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Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.
Authors
Ebrahim Azizi
David G Beer
+17 more
Philip Carrott
Andrew C Chang
Shamileh Fouladdel
Svetlana Grabauskiene
Martin K Ishikawa
Chandan Kumar-Sinha
Jules Lin
William R Lynch
Vasudha Murlidhar
Sunitha Nagrath
Mark B Orringer
Nallasivam Palanisamy
Nithya Ramnath
Rishindra M Reddy
Max S Wicha
Zhuo Zhang
Lili Zhao
Publication date
15 September 2017
Publisher
Henry Ford Health System Scholarly Commons
Abstract
Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe (P \u3c 0.0001) and intraoperative Pe (P \u3c 0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long-term surveillance indicated that presence of clusters in preoperative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR
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Last time updated on 30/10/2019