Proton Magnetic Resonance Spectroscopy of Sputum for the Non-Invasive Diagnosis of Lung Cancer: Preliminary Findings

Authors

  • Tedros Bezabeh National Research Council, Institute for Biodiagnostics, Winnipeg, Manitoba, Canada
  • Omkar B. Ijare National Research Council, Institute for Biodiagnostics, Winnipeg, Manitoba, Canada
  • E. Celia Marginean Ottawa Hospital, Ottawa, Ontario, Canada
  • Garth Nicholas Ottawa Hospital, Ottawa, Ontario, Canada

DOI:

https://doi.org/10.6000/1927-7229.2012.01.01.3

Keywords:

Cytology, glucose, lung cancer, magnetic resonance spectroscopy, sputum analysis

Abstract

 Aims and Background: Sputum has been examined for the identification of potential biomarkers for the non-invasive diagnosis of lung cancer. However, no definitive biomarkers with reliable accuracy have been identified yet. The main objective of this work was to evaluate the utility of magnetic resonance spectroscopy (MRS) in the analysis of sputum for the non-invasive diagnosis of lung cancer. Methods: Induced sputum samples from lung cancer patients (n = 9) and control subjects (n = 6) were collected for proton (1H) MRS analysis. Samples from two cancer patients and one control subject were discarded as these samples were confirmed to contain only saliva by cytologic examination. Only the true sputum specimens containing alveolar macrophages were analyzed by 1H MRS. To facilitate MRS analysis, sputum samples were dispersed in 2M sodium chloride solution buffered with phosphate-buffered-saline (PBS). MR spectra were obtained using a one-pulse sequence with presaturation of the water resonance. Results: Glucose was found to be absent in sputum samples obtained from lung cancer patients. Spectra of sputum samples collected from control subjects showed presence of glucose signal except for one whose sputum cytology indicated the presence of atypia. The absence of glucose in sputum from cancer patients could be attributed to an increased rate of glycolysis in the lung cancer cells. The present observation, albeit on a small sample size, showed a better sensitivity (100%) and overall accuracy (92%) compared to sputum cytology (sensitivity = 50%; overall accuracy = 70%). Conclusions: Absence of glucose in sputum could be an indicator of lung cancer and the present methodology can be a valuable addition to the non-invasive diagnostics of lung cancer.

References

National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365: 395-409. http://dx.doi.org/10.1056/NEJMoa1102873

Lung cancer-National cancer institute: 2012, Available from: http://www.cancer.gov/cancertopics/types/lung

Mascaux C, Peled N, Garg K, Kato Y, Wynes MW, Hirsch FR. Early detection and screening of lung cancer. Expert Rev Mol Diagn 2010; 10: 799-15. http://dx.doi.org/10.1586/erm.10.60

Collins LG, Haines C, Perkel R, Enck RE. Lung cancer: diagnosis and management. Am Fam Physician 2007; 75: 56-63.

Prindiville SA, Ried T. Interphase cytogenetics of sputum cells for the early detection of lung carcinogenesis. Cancer Prev Res (Phila Pa) 2010; 3: 416-19. http://dx.doi.org/10.1158/1940-6207.CAPR-10-0045

Gomperts BN, Spira A, Elashoff DE, Dubinett SM. Lung cancer biomarkers: FISHing in the sputum for risk assessment and early detection. Cancer Prev Res 2010; 3: 420-23. http://dx.doi.org/10.1158/1940-6207.CAPR-10-0052

Bertram HC, Eggers N, Eller N. Potential of human saliva for nuclear magnetic resonance-based metabolomics and for health-related biomarker identification. Anal Chem 2009; 81: 9188-93. http://dx.doi.org/10.1021/ac9020598

Saude EJ, Lacy P, Musat-Marcu S, et al. NMR analysis of neutrophil activation in sputum samples from patients with cystic fibrosis. Magn Reson Med 2004; 52: 807-14. http://dx.doi.org/10.1002/mrm.20242

Silwood CJ, Lynch E, Claxson AW, Grootveld MC. 1H and 13C NMR spectroscopic analysis of human saliva. J Dent Res 2002; 81: 422-27. http://dx.doi.org/10.1177/154405910208100613

Voynow JA, Rubin BK. Mucins, mucus and sputum. Chest 2009; 135: 505-12. http://dx.doi.org/10.1378/chest.08-0412

Fan YG, Hu P, Jiang Y, et al. Association between sputum atypia and lung cancer risk in an occupational cohort in Yunnan, China. Chest 2009; 135: 778-85. http://dx.doi.org/10.1378/chest.08-1469

Kroemer G. Mitochondria in cancer. Oncogene 2006; 25: 4630-32. http://dx.doi.org/10.1038/sj.onc.1209589

Xu RH, Pelicano H, Zhou Y, et al. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia. Cancer Res 2005; 65: 613-21.

Rivenzon-Segal D, Margalit R, Degani H. Glycolysis as a metabolic marker in orthotopic breast cancer, monitored by in vivo 13C MRS. Am J Physiol Endocrinol Metab 2002; 283: E623-30.

Koukourakis MI, Giatromanolaki A, Sivridis E, et al. Tumour and Angiogenesis Research Group. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer 2003; 89: 877-85. http://dx.doi.org/10.1038/sj.bjc.6601205

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Published

2012-01-28

How to Cite

Tedros Bezabeh, Omkar B. Ijare, E. Celia Marginean, & Garth Nicholas. (2012). Proton Magnetic Resonance Spectroscopy of Sputum for the Non-Invasive Diagnosis of Lung Cancer: Preliminary Findings . Journal of Analytical Oncology, 1(1), 14–18. https://doi.org/10.6000/1927-7229.2012.01.01.3

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