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Article

Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry

1
National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia
2
Moscow Institute of Physics and Technology, 141701 Moscow, Russia
3
V.L. Talrose Institute for Energy Problems of Chemical Physics, Russia Academy of Sciences, 119991 Moscow, Russia
4
Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang 330013, China
5
Department of Obstetrics, Gynecology, Perinatology and Reproductology, First Moscow State Medical University named after I.M. Sechenov, 119991 Moscow, Russia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(12), 4568; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124568
Received: 10 June 2020 / Revised: 23 June 2020 / Accepted: 24 June 2020 / Published: 26 June 2020
(This article belongs to the Special Issue Breast Cancer: From Pathophysiology to Novel Therapeutic Approaches)
Current methods for the intraoperative determination of breast cancer margins commonly suffer from the insufficient accuracy, specificity and/or low speed of analysis, increasing the time and cost of operation as well the risk of cancer recurrence. The purpose of this study is to develop a method for the rapid and accurate determination of breast cancer margins using direct molecular profiling by mass spectrometry (MS). Direct molecular fingerprinting of tiny pieces of breast tissue (approximately 1 × 1 × 1 mm) is performed using a home-built tissue spray ionization source installed on a Maxis Impact quadrupole time-of-flight mass spectrometer (qTOF MS) (Bruker Daltonics, Hamburg, Germany). Statistical analysis of MS data from 50 samples of both normal and cancer tissue (from 25 patients) was performed using orthogonal projections onto latent structures discriminant analysis (OPLS-DA). Additionally, the results of OPLS classification of new 19 pieces of two tissue samples were compared with the results of histological analysis performed on the same tissues samples. The average time of analysis for one sample was about 5 min. Positive and negative ionization modes are used to provide complementary information and to find out the most informative method for a breast tissue classification. The analysis provides information on 11 lipid classes. OPLS-DA models are created for the classification of normal and cancer tissue based on the various datasets: All mass spectrometric peaks over 300 counts; peaks with a statistically significant difference of intensity determined by the Mann–Whitney U-test (p < 0.05); peaks identified as lipids; both identified and significantly different peaks. The highest values of Q2 have models built on all MS peaks and on significantly different peaks. While such models are useful for classification itself, they are of less value for building explanatory mechanisms of pathophysiology and providing a pathway analysis. Models based on identified peaks are preferable from this point of view. Results obtained by OPLS-DA classification of the tissue spray MS data of a new sample set (n = 19) revealed 100% sensitivity and specificity when compared to histological analysis, the “gold” standard for tissue classification. “All peaks” and “significantly different peaks” datasets in the positive ion mode were ideal for breast cancer tissue classification. Our results indicate the potential of tissue spray mass spectrometry for rapid, accurate and intraoperative diagnostics of breast cancer tissue as a means to reduce surgical intervention. View Full-Text
Keywords: direct mass spectrometry; lipidomics; breast cancer; tissue spray; molecular profiling; discriminant model direct mass spectrometry; lipidomics; breast cancer; tissue spray; molecular profiling; discriminant model
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MDPI and ACS Style

Chagovets, V.V.; Starodubtseva, N.L.; Tokareva, A.O.; Frankevich, V.E.; Rodionov, V.V.; Kometova, V.V.; Chingin, K.; Kukaev, E.N.; Chen, H.; Sukhikh, G.T. Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry. Int. J. Mol. Sci. 2020, 21, 4568. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124568

AMA Style

Chagovets VV, Starodubtseva NL, Tokareva AO, Frankevich VE, Rodionov VV, Kometova VV, Chingin K, Kukaev EN, Chen H, Sukhikh GT. Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry. International Journal of Molecular Sciences. 2020; 21(12):4568. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124568

Chicago/Turabian Style

Chagovets, Vitaliy V., Natalia L. Starodubtseva, Alisa O. Tokareva, Vladimir E. Frankevich, Valerii V. Rodionov, Vlada V. Kometova, Konstantin Chingin, Eugene N. Kukaev, Huanwen Chen, and Gennady T. Sukhikh 2020. "Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry" International Journal of Molecular Sciences 21, no. 12: 4568. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124568

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