根据癌第四届症治疗发展分子诊断学美国癌症研究学会国际会议上的数据,循环肿瘤细胞(CTCs)可能是生物标志物鉴定的有希望的非侵袭性肿瘤材料来源的选择。
"基本观点是CTCs能提供病人当前疾病状态的实时信息,充当流动活组织的角色。"基因技术公司(Genentech)的高级研究助理Siminder Kaur Atwal博士说,"他们比肿瘤活组织检查的侵害性小得多,因为他们可从血液中检测,不需要外科手术。"
为了这项研究,Atwal和同事们利用刺入全身血的肿瘤细胞株,用2个生物芯片平台比较了FDA批准的细胞搜寻平台的CTC俘获效率。他们设法检测肺癌患者CTCs的表皮生长因子受体(EGFR)蛋白的表达和HER2的表达,或者转移乳腺癌患者CTCs的扩增。
在试验条件下,细胞搜寻和较新的生物芯片平台给出了相同的效率。而且,俘获效率依赖于EpCAM(上皮细胞粘附分子)的表达。
Atwal说:"这可能在从特定肿瘤中俘获CTCs中有一定限制,特别是三阴性乳腺癌。"
研究人员发现,俘获CTCs是与HER2状态、乳腺癌亚型标志物荧光定量PCR、KRAS突变检测与EGFR免疫荧光染色这样的生物标志物分析相协同的。在HER2阳性乳腺癌患者中,CTCs的HER2状态与肿瘤组织普遍相关,但是,在一个病人亚型中,HER2状态从诊断的原发性肿瘤改变了。Atwal说,这个发现表明,在一些病例中,CTCs可能给出与诊断组织不同的病人生物标志物状态的实时景象。
Atwal说,在这项技术广泛应用于临床生物标志物分析前,CTC检测与俘获的改善是必需的。进一步的研究将集中于评估对低EpCAM表达的特定肿瘤类型的不同检测与俘获方法。她说,另外,进一步研究将寻找患者肿瘤中出现的CTCs中其他可检测的生物标志物。(生物谷bioon.com)
ScienceDaily (Sep. 28, 2010) - Circulating tumor cells (CTCs) may be a promising alternative, noninvasive source of tumor materials for biomarker assessment, according to data presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development.
"The basic idea is that CTCs can provide real-time information about a patient's current disease state, acting as a 'liquid biopsy,'" said Siminder Kaur Atwal, Ph.D., senior research associate at Genentech. "They are much less invasive than tumor biopsies because they can be detected from a blood draw and don't require surgical intervention."
For this study, Atwal and colleagues compared the CTC capture efficiency of the Food and Drug Administration-approved Cell Search platform with two biochip platforms, using tumor cell lines spiked into whole blood. They tried to detect epidermal growth factor receptor (EGFR) protein expression in CTCs from patients with lung cancer and HER2 expression or amplification in CTCs in patients with metastatic breast cancer.
Under the tested conditions, CellSearch and the newer biochip platforms offered similar efficiency. Further, capture efficiency was dependent on EpCAM (epithelial cell adhesion molecule) expression.
"This may be a limitation in capturing CTCs from certain tumor types, notably triple-negative breast cancers," Atwal said.
Captured CTCs were amenable to biomarker analyses such as HER2 status, qRT-PCR for breast cancer subtype markers, KRAS mutation detection and EGFR staining by immunofluorescence, the researchers found. In patients with HER2-positive breast cancer, HER2 status in CTCs and tumor tissue generally correlated; however, in one patient subset, HER2 status changed from the primary tumor at diagnosis. This finding indicates that in some cases, CTCs may offer a real-time view of a patient's biomarker status that is different from diagnostic tissue, Atwal said.
Some improvements are necessary in CTC detection and capture before the technology can be generally useful in clinical biomarker analysis, Atwal said. Future studies will focus on evaluating different detection and capture methods with a particular emphasis on tumor types with a low EpCAM expression. In addition, future research will look for other biomarkers in CTCs to determine if they represent a patient's tumor, she said.