EXPRESSION OF KISSPEPTIN IN LUNG CARCINOMA AS AN INDICATOR OF TUMOR PROGRESSION

DOI: https://doi.org/10.29296/24999490-2023-05-03

Do Ngoc Hop(1, 2, 3), E.S. Mironova(1, 4), I.M. Kvetnoy(1, 2), M.A. Dokhov(1, 5), M.A. Paltsev(6)
1-St. Petersburg Research Institute of Phthisiopulmonology, Ministry of Health of the Russian Federation,
Ligovsky Ave., 2–4, St. Petersburg, 191036, Russian Federation; 2-FGBOU HE "St. Petersburg State University",
Universitetskaya nab., 7/9, St. Petersburg, 199034, Russian Federation;
3-Vietnamese Military Medical Academy,
st. Phung Hung, 160, Hanoi, Vietnam;
4-ANNO VO Research Center "St. Petersburg Institute of Bioregulation and Gerontology",
Dynamo Ave., 3, St. Petersburg, 197110, Russian Federation;
5-Federal State Budgetary Educational Institution of Higher Education
"St. Petersburg State Pediatric Medical University" of the Ministry of Health of the Russian Federation,
st. Litovskaya, 2, St. Petersburg, 194100, Russian Federation;
6-Federal State Budgetary Educational Institution of Higher Education "Moscow State University named after. M.V. Lomonosov",
Leninskie Gory, 1, Moscow, 119991, Russian Federation

Introduction. Lung carcinoma is one of the most common cancers and the most likely cause of cancer mortality in the world. The use of the IHC method to determine the immunophenotype of tumor cells greatly facilitates the differential diagnostic search, allows us to identify the pathogenetic mechanisms of tumor progression and molecular targets for the selection of modern and most effective therapy. The KISS1/KISS1R signaling system can serve as a regulator of tumor metastasis and is a potential prognostic marker of tumor processes. In this regard, the relevance of the chosen research topic is to conduct an in-depth study of kisspeptin expression in lung carcinomas to assess the diagnostic and prognostic value of kisspeptins during tumor growth. The purpose of the study was to determine the prognostic value of kisspeptin in lung carcinomas of varying degrees of differentiation. Methods. The material for the study was samples of lung tumors (adenocarcinoma). On fixed tissue, the relative area of KISS1 expression was measured, which was determined by immunohistochemistry. Results. The second degree of tumor differentiation occurred at older ages. A relationship has been established between the degree of tumor differentiation and the relative area of kisspeptin expression. A monotonous increase in the relative area of kisspeptin expression was revealed during the transition from a low to a high degree of differentiation. The relationship between metastasis and the relative area of kisspeptin expression was determined. It has been confirmed that secondary changes (inflammation, hemorrhage and necrosis) occur statistically significantly more often with lymphovascular invasion. Conclusion. The results obtained are the basis for creating an algorithm for using indicators of kisspeptin-1 expression in lung carcinomas as markers for assessing its progression.
Keywords: 
KISS1, kisspeptin, lung cancer, adenocarcinoma, immunohistochemistry, degree of tumor differentiation
Список литературы: 
  1. Thai A.A., Solomon B.J., Sequist L.V. Lung cancer. Lancet. 2021; 398 (10299): 535–54. DOI: 10.1016/s0140-6736(21)00312-3.
  2. World Health Organization. International agency for research on cancer. 2019.
  3. Villalobos P., Wistuba I.I. Lung cancer biomarkers. Hematology/Oncology Clinics. 2017; 31 (1): 13–29. DOI: 10.1016/j.hoc.2016.08.006.
  4. Hirsch F.R., Scagliotti G.V., Mulshine J.L., Kwon R., Curran W.J. Jr., Wu Y.L., Paz-Ares L. Lung cancer: current therapies and new targeted treatments. The Lancet. 2017; 389 (10066): 299–311. DOI: 10.1016/S0140-6736(16)30958-8.
  5. Schabath M.B., Cote M.L. Cancer progress and priorities: lung cancer. Cancer Epidemiology and Prevention Biomarkers. 2019; 28 (10): 1563–79. DOI: 10.1158/1055-9965.EPI-19-0221.
  6. Dubey A.K., Gupta U., Jain S. Epidemiology of lung cancer and approaches for its prediction: a systematic review and analysis. Chinese J. of cancer. 2016; 35 (1): 1–13. DOI: 10.1186/s40880-016-0135-x.
  7. Калинин, Е.А., Сеньчукова М.Д., Литвинов А.А. Рак легкого в Оренбургской области и Российской Федерации (анализ статистических показателей за 2007–2016 гг.). Онкология. Журнал им. ПА Герцена. 2019; 8 (3): 199–207.
  8. [Kalinin E.A., Sen'chukova M.D., Litvinov A.A. Lung cancer in the Orenburg region and the Russian Federation (analysis of statistical indicators for 2007–2016). Onkologiya. Zhurnal im. PA Gercena. 2019; 8 (3): 199–207 (in Russian)].
  9. Савостикова М., Фурминская Е. Цитологическая и иммуноцитохимическая диагностика опухолей легких. Вестник РОНЦ им. НН Блохина РАМН. 2015; 26 (3): 29–38.
  10. [Savostikova M.V., Furminskaya E.Y. Cytologicaland immunocytochemical diagnostics of lung cancer. Vestnik RONC im. NN Blohina RAMN. 2015; 26 (3): 29–38 (in Russian)].
  11. Bodor J.N., Boumber Y., Borghaei H. Biomarkers for immune checkpoint inhibition in non–small cell lung cancer (NSCLC). Cancer. 2020; 126 (2): 260–70. DOI: 10.1002/cncr.32468.
  12. Гуревич Л.Е., Корсакова Н.А., Воронкова И.А., Казанцева И.А., Ашевская В.Е., Титов А.Г., Когония Л.М., Мазурин В.С., Шабаров В.Л. Прогностическое и дифференциально-диагностическое значение экспрессии цитокератинов 7 и 19 и тиреоидного фактора транскрипции-1 в нейроэндокринных опухолях легких разной степени злокачественности. Альманах клинической медицины. 2016; 44 (5): 613–23.
  13. [Gurevich L.E., Korsakova N.A., Voronkova I.A., Kazanceva I.A., Ashevskaya V.E., Titov A.G., Kogoniya L.M., Mazurin V.S., SHabarov V.L. Prognostic and differential-diagnostic significance of the expression of cytokeratins 7 and 19 and thyroid transcription factor-1 in neuroendocrine tumors of the lung of different grades of malignanc. Al'manah klinicheskoj mediciny. 2016; 44 (5): 613–23 (in Russian)].
  14. Vidarsdottir H., Tran L., Nodin B., Jirström K., Planck M., Jönsson P., Mattsson J.S.M., Botling J., Micke P., Brunnström H. Immunohistochemical profiles in primary lung cancers and epithelial pulmonary metastases. Hum Pathol. 2019; 84: 221–30. DOI: 10.1016/j.humpath.2018.10.009.
  15. Пальцев М.А., Дробинцева А.О., Миронова Е.С., Пальцева Е.М., До Нгок Хоп, Новак-Бобарыкина У.А., Леонтьева Д.О. Кисспептины: молекулярные механизмы патологии дыхательной системы. Молекулярная медицина. 2022; 20 (4): 3–8. DOI: 10.29296/24999490-2022-04-01.
  16. [Pal'cev M.A., Drobinceva A.O., Mironova E.S., Pal'ceva E.M., Do Ngok Hop, Novak-Bobarykina U.A., Leont'eva D.O. Kisspeptins: molecular mechanisms of pathology of the respiratory system. Molekulyarnaya medicina. 2022; 20 (4): 3–8. DOI: 10.29296/24999490-2022-04-01. (in Russian)].
  17. Горбунова О., Ширшев С. Роль кисспептина в регуляции репродуктивной и иммунной функций. Биохимия. 2020; 85 (8): 987–1003. DOI: 10.31857/S0320972520080011.
  18. [Gorbunova O., SHirshev S. The role of kisspeptin in the regulation of reproductive and immune functions. Biohimiya. 2020; 85 (8): 987–1003. DOI: 10.31857/S0320972520080011. (in Russian)].
  19. Родичкина В.Р., Клейменова Т.С., Дробинцева А.О., Полякова В.О., Костюченко Р.П., Кветной И.М. Иммуногистохимическая верификация кисспептинов и их рецептора в органах плода человека в период внутриутробного развития. Онтогенез. 2017; 48 (3): 203–10. DOI: 10.7868/S0475145017030107.
  20. [Rodichkina V.R., Klejmenova T.S., Drobinceva A.O., Polyakova V.O., Kostyuchenko R.P., Kvetnoj I.M. Immunohistochemical verification of kisspeptins and their receptor in human fetal organs during fetal development. Ontogenez. 2017; 48 (3): 203–10. DOI: 10.7868/S0475145017030107. (in Russian)].
  21. Мнихович М.В., Безуглова Т.В., Кактурский Л.В., Буньков К.В., Тучкова А.С., Трифонов М.И., Мишина Е.С. Сигнальная система KISS1/KISS1R и ее роль в канцерогенезе. Гены и клетки. 2019; 14 (3): 124–30. DOI: 10.23868/201906022.
  22. [Mnihovich M.V., Bezuglova T.V., Kakturskij L.V., Bun'kov K.V., Tuchkova A.S., Trifonov M.I., Mishina E.S. The KISS1/KISS1R signaling system and its role in carcinogenesis. Geny i kletki. 2019; 14 (3): 124–30. DOI: 10.23868/201906022. (in Russian)].