Panel of serum metabolites discriminates cancer patients and healthy participants of lung cancer screening - a pilot study

• Authors: Małgorzata Roś-Mazurczyk , Anna Wojakowska , Łukasz Marczak , Krzysztof Polański , Monika Pietrowska , Joanna Polanska , Rafał Dziadziuszko , Jacek Jassem , Witold Rzyman , Piotr Widlak
• Languages of publication: EN

Abstracts

EN

Introduction. Blood biomarkers may support early diagnosis of lung cancer by enabling pre-selection of candidates for computed tomography screening or discrimination between benign and malignant screening-detected nodules. We aimed to identify features of serum metabolome distinguishing individuals with early-detected lung cancer from healthy participants of the lung cancer screening program. Methods. Blood samples were collected in the course of a low-dose computed tomography screening program performed in the Gdansk district (Northern Poland). The analysis included 31 patients with screening-detected lung cancer and the pair-matched group of 92 healthy controls. The gas chromatography coupled to mass spectrometry (GC/MS) approach was used to identify and quantify small metabolites present in serum. Results. There were several metabolites detected in the sera whose abundances discriminated patients with lung cancer from controls. Majority of the differentiating components were downregulated in cancer samples, including amino acids, carboxylic acids and tocopherols, whereas benzaldehyde was the only compound significantly upregulated. A classifier including nine serum metabolites allowed separation of cancer and control samples with 100% sensitivity and 95% specificity. Conclusions. Signature of serum metabolites discriminating between cancer patients and healthy participants of the early lung cancer screening program was identified using a GC/MS metabolomics approach. This signature, though not validated in an independent dataset, deserves further investigation in a larger cohort study.

Keywords

EN

early detection; lung cancer screening; metabolomics; serum biomarkers

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2017
• Volume: 64
• Issue: 3
• Pages: 513-518

Dates

published

2017

received

2017-01-31

revised

2017-06-27

accepted

2017-07-17

(unknown)

2017-08-12

Contributors

author

Małgorzata Roś-Mazurczyk

• Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

author

Anna Wojakowska

• Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

author

Łukasz Marczak

• Polish Academy of Science, Institute of Bioorganic Chemistry, Poznań, Poland

author

Krzysztof Polański

• University of Warvick, Coventry, Great Britain

author

Monika Pietrowska

• Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

author

Joanna Polanska

• Silesian University of Technology, Gliwice, Poland

author

Rafał Dziadziuszko

• Medical University of Gdańsk, Gdańsk, Poland

author

Jacek Jassem

• Medical University of Gdańsk, Gdańsk, Poland

author

Witold Rzyman

• Medical University of Gdańsk, Gdańsk, Poland

author

Piotr Widlak

• Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland

References

• Aberle DR, Adams AM, Berg CD, et al. (2011) National lung screening trial research team reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365: 395-409. http:// doi: 10.1056/NEJMoa1102873.
• Bajtarevic A, Ager C, Pienz M, Klieber M, Schwarz K, Ligor M, Ligor T, Filipiak W, Denz H, Fiegl M, Hilbe W, Weiss W, Lukas P, Jamnig H, Hackl M, Haidenberger A, Buszewski B, Miekisch W, Schubert J, Amann A (2009) Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9: 348. http:// doi: 10.1186/1471-2407-9-348.
• Chen Y, Ma Z, Min L, Li H, Wang B, Zhong J, Dai L (2015) Biomarker identification and pathway analysis by serum metabolomics of lung cancer. Biomed Res Int 2015: 183624. http:// doi: 10.1155/2015/183624.
• Comstock GW, Alberg AJ, Huang HY, Wu K, Burke AE, Hoffman SC, Norkus EP, Gross M, Cutler RG, Morris JS, Spate VL, Helzlsouer KJ (2008) The risk of developing lung cancer associated with antioxidants in the blood: ascorbic acids, carotenoids, alpha-tocopherol, selenium, and total peroxyl radical absorbing capacity. Am J Epidemiol 168: 831-840. http:// doi: 10.1093/aje/kwn328.
• Deja S, Porebska I, Kowal A, Zabek A, Barg W, Pawelczyk K, Stanimirova I, Daszykowski M, Korzeniewska A, Jankowska R, Mlynarz P (2014) Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease. J Pharm Biomed Anal 100: 369-380. http:// doi: 10.1016/j.jpba.2014.08.020.
• Guo Y, Wang X, Qiu L, Qin X, Liu H, Wang Y, Li F, Wang X, Chen G, Song G, Li F, Guo S, Li Z (2012) Probing gender-specific lipid metabolites and diagnostic biomarkers for lung cancer using Fourier transform ion cyclotron resonance mass spectrometry. Clin Chim Acta 414: 135-141. http:// doi: 10.1016/j.cca.2012.08.010.
• Hassanein M, Callison JC, Callaway-Lane C, Aldrich MC, Grogan EL, Massion PP (2012) The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res (Phila) 5: 992-1006. http:// doi: 10.1158/1940-6207.CAPR-11-0441.
• Hassanein M, Rahman JS, Chaurand P, Massion PP (2011) Advances in proteomic strategies toward the early detection of lung cancer. Proc Am Thorac Soc 8: 183-188. http:// doi: 10.1513/pats.201012-069MS.
• Hoffman PC, Mauer AM, Vokes EE (2000) Lung cancer. Lancet 355: 479-485. http:// doi: 10.1016/S0140-6736(00)82038-3.
• Hori S, Nishiumi S, Kobayashi K, Shinohara M , Hatakeyama Y, Kotani Y, Hatano N, Maniwa Y, Nishio W, Bamba T, Fukusaki E, Azuma T, Takenawa T, Nishimura Y, Yoshida M (2011) A metabolomic approach to lung cancer. Lung Cancer 74: 284-292. http:// doi: 10.1016/j.lungcan.2011.02.008.
• Jemal A, Center MM, DeSantis C, Ward EM (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev 19: 1893-1907. http:// doi: 10.1158/1055-9965.EPI-10-0437.
• Jordan KW, Adkins CB, Su L, Halpern EF, Mark EJ, Christiani DC, Cheng LL (2010) Comparison of squamous cell carcinoma and adenocarcinoma of the lung by metabolomic analysis of tissue-serum pairs, Lung Cancer 68: 44-50. http:// doi: 10.1016/j.lungcan.2009.05.012.
• Liu J, Mazzone PJ, Cata JP, Kurz A, Bauer M, Mascha EJ, Sessler DI (2014) Serum free fatty acid biomarkers of lung cancer. Chest 146: 670-679. http:// doi: 10.1378/chest.13-2568.
• Louis E, Adriaensens P, Guedens W, Bigirumurame T, Baeten K, Vanhove K, Vandeurzen K, Darquennes K, Vansteenkiste J, Dooms C, Shkedy Z, Mesotten L, Thomeer M (2016) Detection of lung cancer through metabolic changes measured in blood plasma. J Thorac Oncol 11: 516-523. http:// doi: 10.1016/j.jtho.2016.01.011.
• Mahabir S, Schendel K, Dong YQ, Barrera SL, Spitz MR, Forman MR (2008) Dietary alpha-, beta-, gamma- and delta-tocopherols in lung cancer risk. Int J Cancer 123: 1173-1180. http:// doi: 10.1002/ijc.23649.
• Mazzone PJ, Wang XF, Beukemann M, Zhang Q, Seeley M, Mohney R, Holt T, Pappan KL (2016) Metabolite profiles of the serum of patients with non-small cell carcinoma. J Thorac Oncol 11: 72-88. http:// doi: 10.1016/j.jtho.2015.09.002.
• Priola AM, Priola SM, Giaj-Levra M, Basso E, Veltri A, Fava C, Cardinale L. (2013) Clinical implications and added costs of incidental findings in an early detection study of lung cancer by using low-dose spiral computed tomography. Clin Lung Cancer 14: 139-148. http:// doi: 10.1016/j.cllc.2012.05.005.
• Puchades-Carrasco L, Jantus-Lewintre E, Pérez-Rambla C, García-García F, Lucas R, Calabuig S, Blasco A, Dopazo J, Camps C, Pineda-Lucena A (2016) Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer. Oncotarget 7: 12904-12916. http:// doi: 10.18632/oncotarget.7354.
• Rocha CM, Carrola J, Barros AS, Gil AM, Goodfellow BJ, Carreira IM, Bernardo J, Gomes A, Sousa V, Carvalho L, Duarte IF (2011) Metabolic signatures of lung cancer in biofluids: NMR-based metabonomics of blood plasma. J Proteome Res 10: 4314-4324. http:// doi: 10.1021/pr200550p.
• Rzyman W, Dziedzic R, Jelitto-Górska M, Biadacz I, Książek J, Siebert J, Zdrojewski T, Studniarek M (2015) Results of an open-access lung cancer screening program with low-dose computed tomography: the Gdańsk experience. Pol Arch Med Wewn 125: 232-239.
• Rzyman W, Jelitto-Gorska M, Dziedzic R, Biadacz I, Ksiazek J, Chwirot P, Marjanski T (2013) Diagnostic work-up and surgery in participants of the Gdansk lung cancer screening programme: the incidence of surgery for non-malignant conditions. Interact Cardiovasc Thorac Surg 17: 969-973. http:// doi: 10.1093/icvts/ivt388.
• Sozzi G, Boeri M (2014) Potential biomarkers for lung cancer screening. Transl Lung Cancer Res 3: 139-1348. http:// doi: 10.3978/j.issn.2218-6751.2014.06.04.
• Spratlin JL, Serkova NJ, Eckhardt SG (2009) Clinical applications of metabolomics in oncology: a review. Clin Cancer Res 15: 431-440. http:// doi: 10.1158/1078-0432.CCR-08-1059.
• Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65: 87-108. http:// doi: 10.3322/caac.21262.
• Virtamo J, Taylor PR, Kontto J, Männistö S, Utriainen M, Weinstein SJ, Huttunen J, Albanes D (2014) Effects of α-tocopherol and β-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the Alpha-tocopherol, Beta-carotene Cancer Prevention Study. Int J Cancer 135: 178-185. http:// doi: 10.1002/ijc.28641.
• Wang L, Tang Y, Liu S, Mao S, Ling Y, Liu D, He X, Wang X (2013) Metabonomic profiling of serum and urine by (1)H NMR-based spectroscopy discriminates patients with chronic obstructive pulmonary disease and healthy individuals. PloS One 8: e65675. http:// doi: 10.1371/journal.pone.0065675.
• Willett WC, Polk BF, Underwood BA, Stampfer MJ, Pressel S, Rosner B, Taylor JO, Schneider K, Hames CG. (1984) Relation of serum vitamins A and E and carotenoids to the risk of cancer. N Engl J Med 310: 430-434.
• Wright GS, Gruidl ME (2000) Early detection and prevention of lung cancer. Curr Opin Oncol 12: 143-148.
• Wu QJ, Xiang YB, Yang G, Li HL, Lan Q, Gao YT, Zheng W, Shu XO, Fowke JH (2015) Vitamin E intake and the lung cancer risk among female nonsmokers: a report from the Shanghai Women's Health Study. Int J Cancer 136: 610-617. http:// doi: 10.1002/ijc.29016.

Identifiers

DOI

10.18388/abp.2017_1517