Abstract
BackgroundCirculating 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.Methods78 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.ResultsCTC 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.ConclusionWhen 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.
Highlights
Lung cancer (LC) is the most common cancer and the leading cause of cancer-related deaths both worldwide and in China [1, 2]
A significant difference of cell surface vimentin (CSV)-Circulating tumor cells (CTCs) was found among LC patients, patients with benign lung diseases (BLD) and healthy donors (HD) (P < 0.0001, Figure 1B)
If LC patients were broken-down by stage, significant differences of CSV-CTCs were still found between BLD patients and stage I, II, III or IV LC patients (P = 0.0167, 0.0307, 0.0014, or < 0.0001, Figure 1C), indicating that CSVCTCs could be used as a biomarker to distinguish LC patients from the patients with BLD and HD. 9 out of 10 patients with BLD who were found to have CSV positive cells had either inflammation diseases, fibrosis or other lung infection conditions
Summary
Lung cancer (LC) is the most common cancer and the leading cause of cancer-related deaths both worldwide and in China [1, 2]. There were approximately 787,000 newly diagnosed cases and 631,000 deaths for LC in 2015 in China [3]. Diagnostic and treatment modalities for LC have an enormous progress in recent years, most LC patients still have a poor prognosis with a 5‐year survival rate ranging from 4-17% depending on cancer stage and regional differences [4]. “Early detection, early treatment” means that patients would have a better treatment strategy and survival outcome if the tumors were diagnosed earlier [5]. 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
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