(43.9% vs 0).There was significant difference between breast cancer and benign breast disease(P<0.05),and it was not related to age,tumor size,histological type,lymph node metastasis and positive expression of ER and PR(P>0.05).Detection of CTC was significantly correlated with tumor emboli in blood vessels of tumor(P<0.05).Histological Her2 positive expression was obviously consistent with Her2 positive in CTC.Conclusion:CTC indicates the metastasis ability of breast cancer,and it is a new indicator to judge cancer prognosis.The detection of CTC-Her2 may help determine the real-time Her2 state.
Objective:To investigate the detection of circulating tumor cell(CTC) in breast cancer and its clinical significance.Methods:Nano-basement enrichment and immunofluorescent staining were employed to detect CTC and CTC-Her2.Results:The detection rate of CTC in breast cancer was obviously higher than that in benign breast disease(43.9% vs 0).There was significant difference between breast cancer and benign breast disease(P<0.05),and it was not related to age,tumor size,histological type,lymph node metastasis and positive expression of ER and PR(P>0.05).Detection of CTC was significantly correlated with tumor emboli in blood vessels of tumor(P<0.05).Histological Her2 positive expression was obviously consistent with Her2 positive in CTC.Conclusion:CTC indicates the metastasis ability of breast cancer,and it is a new indicator to judge cancer prognosis.The detection of CTC-Her2 may help determine the real-time Her2 state.
引文
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[27] Jordan NC,Bardia A,Wittner AB,et al.HER2 expression identifies dynamic functional states within circulating breast cancer cells[J].Nature,2016,37(7618):102-106.
[2] Torre LA,Bray F,Siegel RL,et al.Global cancer statistics[J].CA Cancer,2015,65(2):87-108.
[3] De Luca F,Rotunno G,Wittner BS,et al.Mutational analysis of single circulating tumor cells by next generation sequencing in metastatic breast cancer[J].Oncotarget,2016,7(18):26107-26119.
[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.
[5] Toyoshima K,Hayashi A,Kashiwagi M,et al.Analysis of circulating tumor cells derived from advanced gastric cancer[J].Int Cancer,2015,137(4):991-998.
[6] Pantel K,Alix-Panabieres C.Functional studies on viable circulating tumor cells[J].Clin Chem,2016,62(2):328-334.
[7] Banyspaluchowski M,Krawczyk N,Meierstiegen F,et al.Circulating tumor cells in breast cancer-current status and perspectives[J].Crit Rev Oncol Hematol,2015,97(1):22-29.
[8] Wu S,Liu S,Liu Z,et al.Classinfication of circulating tumor cells by epithelial-mesenchymal trasition markers[J].PLoS One,2015,10(4):123976-123982.
[9] Hyun KA,Lee TY,Lee SH,et al.Two-stage microfluidic chip for selective isolation of circulation tumor cells(CTCs)[J].Biosens Bioelecton,2015,15(67):86-92.
[10] Barriere G,Fici P,Gallerani G,et al.Circulating tumor cells and epithelial,mesenchymal and stemness markers:Characterization of cell subpopulations[J].Ann Transl Med,2014,2(11):109-115.
[11] Xu YM,Zheng QH.Fluid biopsy and accurate tumor care[J].Chin J Cancer Biotherapy,2016,23(5):589-594.[许扬梅,郑秋红.液体活检和肿瘤精准医疗[J].中国肿瘤生物治疗杂志,2016,23(5):589-594.]
[12] Bidard FC,Peeters DJ,Fehm T,et al.Clinical validity of circulating tumor cells in patients with metastatic breast cancer:A pooled analysis of individual patient data[J].Lancet Oncol,2014,15(4):406-414.
[13] Hamilton G,Rath B,Holzer S,et al.Second-line therapy for small cell lung:Exploring the potential role of circulating tumor cells[J].Transl Lung Cancer,2016,5(1):71-77.
[14] Kulasinghe A,Perry C,Jovanovic L,et al.Circulating tumor cells in metastatic head and neck cancers[J].Int J Cancer,2015,163 (11):2515-2523.
[15] Basse SA,Kathy G,Siobhan N,et al.Prognostic impact of vascular and lymphovascular invasion in early lung cancer[J].Asian Cardiovasc Thorac Ann,2014,22(1):55-64.
[16] Ignatiadis M,Dawson SJ.Circulating tumor cells and circulating tumor DNA for precision medicine:Dream or reality[J]?Ann Oncol,2014,25(12):2304-2313.
[17] Rack B,Schindlbeck C,Juckstock J,et al.Circulating tumor cells predict survival in early average-to-high risk breast cancer patients[J].J Natl Cancer Inst,2014,106(5):66-71.
[18] Castle J,Shaker H,Morris K,et al.The significance of circulating tumor cells in breast cancer:A review[J].Breast,2014,23(5):552-560.
[19] Gorges TM,Kuske A,Rock K,et al.Accession of tumor heterogeneity by multiplex transptome profiling of single circulating tumor cells[J].Clin Chem,2016,66(11):1504-1515.
[20] Tian XK,Li YM,Hu BG,et al.Detection and clinical significance of Cyttel circulating tumor cells in peripheral blood of patients with gastric cancer[J].Chin J Experimental Surg,2017,34(2):208-210.[田晓坤,李玉明,胡宝光,等.胃癌患者外周血Cyttel循环肿瘤细胞检测及临床意义[J].中华实验外科杂志,2017,34(2):208-210.]
[21] Uawisetwathana U,Rodpai E,Moongkarndi P.Gene expression of cytokeratin 19 and its molecular detection in human breast cancer lines[J].J Pharm Biomed Anal,2016,120(2):25-31.
[22] Wu Junxin,He Junyan,Du Kaixin,et al.Detection of circulating tumor cells in peripheral blood of patients with nasopharyngeal carcinoma and evaluate its prognostic value[J].Modern Oncology,2017,25(07):1035-1039.[吴君心,贺俊彦,杜开新,等.鼻咽癌患者外周血循环肿瘤细胞的检测及其与预后的相关性[J].现代肿瘤医学,2017,25(07):1035-1039.]
[23] Chen XX,Bai F.Single-cell analyses of circulating tumor cells[J].Cancer Biol Med,2015,12(3):184-192.
[24] He QY.Tumor heterogeneity and tumor target drug tolerance[J].Acta Pharmaceutica Sinica,2016,51(2):197-201.[何琪杨.肿瘤异质性与肿瘤靶向药物的耐药性[J].药学学报,2016,51(2):197-201.]
[25] Paoletti C,Muniz MC,Thomas DG,et al.Development of circulating tumor cell-endocrine therapy index in petients with hormone receptor-positive breast cancer[J].Clinc Cancer Res,2015,21(11):2487-2498.
[26] Zhang S,Li L,Wang T,et al.Real-time Her2 status detected on circulating tumor cells predicts different outcomes of anti-Her2 therapy in histologically Her2 positive metastatic breast cancer patients[J].BMC Cancer,2016,16(1):526-530.
[27] Jordan NC,Bardia A,Wittner AB,et al.HER2 expression identifies dynamic functional states within circulating breast cancer cells[J].Nature,2016,37(7618):102-106.