Analysis of volatile organic compounds released from human lung cancer cells and from the urine of tumor-bearing mice

Cancer Cell International

Gary K Beauchamp⁴  Kunio Yamazaki⁴  Yoshinobu Baba²  Hiroaki Oka¹  Ken Shimono¹  Yosuke Hanai³ 

[1] Bioscience Technology Development Office, Panasonic Corporation, Kyoto 619-0237, Japan;Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan;FRIST Research Center for Innovative Nanobiodevice, Nagoya University, Nagoya 464-8603, Japan;Monell Chemical Senses Center, Philadelphia, PA 19104-3308, USA

关键词: Tumor-bearing mice;    Urine;    Cell medium;    GC-TOF MS;    VOCs;    Lung cancer;   

Others  :  795227
DOI  :  10.1186/1475-2867-12-7

 received in 2011-09-07, accepted in 2012-02-24,  发布年份 2012

【 摘 要 】

Backgrounds

A potential strategy for the diagnosis of lung cancer is to exploit the distinct metabolic signature of this disease by way of biomarkers found in different sample types. In this study, we investigated whether specific volatile organic compounds (VOCs) could be detected in the culture medium of the lung cancer cell line A549 in addition to the urine of mice implanted with A549 cells.

Results

Several VOCs were found at significantly increased or decreased concentrations in the headspace of the A549 cell culture medium as compared with the culture medium of two normal lung cell lines. We also analyzed the urine of mice implanted with A549 cells and several VOCs were also found to be significantly increased or decreased relative to urine obtained from control mice. It was also revealed that seven VOCs were found at increased concentrations in both sample types. These compounds were found to be dimethyl succinate, 2-pentanone, phenol, 2-methylpyrazine, 2-hexanone, 2-butanone and acetophenone.

Conclusions

Both sample types produce distinct biomarker profiles, and VOCs have potential to distinguish between true- and false-positive screens for lung cancer.

【 授权许可】

   
2012 Hanai et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 3.

【 参考文献 】

• [1]World Health Organization. Cancer, Factsheet N 297 [http://www.who.int/mediacentre/factsheets/fs297/en/] webcite Last updated February 2011
• [2]Ludwig JA, Weinstein JN: Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005, 5:845-856.
• [3]Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glöckner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG: DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 2008, 358:1118-1128.
• [4]Sawyers CL: The cancer biomarker problem. Nature 2008, 452:548-552.
• [5]Greenberg AK, Lee MS: Biomarkers for lung cancer: clinical uses. Curr Opin Pulm Med 2007, 13:249-255.
• [6]Amann A, Smith D (Eds): Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Singapore: World Scientific; 2005.
• [7]Amann A, Spanel P, Smith D: Breath analysis: the approach towards clinical applications. Mini-Rev Med Chem 2007, 7:115-129.
• [8]Schubert J, Miekisch W, Noldge-Schomburg G: VOC breath markers in critically ill patients: potentials and limitations. In Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Edited by Amann A, Smith D. Singapore: World Scientific; 2005:267-292.
• [9]Risby T, Amann A, Smith D: Current status of clinical breath analysis. In Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Singapore: World Scientific; 2005:251-265.
• [10]Chen CP, Chen CY, Lu CL, Chang FY, Lee SD, Chu LS, Liu RS, Wu HC: Infrared spectrometry based 13 C-octanoic acid breath test in measuring human solid gastric emptying. J Gastroenterol Hepatol 2003, 18:41-46.
• [11]Liao CC, Lee CL, Chiang TC, Lee SC, Huang SH, Tu TC, Chen TK, Wu CH: The 13 C-urea breath test to detect Helicobacter pylori infection: a validated simple methodology with 50 mg 13C-urea. Aliment Pharmacol Ther 2002, 16:787-792.
• [12]Eisenmann A, Amann A, Said M, Datta B, Ledochowski M: Implementation and interpretation of hydrogen breath test. J Breath Res 2008, 2(4):046002.
• [13]Lebovitz HE: Diabetic ketoacidosis. Lancet 1995, 345:767-772.
• [14]Chen S, Zieve L, Mahadevan V: Mercaptans and dimethyl sulfide in the breath of patients with cirrhosis of the liver. Effect of feeding methionine. J Lab Clin Med 1970, 75:628-635.
• [15]Simenhoff ML, Burke JF, Saukkonen JJ, Ordinario AT, Doty R: Biochemical profile or uremic breath. N Engl J Med 1977, 297:132-135.
• [16]Aghdassi E, Allard JP: Breath alkanes as a marker of oxidative stress in different clinical conditions. Free Radic Biol Med 2000, 28:880-886.
• [17]Pabst F, Miekisch W, Fuchs P, Kischkel S, Schubert JK: Monitoring of oxidative and metabolic stress during cardiac surgery by means of breath biomarkers: an observational study. J Cardiothorac Surg 2007, 2:37. BioMed Central Full Text
• [18]Phillips M, Altorki N, Austin JH, Cameron RB, Cataneo RN, Greenberg J, Kloss R, Maxfield RA, Munawar MI, Pass HI, Rashid A, Rom WN, Schmitt P: Prediction of lung cancer using volatile biomarkers in breath. Cancer Biomarkers 2007, 3:95-109.
• [19]Phillips M, Cataneo RN, Cummin AR, Gagliardi AJ, Gleeson K, Greenberg J, Maxfield RA, Rom WN: Detection of lung cancer with volatile markers in the breath. Chest 2003, 123:2115-2123.
• [20]Wehinger A, Schmid A, Mechtcheriakov S, Ledochowski M, Grabmer C, Gastl GA, Amann A: Lung cancer detection by proton transfer reaction mass spectrometric analysis of human breath gas. Int J Mass Spectrom 2007, 265:49-59.
• [21]Machado RF, Laskowski D, Deffenderfer O, Burch T, Zheng S, Mazzone PJ, Mekhail T, Jennings C, Stoller JK, Pyle J, Duncan J, Dweik RA, Erzurum SC: Detection of lung cancer by sensor array analyses of exhaled breath. Am J Respir Crit Care Med 2005, 171:1286-1291.
• [22]Di Natale C, Macagnano A, Martinelli E, Paolesse R, D'Arcangelo G, Roscioni C, Finazzi-Agrò A, D'Amico A: Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensors. Biosens Bioelectron 2003, 18:1209-1218.
• [23]Poli D, Carbognani P, Corradi M, Goldoni M, Acampa O, Balbi B, Bianchi L, Rusca M, Mutti A: Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study. Respir Res 2005, 6:71. BioMed Central Full Text
• [24]Ligor M, Ligor T, Bajtarevic A, Ager C, Pienz M, Klieber M, Denz H, Fiegl M, Hilbe W, Weiss W, Lukas P, Jamnig H, Hackl M, Buszewski B, Miekisch W, Schubert J, Amann A: Determination of volatile organic compounds appearing in exhaled breath of lung cancer patients by solid phase microextraction and gas chromatography mass spectrometry. Clin Chem Lab Med 2009, 47:550-560.
• [25]Chen X, Xu F, Wang Y, Pan Y, Lu D, Wang P, Ying K, Chen E, Zhang W: A study of the volatile organic compounds exhaled by lung cancer cells in Vitro for breath diagnosis. Cancer 2007, 110:835-844.
• [26]Dragonieri S, Annema JT, Schot R, van der Schee MP, Spanevello A, Carratú P, Resta O, Rabe KF, Sterk PJ: An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD. Lung Cancer 2009, 64:166-170.
• [27]Willis CM, Church SM, Guest CM, Cook WA, McCarthy N, Bransbury AJ, Church MR, Church JC: Olfactory detection of human bladder cancer by dogs: proof of principle study. British Med J 2004, 329:712.
• [28]Gordon RT, Schatz CB, Myers LJ, Kosty M, Gonczy C, Kroener J, Tran M, Kurtzhals P, Heath S, Koziol JA, Arthur N, Gabriel M, Hemping J, Hemping G, Nesbitt S, Tucker-Clark L, Zaayer J: The use of canines in the detection of human cancers. J Alter Compl Med 2008, 14:61-67.
• [29]Matsumura K, Opiekun M, Oka H, Vachani A, Albelda SM, Yamazaki K, Beauchamp GK: Urinary volatile compounds as biomarkers for lung cancer: a proof of principle study using odor signatures in mouse models of lung cancer. PLoS One 2010, 5(1):e8819.
• [30]Smith D, Wang TS, Sule-Suso J, Spanel P, El Haj A: Quantification of acetaldehyde released by lung cancer cells in vitro using selected ion flow tube mass spectrometry. Rapid Comm Mass Spectrom 2003, 17:845-850.
• [31]Filipiak W, Sponring A, Mikoviny T, Ager C, Schubert J, Miekisch W, Amann A, Troppmair J: Release of volatile organic compounds (VOCs) from the lung cancer cell line CALU-1 in vitro. Canc Cell Intl 2008, 8:17. BioMed Central Full Text
• [32]Sponring A, Filipiak W, Mikoviny T, Ager C, Schubert J, Miekisch W, Amann A, Troppmair J: Release of volatile organic compounds from the lung cancer cell line NCI-H2087 in vitro. Anticancer Res 2009, 29:419-426.
• [33]Smith CA, Want EJ, O'Maille G, Abagyan R, Sizudak G: XCMS: Processing Mass Spectrometry Data for Metabolite Profiling Using Nonlinear Peak Alignment, Matching, and Identification. Anal Chem 2006, 78:779-787.
• [34]Filipiak W, Sponring A, Filipiak A, Ager C, Schubert J, Miekisch W, Amann A, Troppmair J: TD-GC-MS Analysis of Volatile Metabolites of Human Lung Cancer and Normal Cells In vitro. Canc Epidemiol Biomarkers Prev 2010, 19:182-195.
• [35]O'Nell HJ, Gordon SM, O'Nell MH, Glbbons RD, Szldon JP: A computerized classification technique for screening for the presence of breath biomarkers in lung cancer. Clin Chem 1988, 34/8:1613-1618.
• [36]Kusuhara M, Urakami K, Zangicomi V, Hoshino K: Disease and smell: "Byoshu". Anti-Aging Med 2010, 7(6):66-72.