CC BY
0South Russian Journal of Cancer. 2024. Vol. 5, No. 4. P. 14-19 4.0
https://doi.org/10.37748/2686-9039-2024-5-4-2
https://elibrary.ru/udwecg
South Russian
Journal of Cancer ORIGINAL ARTICLE
Южно-Российский
онкологический журнал
Vol. 5
No. 4, 2024 Research on the expression of E-cadherin in lung cancer tumors with
different histological structures
E. N. Kolesnikov, O. N. Stateshny, D. A. Kharagezov, E. A. Mirzoyan, T. G. Ayrapetova,
A. G. Milakin, K. D. Iozefi
National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation
ABSTRACT
Purpose of the study. To conduct a comparative analysis of E-cadherin expression in inoperable patients with non-small cell
lung cancer (NSCLC) cells and with different survival rates.
Materials and methods. The study included 96 patients with inoperable NSCLC: 84 (87.5 %) men and 12 (12.5 %) women,
whose average age was 62.4 ± 0.68 years. Squamous cell carcinoma (SCC) was diagnosed in 78 (81.25 %) patients, and
adenocarcinoma (AC) with a tumor differentiation grade of G2-G3 in 18 (18.75 %). The patients were treated and monitored
at the National Medical Research Centre for Oncology. The expression of cadherins was determined in the tumor cells of the
biopsy specimens. The obtained data have been processed using the Statistica 13.0 program (StatSoftInc., USA). The studied
data have been checked for compliance with the normal distribution using the Shapiro- Wilk criterion.
Results. The following distribution of patients with NSCLC was noted: IIA – 2 (2.1 %), IIB – 14 (14.6 %), IIIA – 51 (53.1 %),
IIIB – 29 (30.2 %), i. e. the frequency of stage III is higher than stage II (83.3 % (n = 80) versus 16.7 % (n = 16), p < 0.001). Fatal
outcome occurred in the SCC group within 1 year in 28 patients, within 1 to 2 years – in 30, 20 patients survived for 3 years or
more. For AC, these figures were 6, 5 and 7 respectively.
The analysis revealed that E-cadherin expression was noted in both squamous cell carcinoma and lung adenocarcinoma: Me
55 [LQ 37; UQ 65] and Me 50 [LQ 40; UQ 70], respectively.
Conclusions. 1. The analysis revealed that E-cadherin expression was observed in both squamous cell carcinoma and lung
adenocarcinomas without statistically significant differences between the compared groups (p = 0.25).
2. Statistically significant differences in the levels of E-cadherin expression were noted in the biopsy samples of the 2 groups
only with survival up to 1 year and up to 3 years or more (p < 0.05).
Keywords: non-small cell lung cancer, chemoradiation therapy, E-cadherin
For citation: Kolesnikov E. N., Stateshny O. N., Kharagezov D. A., Mirzoyan E. A., Ayrapetova T. G., Milakin A. G., Iozefi K. D. Reasearch on the expression of
E-cadherin in lung cancer tumors with different histological structures. South Russian Journal of Cancer. 2024; 5(4): 14-19.
https://doi.org/10.37748/2686-9039-2024-5-4-2, https://elibrary.ru/udwecg
For correspondence: Ellada A. Mirzoyan – Cand. Sci. (Med.), MD, researcher at the Thoracic Department, oncologist at the Department of Thoracic Oncology,
National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation
Address: 63 14 line str., Rostov-on-Don 344037, Russian Federation
E-mail: [email protected]
ORCID: https://orcid.org/0000-0002-0328-9714
SPIN: 2506-8605, AuthorID: 1002948
ResearcherID: AAZ-2780-2021
Scopus Author ID: 57221118516
Compliance with ethical standards: the work was carries out in compliance with the ethical principles set forth by the World Medical Association Declaration
of Helsinki, 1964, ed. 2013. The study was approved by the Committee on Biomedical Ethics at the National Medical Research Center for Oncology, the
Russian Federation Ministry of Health (extract from the protocol of the meeting No. 16 dated 10/12/2021). Informed consents were obtained from all
participants of the study
Funding: this work was not funded
Conflict of interest: the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article
The article was submitted 14.10.2024; approved after reviewing 30.10.2024; accepted for publication 03.11.2024
© Kolesnikov E. N., Stateshny O. N., Kharagezov D. A., Mirzoyan E. A., Ayrapetova T. G., Milakin A. G., Iozefi K. D., 2024
14
Южно-Российский онкологический журнал. 2024. Т. 5, № 4. С. 14-19
https://doi.org/10.37748/2686-9039-2024-5-4-2
https://elibrary.ru/udwecg
3.1.6. Онкология, лучевая терапия
ОРИГИНАЛЬНАЯ СТАТЬЯ
Изучение экспрессии E-кадгерина при немелкоклеточном раке легкого с различным
гистологическим строением
Е. Н. Колесников, О. Н. Статешный, Д. А. Харагезов, Э. А. Мирзоян, Т. Г. Айрапетова, А. Г. Милакин, К. Д. Иозефи
ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения Российской Федерации,
г. Ростов-на-Дону, Российская Федерация
РЕЗЮМЕ
Цель исследования. Провести сравнительный анализ экспрессии E-кадгерина в клетках немелкоклеточного рака
легкого (НМРЛ) неоперабельных больных с разной выживаемостью.
Материалы и методы. В исследование было включено 96 больных НМРЛ: 84 (87,5 %) мужчин и 12 (12,5 %) женщин,
средний возраст которых составил 62,4 ± 0,68 года. У 78 (81,25 %) пациентов диагностирован плоскоклеточный рак
(ПКР), а у 18 (18,75 %) – аденокарцинома (АК) со степенью дифференцировки опухолей G2–G3. Пациенты получали
лечение и находились под наблюдением в ФГБУ «Национальный медицинский исследовательский центр онкологии»
Министерства здравоохранения Российской Федерации. В опухолевых клетках биоптатов определяли экспрессию
кадгеринов. Полученные данные обрабатывали при помощи программы Statistica 13,0 (StatSoftInc., США). Изучаемые
данные проверяли на соответствие нормальному распределению по критерию Шапиро-У илка.
Результаты. Было отмечено следующее распределение больных НМРЛ: IIА – 2 (2,1 %), IIВ – 14 (14,6 %), IIIА – 51 (53,1 %),
IIIВ – 29 (30,2 %), т. е. частота III стадии выше, чем II стадии (83,3 % (n = 80) против 16,7 % (n = 16), p < 0,001). Летальный
исход наступил в группе ПКР в течение 1 года у 28 больных, в период от 1 до 2 лет – у 30, от 2 до 3 лет и более дожили
20 больных. Для АК эти показатели составили 6, 5 и 7 больных соответственно.
При проведении анализа выявлено, что экспрессия Е-кадгерина отмечена как в плоскоклеточном раке, так и в аде-
нокарциномах легкого: Ме 55 [LQ 37; UQ 65] и Me 50 [LQ 40; UQ 70] соответственно.
Заключение. В ходе проведенного анализа выявлено, что экспрессия Е-кадгерина отмечена как в плоскоклеточном
раке, так и в аденокарциномах легкого без статистически значимых различий между сравниваемыми группами
(p = 0,25). Статистически значимые различия по уровням экспрессии Е-кадгерина отмечены в образцах биоптатов
2 групп только с выживаемостью до 1 года и до 3 лет и более (p < 0,05).
Ключевые слова: немелкоклеточный рак легкого, химиолучевое лечение, E-кадгерин
Для цитирования: Колесников Е. Н., Статешный О. Н., Харагезов Д. А., Мирзоян Э. А., Айрапетова Т. Г., Милакин А. Г., Иозефи К. Д. Изучение
экспрессии E-кадгерина при немелкоклеточном раке легкого с различным гистологическим строением. Южно-Российский онкологический
журнал. 2024; 5(4): 14-19. https://doi.org/10.37748/2686-9039-2024-5-4-2, https://elibrary.ru/udwecg
Для корреспонденции: Мирзоян Эллада Арменовна – к.м.н., научный сотрудник торакального отделения, врач-онколог отделения торакальной
онкологии, ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения Российской Федерации,
г. Ростов-на-Дону, Российская Федерация
Адрес: 344037, Российская Федерация, г. Ростов-на-Дону, ул. 14-я линия, д. 63
E-mail: [email protected]
ORCID: https://orcid.org/0000-0002-0328-9714
SPIN: 2506-8605, AuthorID: 1002948
ResearcherID: AAZ-2780-2021
Scopus Author ID: 57221118516
Соблюдение этических стандартов: в работе соблюдались этические принципы, предъявляемые Хельсинкской декларацией Всемирной
медицинской ассоциации (World Medical Association Declaration of Helsinki, 1964, ред. 2013). Исследование одобрено Комитетом по
биомедицинской этике при ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения Российской
Федерации (выписка из протокола заседания № 16 от 12.10.2021 г). Информированное согласие получено от всех участников исследования
Финансирование: финансирование данной работы не проводилось
Конфликт интересов: все авторы заявляют об отсутствии явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи
Статья поступила в редакцию 14.10.2024; одобрена после рецензирования 30.10.2024; принята к публикации 03.11.2024
15
South Russian Journal of Cancer 2024. Vol. 5, No. 4. P. 14-19
Kolesnikov E. N., Stateshny O. N., Kharagezov D. A., Mirzoyan E. A., Ayrapetova T. G., Milakin A. G., Iozefi K. D. Reasearch on the expression of E-cadherin in lung cancer
tumors with different histological structures
INTRODUCTION en, with the average age of 62.4 ± 0.68 years. 78
(81.25 %) patients were diagnosed with squamous
Lung cancer takes the leading 1st place in the cell carcinoma (SCC), and 18 (18.75 %) – adenocar-
structure of general oncological morbidity in the cinoma (AC) with a tissue differentiation grade of
male population [1–3]. Non-small cell lung cancer G2–G3. The following distribution of patients with
(NSCLC) accounts for more than 85 % of cases of NSCLC was noted: IIA – 2 (2.1 %), IIB – 14 (14.6 %),
malignant lung tumors. According to statistics, about IIIA – 51 (53.1 %), IIIB – 29 (30.2 %), i. e. the frequency
40 % of NSCLC cases are diagnosed in stage IV, and of stage III is higher than stage II (83.3 % (n = 80) vs.
25 % in stage III [4]. 16.7 % (n = 16), p < 0.001). Patients underwent si-
The main method of treating NSCLC is surgical [5]. multaneous chemoradiotherapy at doses of 60 Gy
Chemoradiotherapy is usually prescribed due to the in combination with drugs (paclitaxel + carboplatin,
inability to resect the tumor or inoperable patients, pemetrexed + carbolatin) in accordance with stan-
and its effectiveness is assessed by the overall and dards and clinical recommendations for the treat-
event-free survival of patients [6]. ment of lung cancer [5].
Recently, research based on the study of genetic The expression of cadherins was being deter-
characteristics, expression of various receptors has mined in tumor cells of biopsy tissue samples.
become widespread. These can potentially be the To determine the expression of molecular markers
targets for targeted drugs and checkpoint inhibitors. by NSCLC tumor cells, the IHC method was used with
These targets may have prognostic significance in primary monoclonal and polyclonal antibodies, the
the application of various treatment methods [7]. characteristics of which are shown in the Table 1.
It is known that the process of metastasis begins The UltraVision Quanto Detection System HRP
with a violation of epithelial integrity, which leads to DAB was used to visualize the results. The results
the fact that tumor cells begin to penetrate into the of the immunohistochemical reaction were evalu-
surrounding stroma, blood and lymph vessels, and ated using an AxioLab.A1 light microscope (Ger-
infiltrate other organs. many) with lens magnification of ×200, ×400. The
E-cadherin is a transmembrane glycoprotein that is data obtained were processed using the Statistica
closely associated with the occurrence, invasion and 13.0 program (StatSoftInc., USA). The studied data
metastasis of cancer [8]. It can promote adhesion be- were checked for compliance with the normal dis-
tween epithelial cells and maintain the integrity of the tribution according to the Shapiro- Wilk criterion.
tissue structure, which is a deterrent to tumor metas- Since the primary data did not obey the law of
tasis. A decrease or loss of its expression weakens the normal distribution, the comparison of groups was
adhesion between tumor cells, which leads to tumor carried out using the nonparametric Mann- Whitney
metastasis [9]. Today, there are a number of studies criterion (U-criterion): The median (Me), lower and
devoted to the clinical and pathological features and upper quartiles (Q1–Q3) were calculated. The dif-
prognosis of E-cadherin and non-small cell lung cancer, ferences were considered statistically significant
but the results are uneven. According to some authors, at p < 0.05.
low expression of E-cadherin does not contribute to
prognosis in patients with NSCLC [10], while others STUDY RESULTS AND DISCUSSION
believe that the expression of E-cadherin is not associ-
ated with the prognosis of the clinical course [11, 12]. The fatal outcome occurred in the SCC group with-
The purpose of the study was to conduct a com- in 1 year in 28 patients, within 1 to 2 years in 30, and
parative analysis of the expression of E-cadherin in 20 patients lived to 3 or more years. For AC patients,
the lung NSCLC cells of patients, depending on the these figures were 6, 5 and 7, respectively.
histological type of tumor and clinical course. The analysis revealed that the expression of
E-cadherin was noted in both squamous cell car-
MATERIALS AND METHODS cinoma and lung adenocarcinomas: Me 55 [LQ 37;
UQ 65] and Me 50 [LQ 40; UQ 70], respectively. There
The study included 96 patients with inoperable were no statistically significant differences between
NSCLC: 84 (87.5 %) men and 12 (12.5 %) wom- the compared groups (p = 0.25) (Fig. 1).
16
Южно-Российский онкологический журнал 2024. Т. 5, № 4. С. 14-19
Колесников Е. Н., Статешный О. Н., Харагезов Д. А., Мирзоян Э. А., Айрапетова Т. Г., Милакин А. Г., Иозефи К. Д. Изучение экспрессии E-кадгерина при
немелкоклеточном раке легкого с различным гистологическим строением
Table 1 and Figure 2A, B reflect the features of E-cedherin
120
E-cadherin expression in squamous cell carcinomas
and adenocarcinomas in patients with different sur- 100
vival rates.
80
Analyzing the obtained data, it was found that
statistically significant differences in the expression 60
levels of E-cadherin were observed in biopsy samples
40
of 2 groups only with a survival rate of up to 1 year
and up to 3 years or more. 20
In the paperwork of Gkogkou P. et al. the expres-
0
sion levels of E-cadherin and syndecan-1 (SDC1)
were determined in tissue samples of 64 patients
Squamous cell carcinoma Adenocarcinoma
with stage III disease at the time of treatment.
Thus, the negative expression of SDC1 correlated
with squamous cell histology (p = 0.002). Positive Fig. 1. Expression of E-cadherin in tumor samples taken from
expression of E-cadherin was significantly associat- NSCLC patients
ed with an increase in overall survival rate (OS) over
2 years (p = 0.032). E-cadherin expression was an
Table 1. Comparative characteristics of E-cadherin expression in squamous cell carcinomas and adenocarcinomas in patients
with different survival rates
Survival rate
Expression levels % Up to 1 year (I) 1 to 2 years (II) 2 to 3 years (III)
p-value
Me Q1–Q3 Me Q1–Q3 Me Q1–Q3
Squamous cell (I–II) = 0.089
carcinoma 43 40–62.5 55 30–65 65 45–67.5 *(I–III) = 0.04
(II–III) = 0.134
(I–II) = 0.158
Adenocarcinoma 48 32–61 61 48–67 85 52–91.5 *(I–III) = 0.0126
(II–III) = 0.084
Note: * – statistically significant differences between the parameters of the subgroups (p < 0.05)
SCC AC
80 120
70 100
60
80
50
40 60
30 40
20
20
10
А B
0 0
Up to 1 year Up to 2 years Up to 3 years Up to 1 year Up to 2 years Up to 3 years
Fig. 2. Expression of E-cadherin in patients with NSCLC with varying survival rates. A – SCC; B – AC
17
The percent of stained cells
The percent of stained cells The percent of stained cells
South Russian Journal of Cancer 2024. Vol. 5, No. 4. P. 14-19
Kolesnikov E. N., Stateshny O. N., Kharagezov D. A., Mirzoyan E. A., Ayrapetova T. G., Milakin A. G., Iozefi K. D. Reasearch on the expression of E-cadherin in lung cancer
tumors with different histological structures
independent predictor of overall survival (p = 0.007) CONCLUSIONS
and progression-free survival (p = 0.029). The results
obtained by the authors show that positive expres- 1. During the carried out analysis, it was revealed
sion of E-cadherin was associated with an increase that increased expression of E-cadherin was noted in
in overall survival, as well as progression-free sur- both squamous cell carcinomas and lung adenocar-
vival [13]. cinomas without statistically significant differences
L.-Y. He and the authors studied the relationship between the compared groups (p = 0.25).
between E-cadherin and Ki-67 and their clinical sig- 2. Statistically significant differences in E-cadherin
nificance in NSCLC. The correlation analysis revealed expression levels were noted in biopsy samples of
an inverse relationship between the expression of the compared groups only with survival range up to 1
E-cadherin and Ki-67 (r = 0.524, p = 0.000). Clinical year and up to 3 years or more (p < 0.05). According
and pathological characteristics (grade, TNM stage, to other criteria, there were no statistically significant
lymph node metastases and pleural invasion) were differences.
significantly associated with the expression of E-cad
and Ki-67 (p < 0.05). The authors concluded that SUMMARY
E-cadherin and Ki-67 together play a key role in the
development, invasion and metastasis of NSCLC, and Therefore, E-cadherin may be a prognostic factor
their joint detection serves as a potential marker for for overall survival and progression-free survival in
clinical diagnosis in addition to use as a therapeutic patients with NSCLC, and its combination with Ki-67
target [14]. may be used as a potential therapeutic target.
References
1. Kit OI, Turkin IN, Kharagezov DA, Lazutin YuN, Leiman IA, Chubaryan AV, et al. Sequential bronchoplastic upper lobectomy
as a surgical component of multimodal treatment for synchronous bilateral multiple primary non-small cell lung cancer.
Siberian Journal of Oncology. 2022;21(3):143−150. (In Russ.). https://doi.org/10.21294/1814-4861-2022-21-3-143-150
2. The state of cancer care for the Russian population in 2023. Edited by A. D. Kaprin, V. V. Starinsky, A. O. Shakhzadova Mos-
cow: P. A. Herzen MNIOI – Branch of the National Medical Research Radiological Center, 2024, 262 p. (In Russ.).
3. Iozefi KD, Kharagezov DA, Lazutin YuN, Mirzoyan EA, Hayrapetova TG, Leyman IA, et al. Intraoperative pleurodesis as a way
to prevent prolonged air leakage after anatomical lung resections for cancer. Modern Problems of Science and Education.
(In Russ.). 2024;(1):27. https://doi.org/10.17513/spno.33286, EDN: NMZYZG
4. Price A. Emerging developments of chemoradiotherapy in stage III NSCLC. Nature Reviews Clinical Oncology. 2013;9(10):
591–598. https://doi.org/10.1038/nrclinonc.2012.135.
5. Malignant neoplasm of the bronchi and lung. Clinical Recommendations. 2021, 116 p. Available at: https://oncology-asso-
ciation.ru/wp-content/uploads/2021/02/rak-legkogo-2021.pdf?ysclid=m3gxqlmm8k225907433, Accessed: 24.10.2024.
6. Laktionov KK, Artamonova EV, Borisova TN, Breder VV, Bychkov YuM, Vladimirova LYu, et al. Malignant neoplasm of the
bronchi and lung. Modern Oncology. 2021;23(3):369–402. (In Russ.). https://doi.org/10.26442/18151434.2021.3.20104,
EDN: NPNNMP
7. Faurobert E, Bouin AP, Albiges-Rizo C. Microenvironment, tumor cell plasticity, and cancer. Curr Opin Oncol. 2015
Jan;27(1):64–70. https://doi.org/10.1097/CCO.0000000000000154
8. Edwards LA, Woolard K, Son MJ, Li A, Lee J, Ene C, et al. Effect of brain- and tumor-derived connective tissue growth factor
on glioma invasion. J Natl Cancer Inst. 2011 Aug 3;103(15):1162–1178. https://doi.org/10.1093/jnci/djr224
9. Hornsveld M, Tenhagen M, van de Ven RA, Smits AMM, van Triest MH, van Amersfoort M, et al. Restraining FOXO3-depen-
dent transcriptional BMF activation underpins tumour growth and metastasis of E-cadherin-negative breast cancer. Cell
Death Differ. 2016 Sep 1;23(9):1483–1492. https://doi.org/10.1038/cdd.2016.33
10. Deeb G, Wang J, Ramnath N, Slocum HK, Wiseman S, Beck A, et al. Altered E-cadherin and epidermal growth factor receptor
expressions are associated with patient survival in lung cancer: a study utilizing high-density tissue microarray and immu-
nohistochemistry. Mod Pathol. 2004 Apr;17(4):430–439. https://doi.org/10.1038/modpathol.3800041
18
Южно-Российский онкологический журнал 2024. Т. 5, № 4. С. 14-19
Колесников Е. Н., Статешный О. Н., Харагезов Д. А., Мирзоян Э. А., Айрапетова Т. Г., Милакин А. Г., Иозефи К. Д. Изучение экспрессии E-кадгерина при
немелкоклеточном раке легкого с различным гистологическим строением
11. Yamashita T, Uramoto H, Onitsuka T, Ono K, Baba T, So T, et al. Association between lymphangiogenesis-/micrometasta-
sis- and adhesion-related molecules in resected stage I NSCLC. Lung Cancer. 2010 Dec;70(3):320–328.
https://doi.org/10.1016/j.lungcan.2010.02.013
12. Zhang H, Liu J, Yue D, Gao L, Wang D, Zhang H, et al. Clinical significance of E-cadherin, β-catenin, vimentin and S100A4
expression in completely resected squamous cell lung carcinoma. J Clin Pathol. 2013 Nov;66(11):937–945.
https://doi.org/10.1136/jclinpath-2013-201467
13. Gkogkou P, Peponi E, Ntaskagiannis D, Murray S, Demou A, Sainis I, et al. E-Cadherin and Syndecan-1 Expression in Patients
With Advanced Non-small Cell Lung Cancer Treated With Chemoradiotherapy. In Vivo. 2020;34(1):453–459.
https://doi.org/10.21873/invivo.11795
14. He LY, Zhang H, Wang ZK, Zhang HZ. Diagnostic and prognostic significance of E-cadherin and Ki-67 expression in non-
small cell lung cancer patients. Eur Rev Med Pharmacol Sci. 2016 Sep;20(18):3812–3817.
Information about authors:
Evgenii N. Kolesnikov – Dr. Sci. (Med.), MD, associate professor, head of the Department of Abdominal Oncology No. 1, National Medical Research
Centre for Oncology, Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0001-9749-709X, SPIN: 8434-6494, AuthorID: 347457, Scopus Author ID: 57190297598
Oleg N. Stateshny – MD, oncologist at the Department of Thoracic Oncology, National Medical Research Centre for Oncology, Rostov-on-Don,
Russian Federation
ORCID: https://orcid.org/0000-0003-4513-7548, SPIN: 9917-1975, AuthorID: 1067071
Dmitriy A. Kharagezov – Cand. Sci. (Med.), MD, head of the Department of Thoracic Oncology, National Medical Research Centre for Oncology,
Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0003-0640-2994, SPIN: 5120-0561, AuthorID: 733789, ResearcherID: AAZ-3638-2021, Scopus Author ID: 56626499300
Ellada A. Mirzoyan – Cand. Sci. (Med.), MD, researcher at the Thoracic Department, oncologist at the Department of Thoracic Oncology, National
Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0002-0328-9714, SPIN: 2506-8605, AuthorID: 1002948, ResearcherID: AAZ-2780-2021, Scopus Author ID: 57221118516
Tamara G. Ayrapetova – Cand. Sci. (Med.), PhD, MD, oncologist at the Department of Thoracic Oncology, National Medical Research Centre for
Oncology, Rostov-on-Don, Russian Federation
ORCID: https://orcid.org/0000-0001-5287-5800, SPIN: 8121-4039, AuthorID: 794672
Anton G. Milakin – MD, oncologist at the Department of Thoracic Oncology, National Medical Research Centre for Oncology, Rostov-on-Don,
Russian Federation
ORCID: https://orcid.org/0000-0002-2589-7606, SPIN: 7737-4737, AuthorID: 794734
Kristian D. Iozefi – MD, thoracic surgeon at the Department of Thoracic Oncology, National Medical Research Centre for Oncology, Rostov-on-Don,
Russian Federation
ORCID: https://orcid.org/0000-0002-5351-3251, SPIN: 1232-3097, AuthorID: 1122592, ResearcherID: AAZ-3632-2021
Contribution of the authors:
Kolesnikov E. N., Kharagezov D. A – scientific management;
Stateshny O. N., Mirzoyan E. A. – writing the draft, material processing;
Ayrapetova T. G., Milakin A. G, Iozefi K. D. – data collection and analysis, technical formatting, bibliography design.
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