Abstract
Chronic obstructive pulmonary disease (COPD) is a risk factor for lung cancer. Migration of circulating tumor cells (CTCs) into the blood stream is an early event that occurs during carcinogenesis. We aimed to examine the presence of CTCs in complement to CT-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis. The presence of CTCs was examined by an ISET filtration-enrichment technique, for 245 subjects without cancer, including 168 (68.6%) COPD patients, and 77 subjects without COPD (31.4%), including 42 control smokers and 35 non-smoking healthy individuals. CTCs were identified by cytomorphological analysis and characterized by studying their expression of epithelial and mesenchymal markers. COPD patients were monitored annually by low-dose spiral CT. CTCs were detected in 3% of COPD patients (5 out of 168 patients). The annual surveillance of the CTC-positive COPD patients by CT-scan screening detected lung nodules 1 to 4 years after CTC detection, leading to prompt surgical resection and histopathological diagnosis of early-stage lung cancer. Follow-up of the 5 patients by CT-scan and ISET 12 month after surgery showed no tumor recurrence. CTCs detected in COPD patients had a heterogeneous expression of epithelial and mesenchymal markers, which was similar to the corresponding lung tumor phenotype. No CTCs were detected in control smoking and non-smoking healthy individuals. CTCs can be detected in patients with COPD without clinically detectable lung cancer. Monitoring “sentinel” CTC-positive COPD patients may allow early diagnosis of lung cancer.
Highlights
Despite recent progress into therapeutic strategies, the overall prognosis of lung cancer remains dismal, in particular at advanced stages [1,2]
Design and patients This was a monocentric interventional, observational prospective study of patients with Chronic obstructive pulmonary disease (COPD). These patients were initially included in the experimental control group from a larger study (NCT00818558; Human Biobank, Nice, BB-0033-00025) of which the main purpose was the assessment of the presence and the frequency of circulating tumor cells (CTCs) in lung cancer patients undergoing surgery. The aim of this secondary study was to analyze the presence of CTCs in complement to computed tomography (CT)-scan in COPD patients without clinically detectable lung cancer as a first step to identify a new marker for early lung cancer diagnosis
CTCs were detected in 3% (5 out of 168) of COPD patients based on blood filtration and the cytopathological analysis of the isolated cells
Summary
Despite recent progress into therapeutic strategies, the overall prognosis of lung cancer remains dismal, in particular at advanced stages [1,2]. Complete surgical resection of early-stage tumors improves the prognosis of non-small cell lung cancer (NSCLC) patients. One reason for the poor prognosis in NSCLC patients is the absence of routine, easy to perform and low cost methods that allow detection of asymptomatic early-stage tumors. The methods used previously for early diagnosis of lung carcinoma, including biological tests using blood samples, were not conclusive or needed to be confirmed on larger cohorts [3,4,5]. The early diagnosis of lung cancer is a critical public health issue since 94 million smokers have an elevated risk of developing the disease, which remains the leading cause of death in the US [6,7]. The National Lung Screening Trial showed recently that low-dose CT screening is associated with a decrease in mortality from lung cancer of 20%
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