Clin Cancer Res：狩猎循环肿瘤细胞

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作者：Beyond来源：生物谷2012-10-30 10:29:06分享到： 0( {9 |5 M7 v( m0 N
关键词： 循环肿瘤细胞 转移 预后
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2012年10月30日 讯 /生物谷BIOON/ --标准样品管中7.5毫升血液用于检测转移性乳腺癌，前列腺癌，大肠癌患者的血液中循环肿瘤细胞（CTCs）是远远不够的。这些CTCs是癌症患者转移的主要原因。如果它们的特征可以被有效地研究分析，那么是可以确定最有效的治疗手段，改善患者预后的。然而，检测一类特定的细胞受到患者透析全部血液量的影响。Frank Coumans等在杂志Clinical Cancer Research上发表最新研究证实了上述观点。, k4 a& q0 s7 W

0 J! z% y; Y6 q循环肿瘤细胞（CTCs）的标准测试要用到7.5毫升的血液样品，具体是使用磁性粒子从血液中将CTC与其它组分分离开来。但是， Coumans博士发现，这种方法无法检测到到所有癌症患者体内的循环肿瘤细胞，成功率估计只有一半左右。因此，对于这些患者中，该方法是转移评价不充分可靠的指标。
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循环肿瘤细胞检测中用到几个具体指标，其中之一是上皮细胞粘附分子（EpCAM），这类粘附分子在正常血细胞中不存在。其他指标还包括细胞角蛋白和CD45，但任何白血细胞意外含有微量EpCAM和细胞角蛋白，都可能会被错误地计算成为循环肿瘤细胞。; Q: i% ?' H  V

/ T9 S: S5 J) y8 z) ]/ W研究组通过使用一种改进的CellSearch分析仪改进循环肿瘤细胞检测。然而，根据医生Coumans表示，只有这样才能检测样品中99％的CTC。但这种方法需要使用额外的技术，最好是使用新鲜血液。博士Coumans的研究是欧洲研究项目的一部分，他预计这一方法将可能进入临床测试阶段。（生物谷：Bioon.com）3 {% U% f: f7 v, g1 w! A/ j0 V

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% J; l- l' x) d4 X; G( C! p, D6 udoi:10.1158/1078-0432.CCR-12-1585
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PMID:
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& q1 j8 h" a' I" ~& A/ s9 \( J5 `Challenges in the Enumeration and Phenotyping of CTC) R6 Q9 |+ c) Z! m2 S1 O* g  [: @

) a; m8 x  S7 S/ r+ d4 u- [+ XFrank A.W. Coumans, Sjoerd T. Ligthart, Jonathan W. Uhr, and Leon W.M.M. Terstappen4 C$ S( ^* k0 Z

; L1 a( w/ N& GPurpose: Presence of circulating tumor cells (CTC) in metastatic carcinoma is associated with poor survival. Phenotyping and genotyping of CTC may permit “real-time” treatment decisions, provided CTCs are available for examination. Here, we investigate what is needed to detect CTC in all patients.6 v; O- E9 R* g6 Q/ R- Q6 G1 L
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Experimental Design: CTCs enumerated in 7.5 mL of blood together with survival from 836 patients with metastatic breast, colorectal, and prostate cancer were used to predict the CTC concentration in the 42% of these patients in whom no CTCs were found and to establish the relation of concentration of CTCs with survival. Influence of different CTC definitions were investigated by automated cell recognition and a flow cytometric assay without an enrichment or permeabilization step.
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% s, w' Y+ k2 L( p2 F9 M; p) WResults: A log-logistic regression of the log of CTC yielded a good fit to the CTC frequency distribution. Extrapolation of the blood volume to 5 L predicted that 99% of patients had at least one CTC before therapy initiation. Survival of patients with EpCAM+, cytokeratin+, CD45? nucleated CTCs is reduced by 6.6 months for each 10-fold CTC increase. Using flow cytometry, the potential three-fold recovery improvement is not sufficient to detect CTC in all patients in 7.5 mL of blood.
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Conclusions: EpCAM+, cytokeratin+, CD45? nucleated CTCs are present in all patients with metastatic breast, prostate, and colorectal cancer and their frequency is proportional to survival. To serve as a liquid biopsy for the majority of patients, a substantial improvement of CTC yield is needed, which can only be achieved by a dramatic increase in sample volume.