Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate Detected by<sup>1</sup>H Magnetic Resonance Spectroscopy: A Feasibility Study

Ahmed, Naseer; Bezabeh, Tedros; Ijare, Omkar B.; Myers, Renelle; Alomran, Reem; Aliani, Michel; Nugent, Zoann; Banerji, Shantanu; Kim, Julian; Qing, Gefei; Bshouty, Zoheir

doi:10.4137/mri.s40864

Cited by 17 publications

(21 citation statements)

References 36 publications

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“…Our team has recently completed and published a feasibility study on bio-fluids obtained from advanced stage lung cancer patients using MRS. We have demonstrated absence of glucose in the sputum and decreased concentration of methanol in breath condensate of pathologically proven NSCLC in comparison to patients without lung cancer [15].…”

Section: Scientific Rationalementioning

confidence: 99%

Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

Ahmed

Kidane

Wang

et al. 2019

Contemporary Clinical Trials Communications

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BackgroundLung cancer is a major cause of global morbidity and mortality. Current low dose CT screening is invasive and its role remains contentious. There are no known biomarkers to monitor treatment response, detect disease recurrence and patient selection for adjuvant treatment after curative surgical resection. Hence there is an urgent need to explore non-conventional and non-invasive tools to develop novel biomarkers to improve the outcome of this lethal cancer.MethodsThis is an ongoing exploratory and translational study involving collection of bio fluids from 50 patients with early stage non-small cell lung cancer before and after surgical resection. The primary objective is to identify cancer specific metabolome in body fluids - sputum, exhaled breath condensate, blood and urine of the patients with early stage non-small cell lung cancer using Magnetic Resonance Spectroscopy and Mass Spectroscopy.ConclusionThe trajectory of change in metabolic profile of body fluids before and after surgical resection may have potential clinical applications in lung cancer screening, as biomarkers for disease recurrence and exploration of novel targets for therapeutic intervention.

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Section: Scientific Rationalementioning

confidence: 99%

Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

Ahmed

Kidane

Wang

et al. 2019

Contemporary Clinical Trials Communications

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“…Biofluids (sputum, blood, urine) have also been considered to help identify subjects who should undergo LDCT. 4,5 …”

Section: Introductionmentioning

confidence: 99%

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Barón

Kako

Feser

et al. 2017

Journal of Thoracic Oncology

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Introduction Low dose CT screening for lung cancer has a high false positive rate with frequent discovery of indeterminate pulmonary nodules. Noninvasive biomarkers are needed to reduce false positives and improve risk stratification. A retrospective longitudinal evaluation was performed to assess chromosomal aneusomy in sputum via fluorescence in situ hybridization (CA-FISH) in four nested case-control studies. Methods ROC analysis resulted in two grouped cohorts: High Risk (CO High Risk and CO Nodule; 68 Cases, 69 controls) and Screening (ACRIN/NLST and PLuSS; 97 Cases, 185 controls). The CA-FISH assay was a 4-target DNA panel encompassing EGFR and MYC genes, and the 5p15 and centromere 6 regions or the FGFR1 and PIK3CA genes. A 4-category scale: normal, probably normal, probably abnormal and abnormal was applied. Sensitivity, specificity, and positive and negative likelihood ratios (LR+, LR−) (with 95% CI) were estimated for each cohort. Results Sensitivity and specificity were, respectively, 0.67 (0.55, 0.78) and 0.94 (0.85, 0.98) for High Risk subjects and 0.20 (0.13, 0.30) and 0.84 (0.78, 0.89) for Screening subjects. LR+ and LR− were, respectively, 11.66 (4.44, 30.63) and 0.34 (0.24, 0.48) for High Risk; and 1.36 (0.81, 2.28) and 0.93 (0.83, 1.05) for Screening subjects. Conclusion The high positive likelihood ratio of sputum CA-FISH indicates it could be a useful adjunct to LDCT for lung cancer in high risk settings. For screening, however, its low positive likelihood ratio limits clinical utility. Prospective assessment of CA-FISH in the incidentally-identified indeterminate nodule setting is ongoing in the Colorado Pulmonary Nodule Biomarker Trial.

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“…Asthma, instead, presents a weaker risk of lung cancer in nonsmokers, and shows high levels of formate. This may be related to the in vitro antiproliferative effect on lung cancer cell lines of formate [13], which, on the contrary, decreases in the sputum of lung cancer patients [14].…”

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Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study

et al. 2018

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Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with high pathological burden and healthcare costs [1-3]. In outpatient clinical practice, an accurate differential diagnosis is often very difficult, particularly in adult smokers, requiring specific lung function tests [4, 5]. Since nuclear magnetic resonance (NMR)-based metabolomics of exhaled breath condensate (EBC) discriminates adults with COPD [6-8] or asthma [9] from healthy subjects, we hypothesised that it is also able to differentiate asthma and COPD patients of different severities. After approval by the Maugeri ethics committee, we recruited prospectively patients with a new diagnosis of asthma (n=31) and COPD (n=44) according to current Global Initiative for Asthma and Global Initiative for Chronic Obstructive Lung Disease guidelines. Six patients with asthma and nine COPD patients were excluded because of relevant comorbidities that could potentially affect the analysis (nine for the presence of coronary or valvular heart disease, five for the presence of diabetes mellitus, one for hypothyroidism). In addition, the EBC samples obtained from five asthma and three COPD subjects were technically unsuitable for NMR analysis. The final 20 asthma and 32 COPD subjects were used to build the reference statistical model (table 1). Since no a priori analysis was possible, we could only evaluate the adequacy of our sample size a posteriori, estimating a sample size of 17±3 asthma and 23±3 COPD patients. A second cohort was also enrolled for an external blind validation comprising 13 asthma and 20 COPD patients. EBC collection was achieved with a TURBO-DECCS condenser (Medivac, Pilastrello, Italy) as reported [10]. NMR spectra were recorded at 27°C in a randomised sequential order on a 600-MHz Bruker Avance-III spectrometer (Bruker BioSpin GmbH, Rheinstetten, Germany) equipped with a CryoProbe using standard experiments. Metabolites were identified by resorting to two-dimensional experiments. Within-day, between-day, and technical repeatability, and detection limit were assessed as reported [7, 9]. Proton NMR spectra were automatically data reduced to 390 integral segments ("buckets"), each of 0.02 ppm, using the Bruker AMIX 3.6 software package. Unsupervised principal component analysis (PCA) was first applied. However, to better identify clustering, we used orthogonal projections to latent structures discriminant analysis (OPLS-DA), and the obtained model showed improved predictive and interpretive abilities, and in a permutation test (n=300) revealed no overfit. The model quality was evaluated via the goodness-of-fit (R 2) and the goodness-of-prediction (Q 2) parameters [11]. Metabolite quantification was obtained using the corresponding normalised buckets. Metabolite statistical significance was determined by parametric (t-test) or non-parametric (Mann−Whitney U-test) tests according to the results of a normality test performed to evaluate each distribution (Shapiro−Wilk, Kolgomorov−Smirnov test). p-values <0.05 were conside...

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Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate Detected by¹H Magnetic Resonance Spectroscopy: A Feasibility Study

Cited by 17 publications

References 36 publications

Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study

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Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate Detected by1H Magnetic Resonance Spectroscopy: A Feasibility Study

Cited by 17 publications

References 36 publications

Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

Non-invasive exploration of metabolic profile of lung cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer

Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study

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Metabolic Signatures of Lung Cancer in Sputum and Exhaled Breath Condensate Detected by¹H Magnetic Resonance Spectroscopy: A Feasibility Study