Early diagnosis of lung cancer based on proteome analysis of exhaled breath condensate

Fedorchenko, Kristina; Ryabokon, Anna; Kononikhin, Alexey; Mitrofanov, Sergey I.; Бармин, В. В.; Пикин, О. В.; Анаев, Э. Х.; Gachok, I. V.; Popov, Igor; Nikolaev, E. N.; Чучалин, А. Г.; Варфоломеев, С. Д.

doi:10.3103/s0027131416020036

Cited by 10 publications

(7 citation statements)

References 25 publications

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“…In agreement with other studies (14), we observed a high number of dermcidin peptides in the EBC of patients with lung cancer. This protein has also been found in the EBC samples of COPD, community-acquired pneumonia, and LC patients, although they did not observe differences between the groups (19). Dermcidin was originally identified as an antimicrobial peptide secreted by sweat glands (60).…”

Section: Discussionmentioning

confidence: 96%

“…A number of studies have reported the protein analysis in EBC ( 29), but only a few of them used a proteomic approach; most managed to identify a relatively small number of proteins (8,9,14,23,26,38,41). Only two recent studies have identified a larger number of proteins (19,49). Most studies to date analyzed pooled samples and are related to asthma or other lung diseases such as COPD, with only one study analyzing samples from patients with lung cancer using LC-MS/MS to map and quantify proteins identified (19).…”

Section: Discussionmentioning

confidence: 99%

“…Only two recent studies have identified a larger number of proteins (19,49). Most studies to date analyzed pooled samples and are related to asthma or other lung diseases such as COPD, with only one study analyzing samples from patients with lung cancer using LC-MS/MS to map and quantify proteins identified (19). This resulted in the identification of Ͼ300 proteins while 19 of them were found in EBC samples of the early stage lung cancer patients.…”

Section: Discussionmentioning

confidence: 99%

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Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics

López‐Sánchez

Jurado-Gámez

Feu-Collado

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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We explored whether the proteomic analysis of exhaled breath condensate (EBC) may provide biomarkers for noninvasive screening for the early detection of lung cancer (LC). EBC was collected from 192 individuals [49 control (C), 49 risk factor-smoking (S), 46 chronic obstructive pulmonary disease (COPD) and 48 LC]. With the use of liquid chromatography and tandem mass spectrometry, 348 different proteins with a different pattern among the four groups were identified in EBC samples. Significantly more proteins were identified in the EBC from LC compared with other groups (C: 12.4 ± 1.3; S: 15.3 ± 1; COPD: 14 ± 1.6; LC: 24.2 ± 3.6; = 0.0001). Furthermore, the average number of proteins identified per sample was significantly higher in LC patients, and receiver operating characteristic curve (ROC) analysis showed an area under the curve of 0.8, indicating diagnostic value. Proteins frequently detected in EBC, such as dermcidin and hornerin, along with others much less frequently detected, such as hemoglobin and histones, were identified. Cytokeratins (KRTs) were the most abundant proteins in EBC samples, and levels of KRT6A, KRT6B, and KRT6C isoforms were significantly higher in samples from LC patients ( = 0.0031, 0.0011, and 0.0009, respectively). Moreover, the amount of most KRTs in EBC samples from LC patients showed a significant positive correlation with tumor size. Finally, we used a random forest algorithm to generate a robust model using EBC protein data for the diagnosis of patients with LC where the area under the ROC curve obtained indicated a good classification (82%). Thus this study demonstrates that the proteomic analysis of EBC samples is an appropriated approach to develop biomarkers for the diagnosis of lung cancer.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics

López‐Sánchez

Jurado-Gámez

Feu-Collado

et al. 2017

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In previous studies cytoskeleton keratins were shown as to be main proteins in the EBC of healthy peoples [44,45]. Some of them are also associated with different pathologies of the respiratory system such as pneumonia and lung cancer [37,38,46]. Due to Protein Atlas, keratins KRT1 , KRT 2 , KRT 9 , and KRT 10 have epidermal origin and can contaminate samples during sample preparation.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, 8-isoprostane is considered to be a biomarker of oxidative stress [32] and the pH of EBC can be considered as a simple but reliable biomarker of various lung diseases [33,34,35]. A number of proteins including cytokeratins (1, 5, 9, and 14), C-reactive protein, interleukins (IL-1α, IL-1β, IL-2, IL-12α, IL-12β, and IL-15), tumor necrosis factor-α, C3 complement component, and interferons α and γ, as well as proteome profiles have been shown to be characteristic for particular pathologies, including asthma, chronic obstructive pulmonary disease, lung cancer, and so on [36,37,38]. However, most useful for the present study is the fact that EBC composition reflects the real-time state of the respiratory system.…”

Section: Introductionmentioning

confidence: 99%

Proteome Profiling of the Exhaled Breath Condensate after Long-Term Spaceflights

Kononikhin

Brzhozovskiy

Ryabokon

et al. 2019

IJMS

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Comprehensive studies of the effects of prolonged exposure to space conditions and the overload experienced during landing on physiological and biochemical changes in the human body are extremely important in the context of planning long-distance space flights, which can be associated with constant overloads and various risk factors for significant physiological changes. Exhaled breath condensate (EBC) can be considered as a valuable subject for monitoring physiological changes and is more suitable for long-term storage than traditional monitoring subjects such as blood and urine. Herein, the EBC proteome changes due to the effects of spaceflight factors are analyzed. Thirteen EBC samples were collected from five Russian cosmonauts (i) one month before flight (background), (ii) immediately upon landing modules in the field (R0) after 169–199 days spaceflights, and (iii) on the seventh day after landing (R+7). Semi-quantitative label-free EBC proteomic analysis resulted in 164 proteins, the highest number of which was detected in EBC after landing (R0). Pathways enrichment analysis using the GO database reveals a large group of proteins which take part in keratinization processes (CASP14, DSG1, DSP, JUP, and so on). Nine proteins (including KRT2, KRT9, KRT1, KRT10, KRT14, DCD, KRT6C, KRT6A, and KRT5) were detected in all three groups. A two-sample Welch’s t-test identified a significant change in KRT2 and KRT9 levels after landing. Enrichment analysis using the KEGG database revealed the significant participation of detected proteins in pathogenic E. coli infection (ACTG1, TUBA1C, TUBA4A, TUBB, TUBB8, and YWHAZ), which may indicate microbiota changes associated with being in space. This assumption is confirmed by microbial composition analysis. In general, the results suggest that EBC can be used for noninvasive monitoring of health status and respiratory tract pathologies during spaceflights, and that the obtained data are important for the development of medicine for use in extreme situations. Data are available from ProteomeXchange using the identifier PXD014191.

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The effect of space flight on the protein composition of the exhaled breath condensate of cosmonauts

et al. 2016

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Early diagnosis of lung cancer based on proteome analysis of exhaled breath condensate

Cited by 10 publications

References 25 publications

Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics

Exhaled breath condensate biomarkers for the early diagnosis of lung cancer using proteomics

Proteome Profiling of the Exhaled Breath Condensate after Long-Term Spaceflights

The effect of space flight on the protein composition of the exhaled breath condensate of cosmonauts

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