Relative quantitation of phosphatidylcholines with interfered masses of protonated and sodiated molecules by tandem and Fourier-transform ion cyclotron resonance mass spectrometry

Chagovets, Vitaliy; Кононихин, А. С.; Tokoreva, Alisa; Bormotov, Denis S.; Стародубцева, Н. Л.; Kostyukevich, Yury; Popov, Igor; Frankevich, Vladimir; Nikolaev, Eugene

doi:10.1177/1469066718799992

Cited by 4 publications

(7 citation statements)

References 16 publications

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“…MS analysis of tissue samples is performed on Maxis Impact qTOF (Bruker Daltonics, Bremen, Germany) with the in-lab designed ion source for tissue spray MS [28]. A mixture of H 2 O/methanol 1/9 with 0.1% formic acid is used for online tissue extraction and following spraying [30,31]. The solvent is supplied to the tissue with a flow rate of 1 mL/min by Dionex binary pump (Thermo Scientific, Germering, Germany).…”

Section: Tissue Spray Mass Spectrometry Of Breast Samplesmentioning

confidence: 99%

“…Lipid peaks are typically dominated in tissue spray mass spectra [24][25][26], therefore, R-scripts generating theoretical lipid masses are developed to identify the obtained spectra. The possibility of ion formation by protons, sodium cation or potassium cation attachment in the positive ion mode is considered [29][30][31][32]. Deprotonation and chloride anion attachment are considered in the negative ion mode.…”

Section: Tissue Spray Ms Datamentioning

confidence: 99%

“…In our laboratory we are developing tissue spray mass spectrometry for the study of lipid markers of endometriosis tissues, lung cancer, and brain tumors [24][25][26][27][28][29][30][31]. The complete obviation of sample preparation and chromatographic separation stages allows rapid analysis without significant loss of chemical information [32].…”

Section: Introductionmentioning

confidence: 99%

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Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry

Chagovets

Стародубцева

Tokareva

et al. 2020

IJMS

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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.

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Section: Tissue Spray Mass Spectrometry Of Breast Samplesmentioning

confidence: 99%

Section: Tissue Spray Ms Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry

Chagovets

Стародубцева

Tokareva

et al. 2020

IJMS

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“…Shotgun lipidomics based on electrospray ionization mass spectrometry (ESI-MS) allows deep molecular profiling of a sample without significant losses of chemical information [26,27]. The high diagnostic potential of lipidomics has been shown in many areas of medicine, particularly in oncology: lung, thyroid gland, breast, stomach, pancreas, colorectal, liver, kidney, prostate, ovarian, and endometrium cancer [28,29,[38][39][40][41][42][43][44][45][46][47]30,[48][49][50][51][31][32][33][34][35][36][37]. MS studies of lipid profiles in tissues and blood plasma have revealed new promising biomarkers of endometriosis (benign gynecological disorder) [26,27,32,33,37,44,47].…”

Section: Introductionmentioning

confidence: 99%

Alterations in Lipid Profile Upon Uterine Fibroids and Its Recurrence

Tonoyan

Chagovets

Стародубцева

et al. 2021

Preprint

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Background. Uterine fibroids (UF) is the most common (about 70% cases) type of gynecological disease, with the recurrence rate varying from 11% to 40%. Because UF has no distinct symptomatology and is often asymptomatic, the specific and sensitive diagnosis of UF as well as the assessment for the probability of UF recurrence pose considerable challenge.Aim. The aim of this study was to characterize alterations in the lipid profile of tissues associated with the first-time diagnosed UF and recurrent uterine fibroids (RUF) and to explore the potential of mass spectrometry (MS) lipidomics analysis of blood plasma samples for the sensitive and specific determination of UF and RUF with low invasiveness of analysis.Materials and methods. MS analysis of lipid levels in the myometrium tissues, fibroids tissues and blood plasma samples was carried out on 66 patients, including35 patients with first-time diagnosed UF and 31 patients with RUF. The control group consisted of 15 patients who underwent surgical treatment for the intrauterine septum. Fibroids and myometrium tissue samples were analyzed using direct MS approach. Blood plasma samples were analyzed using high performance liquid chromatography hyphened with mass spectrometry (HPLC/MS). MS data were processed by discriminant analysis with projection into latent structures (OPLS-DA).Results. Significant differences were found between the first-time UF, RUF and control group in the levels of lipids involved in the metabolism of glycerophospholipids, sphingolipids, lipids with an ether bond, triglycerides and fatty acids. Significant differences between the control group and the groups with UF and RUF were found in the blood plasma levels of cholesterol esters, triacylglycerols, (lyso) phosphatidylcholines and sphingomyelins. Significant differences between the UF and RUF groups were found in the blood plasma levels of cholesterol esters, phosphotidylcholines, sphingomyelins and triacylglycerols. Diagnostic models based on the selected differential lipids using logistic regression showed sensitivity and specificity of 88% and 86% for the diagnosis of first-time UF and 95% and 79% for RUF, accordingly.Conclusion. This study confirms the involvement of lipids in the pathogenesis of uterine fibroids. A diagnostically significant panel of differential lipid species has been identified for the diagnosis of UF and RUF by low-invasive blood plasma analysis. The developed diagnostic models demonstrated high potential for clinical use and further research in this direction.

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“…Lipids are biologically active compounds that regulate a number of important cellular processes, incuding proliferation, apoptosis, and angiogenesis 8 . Differences in the lipid pro le of a tissue allow the identi cation of benign and malignant processes in the tissue [9][10][11][12][13][14][15] . High performance liquid chromatography combined with mass spectrometry (HPLC-MS) is regarded to be the most informative method for lipid analysis 16 .…”

Section: Introductionmentioning

confidence: 99%

Lipid Markers of Breast Tissue for the Diagnosis of Regional Metastatic Lesion

Chagovets¹,

Tokareva²,

Стародубцева³

et al. 2021

Preprint

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The development of minimally invasive, non-traumatic and stable approaches for the diagnosis of metastatic lesions of regional lymph nodes upon breast cancer is of great urgency. Here we recorded lipid profiles of normal breast tissue and malignant tissue to reveal potential lipid markers of metastatic lesions of regional lymph nodes. Lipid identification was done using the Lipid Match package. The search for lipid markers was carried out using the Mann-Whitney test. Lipids for the construction of a diagnostic logistic regression were selected according to the Akaike information criterion. For normal breast tissue, a diagnostic model was obtained with the area under the curve (AUC) of 0.83; for tumor tissue, a model with AUC = 0.86 was obtained. The species PC 14:0_20:4, PE 18:1_20:1, PC P-16:0/20:4, PC P-16:0/20:4, PE P-16:0/22:4, SM d18:1/18 0, SM d18:1/22:0 were determined as markers for normal breast tissue. The species PC 18:2_22:6, PC O-18:0/20:2, SM d16:1/18:1, SM d22:0/20:2, SM d16:0/18:2 were determined as markers for tumor tissue. The high AUC values for the developed diagnostic model indicate the potential significance of the revealed marker species for the diagnosis of breast cancer metastasis and indicate the need for further research in this direction.

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Relative quantitation of phosphatidylcholines with interfered masses of protonated and sodiated molecules by tandem and Fourier-transform ion cyclotron resonance mass spectrometry

Cited by 4 publications

References 16 publications

Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry

Validation of Breast Cancer Margins by Tissue Spray Mass Spectrometry

Alterations in Lipid Profile Upon Uterine Fibroids and Its Recurrence

Lipid Markers of Breast Tissue for the Diagnosis of Regional Metastatic Lesion

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