Skip to main content
Top
Published in: Cancer Cell International 1/2012

Open Access 01-12-2012 | Primary research

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

Authors: Yosuke Hanai, Ken Shimono, Hiroaki Oka, Yoshinobu Baba, Kunio Yamazaki, Gary K Beauchamp

Published in: Cancer Cell International | Issue 1/2012

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
2.
go back to reference Ludwig JA, Weinstein JN: Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005, 5: 845-856. 10.1038/nrc1739.CrossRefPubMed Ludwig JA, Weinstein JN: Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005, 5: 845-856. 10.1038/nrc1739.CrossRefPubMed
3.
go back to reference 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. 10.1056/NEJMoa0706550.CrossRefPubMed 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. 10.1056/NEJMoa0706550.CrossRefPubMed
4.
5.
go back to reference Greenberg AK, Lee MS: Biomarkers for lung cancer: clinical uses. Curr Opin Pulm Med. 2007, 13: 249-255. 10.1097/MCP.0b013e32819f8f06.CrossRefPubMed Greenberg AK, Lee MS: Biomarkers for lung cancer: clinical uses. Curr Opin Pulm Med. 2007, 13: 249-255. 10.1097/MCP.0b013e32819f8f06.CrossRefPubMed
6.
go back to reference Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Edited by: Amann A, Smith D. 2005, Singapore: World Scientific Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Edited by: Amann A, Smith D. 2005, Singapore: World Scientific
7.
go back to reference Amann A, Spanel P, Smith D: Breath analysis: the approach towards clinical applications. Mini-Rev Med Chem. 2007, 7: 115-129. 10.2174/138955707779802606.CrossRefPubMed Amann A, Spanel P, Smith D: Breath analysis: the approach towards clinical applications. Mini-Rev Med Chem. 2007, 7: 115-129. 10.2174/138955707779802606.CrossRefPubMed
8.
go back to reference Schubert J, Miekisch W, Noldge-Schomburg G: VOC breath markers in critically ill patients: potentials and limitations. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Edited by: Amann A, Smith D. 2005, Singapore: World Scientific, 267-292.CrossRef Schubert J, Miekisch W, Noldge-Schomburg G: VOC breath markers in critically ill patients: potentials and limitations. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. Edited by: Amann A, Smith D. 2005, Singapore: World Scientific, 267-292.CrossRef
9.
go back to reference Risby T, Amann A, Smith D: Current status of clinical breath analysis. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. 2005, Singapore: World Scientific, 251-265.CrossRef Risby T, Amann A, Smith D: Current status of clinical breath analysis. Breath Analysis for Clinical Diagnosis and Therapeutic Monitoring. 2005, Singapore: World Scientific, 251-265.CrossRef
10.
go back to reference 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. 10.1046/j.1440-1746.2003.02901.x.CrossRefPubMed 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. 10.1046/j.1440-1746.2003.02901.x.CrossRefPubMed
11.
go back to reference 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. 10.1046/j.1365-2036.2002.01212.x.CrossRefPubMed 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. 10.1046/j.1365-2036.2002.01212.x.CrossRefPubMed
12.
go back to reference Eisenmann A, Amann A, Said M, Datta B, Ledochowski M: Implementation and interpretation of hydrogen breath test. J Breath Res. 2008, 2 (4): 046002-10.1088/1752-7155/2/4/046002.CrossRefPubMed Eisenmann A, Amann A, Said M, Datta B, Ledochowski M: Implementation and interpretation of hydrogen breath test. J Breath Res. 2008, 2 (4): 046002-10.1088/1752-7155/2/4/046002.CrossRefPubMed
13.
14.
go back to reference 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.PubMed 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.PubMed
15.
go back to reference Simenhoff ML, Burke JF, Saukkonen JJ, Ordinario AT, Doty R: Biochemical profile or uremic breath. N Engl J Med. 1977, 297: 132-135. 10.1056/NEJM197707212970303.CrossRefPubMed Simenhoff ML, Burke JF, Saukkonen JJ, Ordinario AT, Doty R: Biochemical profile or uremic breath. N Engl J Med. 1977, 297: 132-135. 10.1056/NEJM197707212970303.CrossRefPubMed
16.
go back to reference Aghdassi E, Allard JP: Breath alkanes as a marker of oxidative stress in different clinical conditions. Free Radic Biol Med. 2000, 28: 880-886. 10.1016/S0891-5849(00)00189-1.CrossRefPubMed Aghdassi E, Allard JP: Breath alkanes as a marker of oxidative stress in different clinical conditions. Free Radic Biol Med. 2000, 28: 880-886. 10.1016/S0891-5849(00)00189-1.CrossRefPubMed
17.
go back to reference 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: 37-10.1186/1749-8090-2-37.PubMedCentralCrossRefPubMed 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: 37-10.1186/1749-8090-2-37.PubMedCentralCrossRefPubMed
18.
go back to reference 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.PubMed 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.PubMed
19.
go back to reference 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. 10.1378/chest.123.6.2115.CrossRefPubMed 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. 10.1378/chest.123.6.2115.CrossRefPubMed
20.
go back to reference 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. 10.1016/j.ijms.2007.05.012.CrossRef 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. 10.1016/j.ijms.2007.05.012.CrossRef
21.
go back to reference 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. 10.1164/rccm.200409-1184OC.PubMedCentralCrossRefPubMed 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. 10.1164/rccm.200409-1184OC.PubMedCentralCrossRefPubMed
22.
go back to reference 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. 10.1016/S0956-5663(03)00086-1.CrossRefPubMed 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. 10.1016/S0956-5663(03)00086-1.CrossRefPubMed
23.
go back to reference 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: 71-10.1186/1465-9921-6-71.PubMedCentralCrossRefPubMed 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: 71-10.1186/1465-9921-6-71.PubMedCentralCrossRefPubMed
24.
go back to reference 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. 10.1515/CCLM.2009.133.CrossRefPubMed 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. 10.1515/CCLM.2009.133.CrossRefPubMed
25.
go back to reference 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. 10.1002/cncr.22844.CrossRefPubMed 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. 10.1002/cncr.22844.CrossRefPubMed
26.
go back to reference 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. 10.1016/j.lungcan.2008.08.008.CrossRefPubMed 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. 10.1016/j.lungcan.2008.08.008.CrossRefPubMed
27.
go back to reference 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: 712-10.1136/bmj.329.7468.712.CrossRef 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: 712-10.1136/bmj.329.7468.712.CrossRef
28.
go back to reference 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. 10.1089/acm.2006.6408.CrossRef 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. 10.1089/acm.2006.6408.CrossRef
29.
go back to reference 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): e8819-10.1371/journal.pone.0008819.PubMedCentralCrossRefPubMed 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): e8819-10.1371/journal.pone.0008819.PubMedCentralCrossRefPubMed
30.
go back to reference 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. 10.1002/rcm.984.CrossRef 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. 10.1002/rcm.984.CrossRef
31.
go back to reference 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: 17-10.1186/1475-2867-8-17.CrossRef 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: 17-10.1186/1475-2867-8-17.CrossRef
32.
go back to reference 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.PubMed 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.PubMed
33.
go back to reference 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. 10.1021/ac051437y.CrossRefPubMed 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. 10.1021/ac051437y.CrossRefPubMed
34.
go back to reference 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. 10.1158/1055-9965.EPI-09-0162.CrossRef 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. 10.1158/1055-9965.EPI-09-0162.CrossRef
35.
go back to reference 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. 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.
go back to reference Kusuhara M, Urakami K, Zangicomi V, Hoshino K: Disease and smell: "Byoshu". Anti-Aging Med. 2010, 7 (6): 66-72. 10.3793/jaam.7.66.CrossRef Kusuhara M, Urakami K, Zangicomi V, Hoshino K: Disease and smell: "Byoshu". Anti-Aging Med. 2010, 7 (6): 66-72. 10.3793/jaam.7.66.CrossRef
Metadata
Title
Analysis of volatile organic compounds released from human lung cancer cells and from the urine of tumor-bearing mice
Authors
Yosuke Hanai
Ken Shimono
Hiroaki Oka
Yoshinobu Baba
Kunio Yamazaki
Gary K Beauchamp
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2012
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-12-7

Other articles of this Issue 1/2012

Cancer Cell International 1/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine