Open Access

Metabolomic profiling of breast tumors using ductal fluid

  • Authors:
    • Luisa Matos Do Canto
    • Catalin Marian
    • Rency S. Varghese
    • Jaeil Ahn
    • Patricia A. Da Cunha
    • Shawna Willey
    • Mary Sidawy
    • Janice D. Rone
    • Amrita K. Cheema
    • George Luta
    • Mohammad R. Nezami Ranjbar
    • Habtom W. Ressom
    • Bassem R. Haddad
  • View Affiliations

  • Published online on: October 13, 2016     https://doi.org/10.3892/ijo.2016.3732
  • Pages: 2245-2254
  • Copyright: © Matos Do Canto et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Identification of new biomarkers for breast cancer remains critical in order to enhance early detection of the disease and improve its prognosis. Towards this end, we performed an untargeted metabolomic analysis of breast ductal fluid using an ultra-performance liquid chromatography coupled with a quadrupole time-of-light (UPLC-QTOF) mass spectrometer. We investigated the metabolomic profiles of breast tumors using ductal fluid samples collected by ductal lavage (DL). We studied fluid from both the affected breasts and the unaffected contralateral breasts (as controls) from 43 women with confirmed unilateral breast cancer. Using this approach, we identified 1560 ions in the positive mode and 538 ions in the negative mode after preprocessing of the UPLC‑QTOF data. Paired t-tests applied on these data matrices identified 209 ions (positive and negative modes combined) with significant change in intensity level between affected and unaffected control breasts (adjusted p-values <0.05). Among these, 83 ions (39.7%) showed a fold change (FC) >1.2 and 66 ions (31.6%) were identified with putative compound names. The metabolites that we identified included endogenous metabolites such as amino acid derivatives (N-Acetyl-DL-tryptophan) or products of lipid metabolism such as N-linoleoyl taurine, trans-2-dodecenoylcarnitine, lysophosphatidylcholine LysoPC(18:2(9Z,12Z)), glycerophospholipids PG(18:0/0:0), and phosphatidylserine PS(20:4(5Z,8Z,11Z,14Z). Generalized LASSO regression further selected 21 metabolites when race, menopausal status, smoking, grade and TNM stage were adjusted for. A predictive conditional logistic regression model, using the LASSO selected 21 ions, provided diagnostic accuracy with the area under the curve of 0.956 (sensitivity/specificity of 0.907/0.884). This is the first study that shows the feasibility of conducting a comprehensive metabolomic profiling of breast tumors using breast ductal fluid to detect changes in the cellular microenvironment of the tumors and shows the potential for this approach to be used to improve detection of breast cancer.
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December-2016
Volume 49 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
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Spandidos Publications style
Matos Do Canto L, Marian C, Varghese RS, Ahn J, Da Cunha PA, Willey S, Sidawy M, Rone JD, Cheema AK, Luta G, Luta G, et al: Metabolomic profiling of breast tumors using ductal fluid. Int J Oncol 49: 2245-2254, 2016.
APA
Matos Do Canto, L., Marian, C., Varghese, R.S., Ahn, J., Da Cunha, P.A., Willey, S. ... Haddad, B.R. (2016). Metabolomic profiling of breast tumors using ductal fluid. International Journal of Oncology, 49, 2245-2254. https://doi.org/10.3892/ijo.2016.3732
MLA
Matos Do Canto, L., Marian, C., Varghese, R. S., Ahn, J., Da Cunha, P. A., Willey, S., Sidawy, M., Rone, J. D., Cheema, A. K., Luta, G., Nezami Ranjbar, M. R., Ressom, H. W., Haddad, B. R."Metabolomic profiling of breast tumors using ductal fluid". International Journal of Oncology 49.6 (2016): 2245-2254.
Chicago
Matos Do Canto, L., Marian, C., Varghese, R. S., Ahn, J., Da Cunha, P. A., Willey, S., Sidawy, M., Rone, J. D., Cheema, A. K., Luta, G., Nezami Ranjbar, M. R., Ressom, H. W., Haddad, B. R."Metabolomic profiling of breast tumors using ductal fluid". International Journal of Oncology 49, no. 6 (2016): 2245-2254. https://doi.org/10.3892/ijo.2016.3732