Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of advanced lung adenocarcinoma patients
Prognostic value of cytokeratin-7 mRNA expression in peripheral whole blood of advanced lung adenocarcinoma patients
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DOI：
10.1007/s13402-015-0238-4
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发表时间：
2015-10-01
影响因子：
6.6
通讯作者：
Cufer, Tanja
中科院分区：
文献类型：
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作者：
Koren, Ana;Sodja, Eva;Cufer, Tanja
背景外周血中循环肿瘤细胞（CTC）的稀有性要求应用灵敏的技术对其进行检测。本研究的目的是（i）首先确定细胞角蛋白-7（KRT 7）mRNA表达水平对使用加标肺腺癌（AC）衍生的A549细胞进行CTC分子检测的敏感性，以及（ii）评估外周全血中KRT 7 mRNA表达对接受一线铂类药物治疗的晚期肺AC患者的治疗反应和预后的影响。方法在将A549细胞掺入从健康供体获得的全血样品中之前，对A549细胞进行显微操作。此外，在一线铂类化疗开始前，在PAXgene采血管中采集了65例肺AC患者的全血样本。结果通过加标实验，我们发现在2.5ml全血中检测单个A549肿瘤细胞是可行的，并且KRT 7 mRNA水平与加标肿瘤细胞的数量呈线性相关，具有很高的重复性。在肺AC患者中，化疗反应率，无进展生存期或总生存期和KRT 7 mRNA水平无显着差异被发现。结论我们的数据表明，KRT 7 mRNA表达RT-qPCR测量作为一个敏感的方法，为KRT 7阳性CTC样A549细胞在外周血中的分子检测。KRT 7 mRNA水平与晚期肺AC患者的化疗反应或生存率无显著相关性。需要进一步的研究来确定化疗后全血中KRT 7 mRNA表达的可能临床意义。
Background The rarity of circulating tumour cells (CTCs) in peripheral blood requires the application of sensitive techniques for their detection. The aim of our study was to (i) first determine the sensitivity of cytokeratin-7 (KRT7) mRNA expression levels for the molecular detection of CTCs using spiked-in lung adenocarcinoma (AC)-derived A549 cells and (ii) evaluate the impact of KRT7 mRNA expression in peripheral whole blood on the response to treatment and prognosis of patients with advanced lung AC who were treated with first-line platinum-based chemotherapy.Methods A549 cells were micro-manipulated before being spiked into whole blood samples obtained from healthy donors. Additionally, whole blood samples from 65 lung AC patients were collected in PAXgene blood tubes before the start of first-line platinum-based chemotherapy. KRT7 mRNA expression was measured using RT-qPCR.Results Through the spike-in experiment we found that it is feasible to detect a single A549 tumour cell in 2.5 ml whole blood and that the KRT7 mRNA levels were linearly correlated with the number of spiked-in tumour cells with a high reproducibility. In lung AC patients, no significant differences in response rate to chemotherapy, progression-free survival or overall survival and KRT7 mRNA levels were found.Conclusions Our data show that KRT7 mRNA expression measured by RT-qPCR serves as a sensitive approach for the molecular detection of KRT7-positive CTC-resembling A549 cells in peripheral whole blood. The KRT7 mRNA levels measured were not significantly associated with the response to chemotherapy or the survival of patients with advanced lung AC. Additional studies are required to establish the possible clinical significance of KRT7 mRNA expression in whole blood after chemotherapy.