Evaluation of Cell Surface Vimentin Positive Circulating Tumor Cells as a Diagnostic Biomarker for Lung Cancer

被引:21
作者
Xie, Xiaohong [1 ]
Wang, Liqiang [1 ]
Wang, Xinni [1 ]
Fan, Wan-Hung [2 ]
Qin, Yinyin [1 ]
Lin, Xinqing [1 ]
Xie, Zhanhong [1 ]
Liu, Ming [1 ]
Ouyang, Ming [1 ]
Li, Shiyue [1 ]
Zhou, Chengzhi [1 ]
机构
[1] Guangzhou Med Univ, Dept Pulm & Crit Care Med, Guangzhou Inst Resp Hlth,Affiliated Hosp 1, State Key Lab Resp Dis,Natl Clin Res Ctr Resp Dis, Guangzhou, Peoples R China
[2] Hangzhou Watson Biotech, Dept Clin Med Affairs, Hangzhou, Peoples R China
关键词
circulating tumor cells; cell surface vimentin (CSV); NSCLC; cancer diagnosis; serum tumor markers;
D O I
10.3389/fonc.2021.672687
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-naive 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(R) 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 (P < 0.0001). CSV-CTCs were correlated with cancer stage, lymph node involvement and distant metastasis (P = 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 (P < 0.0001). Furthermore, CSV-CTC positive rates were positively correlated with tumor size, lymph node involvement and distant metastasis (P = 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.
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页数:11
相关论文
共 47 条
[1]   Heterogeneity in Circulating Tumor Cells: The Relevance of the Stem-Cell Subset [J].
Agnoletto, Chiara ;
Corra, Fabio ;
Minotti, Linda ;
Baldassari, Federica ;
Crudele, Francesca ;
Cook, William Joseph James ;
Di Leva, Gianpiero ;
D'Adamo, Adamo Pio ;
Gasparini, Paolo ;
Volinia, Stefano .
CANCERS, 2019, 11 (04)
[2]   EMT in cancer [J].
Brabletz, Thomas ;
Kalluri, Raghu ;
Angela Nieto, M. ;
Weinberg, Robert A. .
NATURE REVIEWS CANCER, 2018, 18 (02) :128-+
[3]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[4]   Folate Receptor-Positive Circulating Tumor Cell Detected by LT-PCR-Based Method as a Diagnostic Biomarker for Non-Small-Cell Lung Cancer [J].
Chen, Xiaoxia ;
Zhou, Fei ;
Li, Xuefei ;
Yang, Guohua ;
Zhang, Ling ;
Ren, Shengxiang ;
Zhao, Chao ;
Deng, Qinfang ;
Li, Wei ;
Gao, Guanghui ;
Li, Aiwu ;
Zhou, Caicun .
JOURNAL OF THORACIC ONCOLOGY, 2015, 10 (08) :1163-1171
[5]   Effect of circulating tumor cells combined with negative enrichment and CD45-FISH identification in diagnosis, therapy monitoring and prognosis of primary lung cancer [J].
Chen, Yang-Yang ;
Xu, Guo-Bin .
MEDICAL ONCOLOGY, 2014, 31 (12) :1-9
[6]   Early Detection of Recurrence in Patients With Locally Advanced Non-Small-Cell Lung Cancer via Circulating Tumor Cell Analysis [J].
Chinniah, Chimbu ;
Aguarin, Louise ;
Cheng, Philip ;
Decesaris, Cristina ;
Cutillo, Alicia ;
Berman, Abigail T. ;
Frick, Melissa ;
Doucette, Abigail ;
Cengel, Keith A. ;
Levin, William ;
Hahn, Stephen ;
Dorsey, Jay F. ;
Simone, Charles B., II ;
Kao, Gary D. .
CLINICAL LUNG CANCER, 2019, 20 (05) :384-+
[7]   Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer [J].
Cohen, Steven J. ;
Punt, Cornelis J. A. ;
Iannotti, Nicholas ;
Saidman, Bruce H. ;
Sabbath, Kert D. ;
Gabrail, Nashat Y. ;
Picus, Joel ;
Morse, Michael ;
Mitchell, Edith ;
Miller, M. Craig ;
Doyle, Gerald V. ;
Tissing, Henk ;
Terstappen, Leon W. M. M. ;
Meropol, Neal J. .
JOURNAL OF CLINICAL ONCOLOGY, 2008, 26 (19) :3213-3221
[8]   Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer [J].
de Bono, Johann S. ;
Scher, Howard I. ;
Montgomery, R. Bruce ;
Parker, Christopher ;
Miller, M. Craig ;
Tissing, Henk ;
Doyle, Gerald V. ;
Terstappen, Leon W. W. M. ;
Pienta, Kenneth J. ;
Raghavan, Derek .
CLINICAL CANCER RESEARCH, 2008, 14 (19) :6302-6309
[9]   Circulating Tumor Cells as a Screening and Diagnostic Marker for Early-Stage Non-Small Cell Lung Cancer [J].
Duan, Guo-Chen ;
Zhang, Xiao-Peng ;
Wang, Hui-En ;
Wang, Zhi-Kang ;
Zhang, Hua ;
Yu, Lei ;
Xue, Wen-Fei ;
Xin, Zhi-Fei ;
Hu, Zhong-Hui ;
Zhao, Qing-Tao .
ONCOTARGETS AND THERAPY, 2020, 13 :1931-1939
[10]   Circulating Tumor Cells in Diagnosing Lung Cancer: Clinical and Morphologic Analysis [J].
Fiorelli, Alfonso ;
Accardo, Marina ;
Carelli, Emanuele ;
Angioletti, Denise ;
Santini, Mario ;
Di Domenico, Marina .
ANNALS OF THORACIC SURGERY, 2015, 99 (06) :1899-1905