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"Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease.

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.

SUBMITTER: Ilie M

PROVIDER: S-EPMC4216113 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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"Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease.

Ilie Marius M Hofman Véronique V Long-Mira Elodie E Selva Eric E Vignaud Jean-Michel JM Padovani Bernard B Mouroux Jérôme J Marquette Charles-Hugo CH Hofman Paul P

PloS one 20141031 10

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 ...[more]

PMID: 25360587

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Project description:Despite being a major cause of morbidity and mortality, chronic obstructive pulmonary disease (COPD) is frequently undiagnosed. Yet the burden of disease among the undiagnosed is significant, as these individuals experience symptoms, exacerbations, and excess mortality compared to those without COPD. The U.S. Preventive Services Task Force recommends against routine screening of asymptomatic individuals with spirometry. Hence, case-finding approaches are needed. A recently developed instrument, the five-item COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk questionnaire plus peak expiratory flow, demonstrates good sensitivity and specificity for distinguishing cases from control subjects and is being studied prospectively in primary care settings to determine its impact on patient outcomes. However, finding the undiagnosed is only half the battle. Mounting evidence suggests significant COPD-like respiratory burden among individuals without airflow obstruction. Many experience dyspnea, mucus production, and exacerbation events and have emphysema and airway abnormalities on computed tomographic (CT) imaging of the chest. However, it is still unclear how to best treat these individuals and which individuals go on to develop spirometric obstruction. These challenges underline the importance of defining what constitutes "early disease." A recently proposed definition characterizes early COPD as either: 1) airflow limitation, 2) compatible CT imaging abnormalities, or 3) accelerated forced expiratory volume in 1 second decline in persons younger than 50 years and with greater than a 10 pack-year smoking history. Although it is recognized that this definition does not encompass all individuals who will develop COPD, it is an attempt to identify a group of individuals with most rapid decline to better understand mechanisms of disease development and where disease-modifying interventions are most likely to be successful. Ultimately, leveraging tools such as chest CT imaging, the electronic medical record, and machine learning algorithms may aid in the identification of such individuals.

Dataset Information

"Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease.

Publications

"Sentinel" circulating tumor cells allow early diagnosis of lung cancer in patients with chronic obstructive pulmonary disease.

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