Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case–control study

Cirincione, Rosalia; Lintas, Carla; Conte, Davide; Mariani, Luigi; Roz, Luca; Vignola, Antonio M.; Pastorino, Ugo; Sozzi, Gabriella

doi:10.1002/ijc.21473

Cited by 46 publications

(30 citation statements)

References 23 publications

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“…At the present time (after 3 years of follow-up), this individual is alive and disease-free. Only a few studies are available on RASSF1A in cancer-free individuals with discordant data: earlier articles report 3% to 4% hypermethylation frequency (7,11), with 30.8% as a peak in a single report (8); recent data show a lower methylation rate (31), in keeping with our findings. NORE1A was not studied before in cancer-free individuals (32,33).…”

Section: Discussionsupporting

confidence: 86%

Molecular Alterations in Spontaneous Sputum of Cancer-Free Heavy Smokers: Results from a Large Screening Program

Baryshnikova

Destro

Infante³

et al. 2008

Clinical Cancer Research

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Purpose: The high mortality rate for lung cancer is likely to be reduced by the development of a panel of sensitive biological markers able to identify early-stage lung cancers or subjects at high risk. The aim of this study was to establish the frequency of K-ras and p53 mutations and p16 INK4A, RASSF1A, and NORE1A hypermethylation in sputum of a large cohort of cancer-free heavy smokers and to assess whether these markers are suitable for a routine use in the clinical practice for the early diagnosis of pulmonary cancer. Experimental Design: Sputum samples were collected from 820 heavy smokers. Inclusion criteria consisted of radiologic and cytologic absence of pulmonary lesions, age at least 60 years, male gender, and a smoking history of at least 20 pack-years. Results: The analysis identified 56 individuals (6.9%) with one molecular alteration. p53 mutation and p16 INK4A, RASSF1A, and NORE1A methylation frequencies were 1.9%, 5.1%, 0.8%, and 1.0 %, respectively; no K-ras mutations were found. One patient with p53 mutations was diagnosed with an early-stage lung cancer after 3-years of follow-up. The molecular analysis of bronchoscopy samples confirmed in half of the cases alterations present in sputum without revealing additional molecular changes. Conclusions: Genetic and epigenetic abnormalities can be detected in cancer-free heavy smokers. Although the predictive value of the cancer risk is still to be established as it requires not less than 5 years of follow-up, p53 and p16INK4A are more promising candidates than K-ras, RASSF1A, and NORE1A for the pulmonary molecular screening of heavy smokers healthy individuals.Lung cancer is one of the most frequent malignancies worldwide and the leading cause of cancer-related death in male (1). The increasing incidence of non -small cell lung cancer (NSCLC) in the industrialized countries is mainly due to the expanding consumption of tobacco, directly associated with NSCLC etiology. Epidemiologic studies show that f85% of the cases of NSCLC arise in current or former smokers (2). Interestingly, 50% of all newly diagnosed lung cancers occur in people who stopped smoking by at least 5 years, supporting that the damage to the respiratory epithelium is persistent over time (3

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Section: Discussionsupporting

confidence: 86%

Molecular Alterations in Spontaneous Sputum of Cancer-Free Heavy Smokers: Results from a Large Screening Program

Baryshnikova

Destro

Infante³

et al. 2008

Clinical Cancer Research

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“…We investigated RASSF1A hypermethylation as marker of tumour related DNA [28]. In our hands RASSF1A is more frequently present in sputum of lung cancer patients than in controls (data not shown).…”

Section: Dna Analysismentioning

confidence: 90%

Can free DNA be detected in sputum of lung cancer patients?

et al. 2008

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“…Several other means for early detection of lung cancer have been explored, including fluorescent bronchoscopy, endobronchial ultrasound-guided transbronchial needle aspiration, induced sputum analysis by different means and blood biomarkers [160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178]. Although bronchoscopic approaches have been found to be sensitive and specific tools for staging lung cancer, they are invasive techniques that limit their applicability for screening.…”

Section: Lung Cancer Screeningmentioning

confidence: 99%

Exhaled biomarkers in lung cancer

Horváth

Lázár

Gyulai

et al. 2009

European Respiratory Journal

239

206

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Lung cancer is the leading cause of cancer death. Results of therapeutic interventions are particularly discouraging when the disease is discovered in an advanced stage. Early diagnosis is limited by the fact that the disease usually develops asymptomatically and available screening methods do not fulfil the requirements for reliable discrimination between patients with lung cancer and subjects not suffering from the disease. Breath sampling is completely noninvasive and provides a potentially useful approach to screening lung cancer. Exhaled biomarkers contain both volatile and nonvolatile molecules. The profile of volatile organic compounds is different in patients with lung cancer than in control subjects. In exhaled breath condensate, the proteomic profile of breath from cancer patients differs from that of healthy smokers. We reviewed the scientific evidence demonstrating that a unique chemical signature can be detected in the breath of patients with lung cancer and that the exhaled breath biomarker profile could aid clinical decision making.KEYWORDS: Biomarker, electronic nose, exhaled breath, exhaled breath condensate, lung cancer, smell L ung cancer is the leading cause of global cancer death in both males and females. According to the most recent projection of global mortality, by 2030 it will emerge as the third and the fifth leading cause of death in highand middle-income countries, respectively [1,2]. Figures on disease outcome measures are very discouraging as even with the most advanced treatment strategies ,86% of lung cancer patients die within 5 yrs of diagnosis. With early detection and treatment, however, the 5-yr survival rate improves dramatically from 20% in patients with stage III lung cancer to 70% in patients with stage I disease [3]. Researchers, therefore, have sought out screening tests to detect lung cancer in the earliest stages and several promising new approaches have been proposed for this purpose, such as computer-assisted image analysis of chest radiographs, spiral computed tomography (CT) scanning, PCR-based assays of sputum and fluorescence bronchoscopy [4][5][6][7].Breath chemical tests have a broad spectrum of applications ranging from the US Food and Drug Administration-approved exhaled nitric oxide fraction (FeNO) measurement to monitor the effect of anti-inflammatory treatment in asthma, to volatile organic compound (VOC) determination and nonvolatile biomarker profiling in the cooled breath sample called exhaled breath condensate (EBC) [8][9][10][11]. Being completely noninvasive, sampling of the breath allows clinicians and researchers to assess different body functions in a flexible manner. Breath collection can be performed even in very severe patients and also repeated within short intervals. Therefore, breath testing is considered to be a potentially ideal candidate for screening purposes. Besides widely known constituents such as nitrogen, oxygen, carbon dioxide, inert gases and water vapour, exhaled breath also consists of thousands of volatile and nonv...

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Methylation profile in tumor and sputum samples of lung cancer patients detected by spiral computed tomography: A nested case–control study

Cited by 46 publications

References 23 publications

Molecular Alterations in Spontaneous Sputum of Cancer-Free Heavy Smokers: Results from a Large Screening Program

Molecular Alterations in Spontaneous Sputum of Cancer-Free Heavy Smokers: Results from a Large Screening Program

Can free DNA be detected in sputum of lung cancer patients?

Exhaled biomarkers in lung cancer

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