Rishindra M Reddy1, Vasudha Murlidhar2, Lili Zhao3, Svetlana Grabauskiene4, Zhuo Zhang2, Nithya Ramnath5, Jules Lin4, Andrew C Chang4, Phillip Carrott4, William Lynch4, Mark B Orringer4, David G Beer4, Sunitha Nagrath2. 1. Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan. Electronic address: reddyrm@med.umich.edu. 2. Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan. 3. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan. 4. Section of Thoracic Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan. 5. Division of Hematology/Oncology, Department of Medicine, University of Michigan, Ann Arbor, Michigan.
Abstract
OBJECTIVE: To identify circulating tumor cells (CTCs) in the blood of patients with early-stage lung cancer and to show that sampling pulmonary vein (PV) blood using microfluidic chip technology will yield significantly more CTCs. Improving early detection of lung cancer is critical to improving lung cancer survival. Reproducible detection of CTCs is limited currently in early stage tumors. METHODS: Patients undergoing pulmonary resection had PV blood drawn before resection. Peripheral blood was sampled at preoperative, intraoperative, and postoperative times. Samples were analyzed on microfluidic chips using antibody-based capture. RESULTS: A total of 32 patients with primary lung cancer were evaluated. Twenty patients had 1 or more CTCs detected in at least 1 sample (62.5%). The mean number of CTCs from peripheral vein sources at the preoperative, intraoperative, and postoperative time points was 1.3, 1.9, and 0.6 respectively. The average number of CTCs in the PV was 340.0 (range, 0.0-5422.50; P > .01). When PV CTCs were present, the number of CTCs was correlated with pathological tumor size (P = .0236). The number of PV CTCs was not correlated with any other clinical feature (eg, smoking status, preoperative or postoperative stage). Furthermore, the number of PV CTCs was significantly higher when preoperative bronchoscopic biopsy was performed, compared with computed tomography-guided biopsy (P = .0311). Seven patients had evidence of CTC clusters, or microemboli. CONCLUSIONS: With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs.
OBJECTIVE: To identify circulating tumor cells (CTCs) in the blood of patients with early-stage lung cancer and to show that sampling pulmonary vein (PV) blood using microfluidic chip technology will yield significantly more CTCs. Improving early detection of lung cancer is critical to improving lung cancer survival. Reproducible detection of CTCs is limited currently in early stage tumors. METHODS:Patients undergoing pulmonary resection had PV blood drawn before resection. Peripheral blood was sampled at preoperative, intraoperative, and postoperative times. Samples were analyzed on microfluidic chips using antibody-based capture. RESULTS: A total of 32 patients with primary lung cancer were evaluated. Twenty patients had 1 or more CTCs detected in at least 1 sample (62.5%). The mean number of CTCs from peripheral vein sources at the preoperative, intraoperative, and postoperative time points was 1.3, 1.9, and 0.6 respectively. The average number of CTCs in the PV was 340.0 (range, 0.0-5422.50; P > .01). When PV CTCs were present, the number of CTCs was correlated with pathological tumor size (P = .0236). The number of PV CTCs was not correlated with any other clinical feature (eg, smoking status, preoperative or postoperative stage). Furthermore, the number of PV CTCs was significantly higher when preoperative bronchoscopic biopsy was performed, compared with computed tomography-guided biopsy (P = .0311). Seven patients had evidence of CTC clusters, or microemboli. CONCLUSIONS: With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs.
Authors: Vasudha Murlidhar; Rishindra M Reddy; Shamileh Fouladdel; Lili Zhao; Martin K Ishikawa; Svetlana Grabauskiene; Zhuo Zhang; Jules Lin; Andrew C Chang; Philip Carrott; William R Lynch; Mark B Orringer; Chandan Kumar-Sinha; Nallasivam Palanisamy; David G Beer; Max S Wicha; Nithya Ramnath; Ebrahim Azizi; Sunitha Nagrath Journal: Cancer Res Date: 2017-07-17 Impact factor: 12.701
Authors: Marco Calandri; Giulia Siravegna; Andrea Veltri; Bruno C Odisio; Steven M Yevich; Giuseppe Stranieri; Carlo Gazzera; Scott Kopetz; Paolo Fonio; Sanjay Gupta; Alberto Bardelli Journal: Eur Radiol Date: 2020-03-19 Impact factor: 5.315
Authors: Jussuf T Kaifi; Guangfu Li; Gary Clawson; Eric T Kimchi; Kevin F Staveley-O'Carroll Journal: Cancer Biol Ther Date: 2016-04-05 Impact factor: 4.742