Surface-enhanced Raman spectroscopy in women with benign and malignant endometrial diseases

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Abstract

Background. This study aimed to enhance early detection of endometrial cancer in women and distinguish benign conditions from endometrial cancer using surface-enhanced Raman scattering (SERS) analysis of blood plasma, thus increasing diagnostic efficacy.

Materials and methods. The study of blood plasma from 95 female patients aged 22–79 years was performed. The patients were divided into four groups: group 1 included 29 women with endometrial adenocarcinoma, group 2 included 31 patients with endometrial polyp, group 3 included 10 women with endometrial hyperplasia, and the comparison group consisted of 25 healthy women. Blood plasma was analyzed via SERS, with three Raman spectra recorded per sample. Spectral measurements of the SERS substrate were assessed using dried samples on an experimental bench equipped with the spectrometric system RL785 (LLC “Foton-Bio”, Russia), incorporating a CCD detector, laser radiation source with a wavelength of 785 nm, and ADF U300 microscope (ADF, China). A silver substrate composed of dried silver colloid was used to demonstrate the enhancement effect on the Raman signal from the surface of the blood plasma.

Results. Spectral and specific features that distinguish adenocarcinoma, polyps, and endometrial hyperplasia were identified and evaluated. Spectral and quantitative differences specific to each condition, which are crucial for the differential diagnosis of pathologic tissues, were also identified. The accuracy rates of the optical diagnostics in distinguishing endometrial adenocarcinoma from the control group and endometrial hyperplasia were 87% and 85%, respectively, for the calibration and verification spectral sets (where the sensitivity and specificity were 66% and 92% for the spectral verification set, respectively). The accuracy rates of distinguishing control from endometrial hyperplasia and endometrial adenocarcinoma were 86% and 85%, respectively, and the accuracy of distinguishing endometrial hyperplasia from control and endometrial adenocarcinoma was 81% for the calibration and verification sets of spectra. In addition, the study demonstrated improved accuracy in differentiating adenocarcinoma from hyperplasia, including polyps. The accuracy rate was 93% in the calibration set of spectra, with sensitivity and specificity of 96% and 90%, whereas in the validation set, it was 91%, with sensitivity and specificity of 93% and 88%, respectively.

Conclusions. The study demonstrated the potential use of SERS for differentiating expression patterns in endometrial cancer from those in benign conditions.

About the authors

Vladimir M. Zuev

I.M. Sechenov First Moscow State Medicine University (Sechenov University)

Email: vlzuev@bk.ru
ORCID iD: 0000-0001-8715-2020

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Dmitrii V. Lystsev

I.M. Sechenov First Moscow State Medicine University (Sechenov University)

Author for correspondence.
Email: doc.lyscev@gmail.com
ORCID iD: 0009-0006-3826-3174

Graduate Student

Russian Federation, Moscow

Dmitrii N. Artem’ev

Samara National Research University

Email: artemyevdn@ssau.ru
ORCID iD: 0000-0002-1942-8205

Cand. Sci. (Phys.-Mat.), Assistant Professor

Russian Federation, Samara

Lyudmila A. Bratchenko

Samara National Research University

Email: shamina94@inbox.ru

Cand. Sci. (Phys.-Mat.)

Russian Federation, Samara

Vladimir I. Kukushkin

Osipyan Institute of Solid State Physics RAS (ISSP RAS)

Email: kukushvi@mail.ru
ORCID iD: 0000-0001-6731-9508

Cand. Sci. (Phys.-Mat.)

Russian Federation, Chernogolovka

Tat’yana A. Fedorova

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov

Email: t_fyodorova@oparina4.ru
ORCID iD: 0000-0001-6714-6344

MD, Dr. Sci. (Med.), Professor

Russian Federation, Moscow

Oksana A. Bystrykh

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov

Email: ksana.77@inbox.ru

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Anton A. Ishchenko

National Medical Research Center «Treatment and Rehabilitation Center»

Email: ra2001_2001@mail.ru
ORCID iD: 0000-0001-6673-3934

MD, Cand. Sci. (Med.)

Russian Federation, Moscow

Aida V. Gilyadova

I.M. Sechenov First Moscow State Medicine University (Sechenov University); National Medical Research Center «Treatment and Rehabilitation Center»

Email: aida-benyagueva@mail.ru
ORCID iD: 0000-0003-4343-4813

Assistant Lecturer

Russian Federation, Moscow; Moscow

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Supplementary files

Supplementary Files
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2. Fig. 1. Averaged processed spectra of surface-enhanced Raman scattering of blood plasma from samples of patients with endometrial hyperplasia and polyp, as well as endometrial adenocarcinoma in comparison with the control group.

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3. Fig. 2. Distribution of the importance of variables of surface-enhanced Raman plasma spectra in the classification of samples by pathologic-associated trait in the implementation of methods for analyzing experimental data based on PLS-DA: a ― classes: control, polyp + hyperplasia, adenocarcinoma; b ― classes: hyperplasia, adenocarcinoma.

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4. Fig. 3. The accuracy of differentiation of endometrial adenocarcinoma relative to the control group and the group of endometrial hyperplasia + endometrial polyp.

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5. Fig. 4. The accuracy of differentiation of endometrial adenocarcinoma relative to the group of endometrial hyperplasia + endometrial polyp (without the control group).

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