评估细胞表面波形蛋白阳性循环肿瘤细胞作为肺癌诊断生物标志物的作用
Evaluation of Cell Surface Vimentin Positive Circulating Tumor Cells as a Diagnostic Biomarker for Lung Cancer.
作者信息
Xie Xiaohong, Wang Liqiang, Wang Xinni, Fan Wan-Hung, Qin Yinyin, Lin Xinqing, Xie Zhanhong, Liu Ming, Ouyang Ming, Li Shiyue, Zhou Chengzhi
机构信息
Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Clinical Medical Affairs, Hangzhou Watson Biotech, Hangzhou, China.
出版信息
Front Oncol. 2021 May 14;11:672687. doi: 10.3389/fonc.2021.672687. eCollection 2021.
BACKGROUND
Circulating tumor cells (CTCs) represent a collection of heterogeneous cells. Studies have shown epithelial CTCs and folate receptor (FR) positive CTCs could be used as diagnostic biomarkers for lung cancer (LC). This study aimed to determine whether cell surface vimentin (CSV) positive CTCs could be used as a biomarker for LC as well.
METHODS
78 treatment-naïve non-small-cell lung cancer (NSCLC) patients, 21 patients with benign lung diseases (BLD) and 9 healthy donors (HD) were enrolled in this study. CTC detection was performed using CytoSorter mesenchymal CTC kit (CSV). The correlation between CSV positive CTCs (CSV-CTCs) and LC patients' clinicopathological characteristics would be evaluated, and diagnostic performances of CSV-CTCs and serum tumor markers for LC would be compared.
RESULTS
CTC detection rates (average CTC count: range) in LC patients, patients with BLD and HD were 83.33% (2.47: 0-8), 47.62% (0.5: 0-3) and 0% (0: 0), respectively. CSV-CTCs could be used to differentiate LC patients from the patients with BLD and HD ( < 0.0001). CSV-CTCs were correlated with cancer stage, lymph node involvement and distant metastasis ( = 0.0062, 0.0014 and 0.0021, respectively). With a CTC cut-off value of 2, CSV-CTCs would have a sensitivity and specificity of 0.67 and 0.87, respectively, for diagnosing LC. CSV-CTC positive rates showed statistical differences among HD, BLD patients and LC patients at different cancer stages ( < 0.0001). Furthermore, CSV-CTC positive rates were positively correlated with tumor size, lymph node involvement and distant metastasis ( = 0.0163, 0.0196 and 0.03, respectively). CSV-CTCs had a better diagnostic performance than serum tumor makers, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125) and CA153.
CONCLUSION
When CTC cut-off is set to 2 CTCs per 7.5 mL of blood, CSV-CTCs can be considered as an acceptable biomarker for diagnosing LC with a sensitivity and specificity of 0.67 and 0.87, respectively.
背景
循环肿瘤细胞（CTC）是一组异质性细胞。研究表明，上皮性CTC和叶酸受体（FR）阳性CTC可作为肺癌（LC）的诊断生物标志物。本研究旨在确定细胞表面波形蛋白（CSV）阳性CTC是否也可作为LC的生物标志物。
方法
本研究纳入了78例未经治疗的非小细胞肺癌（NSCLC）患者、21例良性肺疾病（BLD）患者和9名健康供者（HD）。使用CytoSorter间充质CTC试剂盒（CSV）进行CTC检测。评估CSV阳性CTC（CSV-CTC）与LC患者临床病理特征之间的相关性，并比较CSV-CTC和血清肿瘤标志物对LC的诊断性能。
结果
LC患者、BLD患者和HD的CTC检测率（平均CTC计数：范围）分别为83.33%（2.47：0-8）、47.62%（0.5：0-3）和0%（0：0）。CSV-CTC可用于区分LC患者与BLD患者和HD（<0.0001）。CSV-CTC与癌症分期、淋巴结受累和远处转移相关（分别为=0.0062、0.0014和0.0021）。当CTC临界值设定为2时，CSV-CTC诊断LC的敏感性和特异性分别为0.67和0.87。CSV-CTC阳性率在HD、BLD患者和不同癌症分期的LC患者之间存在统计学差异（<0.0001）。此外，CSV-CTC阳性率与肿瘤大小、淋巴结受累和远处转移呈正相关（分别为=0.0163、0.0196和0.03）。CSV-CTC的诊断性能优于血清肿瘤标志物，如癌胚抗原（CEA）、神经元特异性烯醇化酶（NSE）、癌抗原125（CA125）和CA153。
结论
当将每7.5 mL血液中CTC临界值设定为2个CTC时，CSV-CTC可被视为诊断LC的可接受生物标志物，其敏感性和特异性分别为0.67和0.87。
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