根據(jù)癌第四屆癥治療發(fā)展分子診斷學(xué)美國癌癥研究學(xué)會(huì)國際會(huì)議上的數(shù)據(jù),循環(huán)腫瘤細(xì)胞(CTCs)可能是生物標(biāo)志物鑒定的有希望的非侵襲性腫瘤材料來源的選擇,。
"基本觀點(diǎn)是CTCs能提供病人當(dāng)前疾病狀態(tài)的實(shí)時(shí)信息,,充當(dāng)流動(dòng)活組織的角色。"基因技術(shù)公司(Genentech)的高級(jí)研究助理Siminder Kaur Atwal博士說,,"他們比腫瘤活組織檢查的侵害性小得多,,因?yàn)樗麄兛蓮难褐袡z測(cè),,不需要外科手術(shù)。"
為了這項(xiàng)研究,,Atwal和同事們利用刺入全身血的腫瘤細(xì)胞株,,用2個(gè)生物芯片平臺(tái)比較了FDA批準(zhǔn)的細(xì)胞搜尋平臺(tái)的CTC俘獲效率。他們?cè)O(shè)法檢測(cè)肺癌患者CTCs的表皮生長因子受體(EGFR)蛋白的表達(dá)和HER2的表達(dá),,或者轉(zhuǎn)移乳腺癌患者CTCs的擴(kuò)增,。
在試驗(yàn)條件下,細(xì)胞搜尋和較新的生物芯片平臺(tái)給出了相同的效率,。而且,,俘獲效率依賴于EpCAM(上皮細(xì)胞粘附分子)的表達(dá)。
Atwal說:"這可能在從特定腫瘤中俘獲CTCs中有一定限制,,特別是三陰性乳腺癌,。"
研究人員發(fā)現(xiàn),俘獲CTCs是與HER2狀態(tài),、乳腺癌亞型標(biāo)志物熒光定量PCR,、KRAS突變檢測(cè)與EGFR免疫熒光染色這樣的生物標(biāo)志物分析相協(xié)同的。在HER2陽性乳腺癌患者中,,CTCs的HER2狀態(tài)與腫瘤組織普遍相關(guān),,但是,在一個(gè)病人亞型中,,HER2狀態(tài)從診斷的原發(fā)性腫瘤改變了,。Atwal說,這個(gè)發(fā)現(xiàn)表明,,在一些病例中,,CTCs可能給出與診斷組織不同的病人生物標(biāo)志物狀態(tài)的實(shí)時(shí)景象。
Atwal說,,在這項(xiàng)技術(shù)廣泛應(yīng)用于臨床生物標(biāo)志物分析前,,CTC檢測(cè)與俘獲的改善是必需的。進(jìn)一步的研究將集中于評(píng)估對(duì)低EpCAM表達(dá)的特定腫瘤類型的不同檢測(cè)與俘獲方法,。她說,,另外,進(jìn)一步研究將尋找患者腫瘤中出現(xiàn)的CTCs中其他可檢測(cè)的生物標(biāo)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.