medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2024-7-55-59medalphabet-3689Research ArticleДИАГНОСТИКА И ОНКОТЕРАПИЯDIAGNOSTICS AND ONCOTHERAPYВитамины группы В и гомоцистеин у онкологических пациентов с солидными злокачественными новообразованиями до назначения химиотерапииB vitamins and homocysteine in cancer patients with solid malignancies before chemotherapy administrationhttps://orcid.org/0000-0002-1796-0193ТихоноваО. А.TikhonovaO. A.

Тихонова Ольга Алексеевна - врач-невролог, аспирант, ассистент кафедры психиатрии и нейронаук 

г. Калининград

Tikhonova Olga A.  - neurologist, postgraduate student, assistant at Dept of Psychiatry and Neurosciences

Kaliningrad

offelia78@mail.ruhttps://orcid.org/0000-0002-6244-0867ДружининД. С.DruzhininD. S.

Дружинин Дмитрий Сергеевич - д.м.н., ассистент кафедры нервных болезней с медицинской генетикой и нейрохирургией

г. Ярославль

Druzhinin Dmitry S. - DM Sci (habil.), assistant at Dept of Nervous Diseases with Medical Genetics and Neurosurgery

Yaroslavl

druzhininds@gmail.comhttps://orcid.org/0000-0001-5231-6910ЛитвиноваЛ. С.LitvinovaL. S.

Литвинова Лариса Сергеевна - д.м.н., директор Центра иммунологии и клеточных биотехнологий

г. Калининград

Litvinova Larisa S. - DM Sci (habil.), head of Center for Immunology and Cellular Biotechnology

Kaliningrad

larisalitvinova@yandex.ruhttps://orcid.org/0000-0001-5858-7877ДоктороваС. А.DoktorovaS. A.

Докторова Светлана Алексеевна - врач-клинический фармаколог, аспирант специальности «Фармакология, клиническая фармакология»

г. Калининград

Doktorova Svetlana A. - clinical pharmacologist, postgraduate student, specialty «Pharmacology, Clinical Pharmacology

Kaliningrad

svdoktorova96@gmail.comhttps://orcid.org/0000-0001-7468-4861ТодосенкоН. М.TodosenkoN. M.

Тодосенко Наталья Михайловна - к.б.н., с.н.с. Центра иммунологии и клеточных биотехнологий

г. Калининград

Todosenko Natalia M. - PhD Bio Sci, senior researcher at Center for Immunology and Cellular Biotechnology

Kaliningrad

tod_89@mail.ruhttps://orcid.org/0000-0002-4646-3436ГазатоваН. Д.GazatovaN. D.

Газатова Наталья Динисламовна - к.б.н., ст.н.с. Центра иммунологии и клеточных биотехнологий

г. Калининград

Gazatova Natalia D. - PhD Bio Sci, senior researcher at Center for Immunology and Cellular Biotechnology

Kaliningrad

n_gazatova@mail.ruhttps://orcid.org/0000-0002-4543-7850БограяМ. М.BograyaM. M.

Бограя Мария Михайловна - инженер Центра иммунологии и клеточных биотехнологий

г. Калининград

Bograya Maria M. - engineer at Center for Immunology and Cellular Biotechnology

 Kaliningrad

mbograya@mail.ruhttps://orcid.org/0000-0002-0732-8717НаумоваЕ. Л.NaumovaE. L.

Наумова Елена Леонидовна - к.м.н., доцент кафедры терапии

г. Томск

Naumova Elena L. - PhD (Med.), assistant professor at Dept of General Medical Practice and Outpatient Therapy

Tomsk

naumova-elena@yandex.ruhttps://orcid.org/0009-0005-0536-238XДолгалеваМ. И.DolgalevaM. I.

Долгалева Мария Игоревна - зам. главного врача по онкологии; главный внештатный специалист-онколог Калининградской области

г. Калининград

Dolgaleva Maria I. - deputy chief physician on oncology; chief external specialist oncologist of the Kaliningrad region

Kaliningrad

Fatael2739@gmail.comФГАОУ ВО «Балтийский федеральный университет имени Иммануила Канта»РоссияImmanuel Kant Baltic Federal UniversityRussian FederationФГБОУ ВО «Ярославский государственный медицинский университет»РоссияYaroslavl State Medical UniversityRussian FederationФГБОУ ВО «Сибирский Государственный Медицинский Университет»РоссияSiberian State Medical UniversityRussian FederationГБУЗ КО «Областная клиническая больница»РоссияRegional Clinical HospitalRussian Federation20241005202407«Диагностика и онкотерапия» (1)5559Copyright © Тихонова О.А., Дружинин Д.С., Литвинова Л.С., Докторова С.А., Тодосенко Н.М., Газатова Н.Д., Бограя М.М., Наумова Е.Л., Долгалева М.И., 20242024Тихонова О.А., Дружинин Д.С., Литвинова Л.С., Докторова С.А., Тодосенко Н.М., Газатова Н.Д., Бограя М.М., Наумова Е.Л., Долгалева М.И.Tikhonova O.A., Druzhinin D.S., Litvinova L.S., Doktorova S.A., Todosenko N.M., Gazatova N.D., Bograya M.M., Naumova E.L., Dolgaleva M.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3689

В последнее время активно обсуждается роль дисбаланса витаминов в канцерогенезе. Исследования, направленные на оценку их роли в процессах развития рака различны, а оценка исходного уровня витаминов актуальна при планировании противоопухолевой терапии.

Цель исследования

Цель исследования. Определить состояние исходного уровня витаминов группы В и гомоцистеина перед проведением химиотерапии у пациентов разного онкологического профиля.

Материалы и методы исследования. Определён уровень витаминов В1, В6, В9, активной формы В12* и гомоцистеина всвежезамороженной плазме методом иммуноферментного анализа (ИФА) с использованием тест-систем у 66 пациентов с верифицированными злокачественными новообразованиями ЗНО) до химиотерапии. В исследование включено 66 пациентов: женщины n=40 и мужчин n=26, с ЗНО: раком желудка n=12, колоректальным раком n=21, раком легких n=11, раком органов малого таза n=22.

Результаты исследования

Результаты исследования. По результатам исследования повышение уровня холотранскобаламина (Холо-ТК) и снижение гомоцистеина в сравнении с референтными значениями наблюдалось в 100% случаев. Значимое различие обнаружено только для В1: достоверные различия между пациентами с колоректальным раком и с раком малого таза (у последних среднее значение уровней В1 было выше в 2.4 раза при p = 0.0425). По результатам корреляционного анализы определена слабая связь между В12 и В9. При сравнении уровня витамина В12 и гомоцистеина у пациентов после оперативного лечения и без него не было выявлено достоверных различий.

Заключение

Заключение. Повышение уровня Холо-ТК и снижение уровня гомоцистеина методом ИФА характерно для всех разновидностей солидного рака, не зависит от пола, возраста, стадии и предшествующего оперативного вмешательства. Относительное снижение витамина В1 характерно для колоректального рака.

Recently, the role of vitamin imbalance in carcinogenesis has been actively discussed. Studies aimed at assessing their role in the processes of cancer development are various, and the evaluation of the initial level of vitamins is relevant when planning antitumor therapy.

Objective

Objective. To determine the state of the initial level of B vitamins and homocysteine before chemotherapy in patients of different oncologic profile.

Material sand Methods

Material sand Methods. The level of vitamins B1, B6, B9, active form of B12* and homocysteine in fresh frozen plasma was determined by enzyme[1]linked immunosorbent assay (ELISA) using test systems in 66 patients with verified malignant neoplasms before chemotherapy. The study included 66 patients: women n=40 and men n=26, with cancer: gastric n=12, colorectal cancer n=21, cancer lung n=11, cancer pelvic organs n=22.

Results

Results. According to the results of the study the increase in the level of holotranscobalamin (Holo-TC) and decrease in homocysteine in comparison with reference values was observed in 100% of cases. Significant difference was found only for B1: reliable differences between patients with colorectal cancer and with pelvic cancer (in the latter the mean value of B1 levels was 2.4 times higher at p = 0.0425). According to the results of correlation analysis, a weak correlation between B12 and B9 was determined. When comparing the levels of vitamin B12 and homocysteine in patients after surgical treatment and without it, no significant differences were found.

Conclusion

Conclusion. Increased Holo-TC levels and decreased homocysteine levels by ELISA are characteristic of all varieties of solid cancer, independent of sex, age, stage and previous surgical intervention. A relative decrease in vitamin B1 is characteristic of colorectal cancer

ракбиомаркерыВ1(тиамин)В6(пиридоксин)В9 (фолиевая кислота)В12 (холотранскобаламин)гомоцистеинcancerbiomarkersB1(thiamine)B6 (pyridoxine)B9 (folic acid)active vitamin B12(holotranscobalamin)homocysteineДанное исследование было поддержано из средств программы стратегического академического лидерства «Приоритет 2030» БФУ им. И. Канта No 314-Л‑22This research was supported by the strategic academic leadership program «Priority 2030» Immanuel Kant Baltic Federal University No. 314-L‑22ReferencesPeterson CT, Rodionov DA, Osterman AL, Peterson SN. B Vitamins and Their Role in Immune Regulation and Cancer. Nutrients. 2020;12(11). doi: 10.3390/nu12113380. PMID: 33158037.Peterson CT, Rodionov DA, Osterman AL, Peterson SN. B Vitamins and Their Role in Immune Regulation and Cancer. Nutrients. 2020;12(11). doi: 10.3390/nu12113380. PMID: 33158037.Zastre JA, Sweet RL, Hanberry BS, Ye S. Linking.Vitamin B1 with cancer cell metabolism. Cancer Metab. 2013;1(1):16. doi: 10.1186/2049–3002–1–16. PMID: 24280319.Zastre JA, Sweet RL, Hanberry BS, Ye S. Linking.Vitamin B1 with cancer cell metabolism. Cancer Metab. 2013;1(1):16. doi: 10.1186/2049–3002–1–16. PMID: 24280319.Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B 12 is strongly associated with solid cancer. Sci Rep. 2021;11(1):13361. doi: 10.1038/s41598–021–92945-y. PMID: 34172805.Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B 12 is strongly associated with solid cancer. Sci Rep. 2021;11(1):13361. doi: 10.1038/s41598–021–92945-y. PMID: 34172805.Liu S, Miriyala S, Keaton MA, et al. Metabolic effects of acute thiamine depletion are reversed by rapamycin in breast and leukemia cells. PLoS One. 2014;9(1): e85702. doi: 10.1371/journal.pone.0085702. PMID: 24454921.Liu S, Miriyala S, Keaton MA, et al. Metabolic effects of acute thiamine depletion are reversed by rapamycin in breast and leukemia cells. PLoS One. 2014;9(1): e85702. doi: 10.1371/journal.pone.0085702. PMID: 24454921.Bruce WR, Furrer R, Shangari N, et al. Marginal dietary thiamin deficiency induces the formation of colonic aberrant crypt foci (ACF) in rats. Cancer Lett. 2003;202(2):125–9. doi: 10.1016/j.canlet.2003.08.005. PMID: 14643441.Bruce WR, Furrer R, Shangari N, et al. Marginal dietary thiamin deficiency induces the formation of colonic aberrant crypt foci (ACF) in rats. Cancer Lett. 2003;202(2):125–9. doi: 10.1016/j.canlet.2003.08.005. PMID: 14643441.Trebukhina RV, Ostrovsky YM, Shapot VS, et al. Turnover of thiamin and activities of thiamin pyrophosphate-dependent enzymes in tissues of mice with Ehrlich ascites carcinoma. Nutr Cancer. 1984;6(4):260–73. doi: 10.1080/01635588509513832. PMID: 6545581.Trebukhina RV, Ostrovsky YM, Shapot VS, et al. Turnover of thiamin and activities of thiamin pyrophosphate-dependent enzymes in tissues of mice with Ehrlich ascites carcinoma. Nutr Cancer. 1984;6(4):260–73. doi: 10.1080/01635588509513832. PMID: 6545581.Baker H, Frank O, Chen T, et al. Elevated vitamin levels in colon adenocarcinoma as compared with metastatic liver adenocarcinoma from colon primary and normal adjacent tissue. Cancer. 1981;47(12):2883–6. doi: 10.1002/1097–0142(19810615)47:12<2883. PMID: 7260874.Baker H, Frank O, Chen T, et al. Elevated vitamin levels in colon adenocarcinoma as compared with metastatic liver adenocarcinoma from colon primary and normal adjacent tissue. Cancer. 1981;47(12):2883–6. doi: 10.1002/1097–0142(19810615)47:12<2883. PMID: 7260874.Obeid R. High Plasma Vitamin B 12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations. Nutrients. 2022;14(21). doi: 10.3390/nu14214476. PMID: 36364737.Obeid R. High Plasma Vitamin B 12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations. Nutrients. 2022;14(21). doi: 10.3390/nu14214476. PMID: 36364737.Zulfiqar AA, Andres E, Lorenzo Villalba N. Hypervitaminosis B 12. Our experience and a review. Medicina (B Aires). 2019;79(5):391–6. PMID: 31671389.Zulfiqar AA, Andres E, Lorenzo Villalba N. Hypervitaminosis B 12. Our experience and a review. Medicina (B Aires). 2019;79(5):391–6. PMID: 31671389.Fanidi A, Carreras-Torres R, Larose TL et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019;145(6):1499–503. doi: 10.1002/ijc.32033. PMID: 30499135.Fanidi A, Carreras-Torres R, Larose TL et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019;145(6):1499–503. doi: 10.1002/ijc.32033. PMID: 30499135.Boughanem H, Hernandez-Alonso P, Tinahones A et al. Association between Serum Vitamin B 12 and Global DNA Methylation in Colorectal Cancer Patients. Nutrients. 2020;12(11). doi: 10.3390/nu12113567.PMID: 33233812.Boughanem H, Hernandez-Alonso P, Tinahones A et al. Association between Serum Vitamin B 12 and Global DNA Methylation in Colorectal Cancer Patients. Nutrients. 2020;12(11). doi: 10.3390/nu12113567.PMID: 33233812.Hasan T, Arora R, Bansal AK, et al. Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med. 2019;51(2):1–13. doi: 10.1038/s12276–019–0216–4. PMID: 30804341.Hasan T, Arora R, Bansal AK, et al. Disturbed homocysteine metabolism is associated with cancer. Exp Mol Med. 2019;51(2):1–13. doi: 10.1038/s12276–019–0216–4. PMID: 30804341.Sun CF, Haven TR, Wu TL, et al. Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. Clin Chim Acta. 2002;321(1–2):55–62. doi: 10.1016/s0009–8981(02)00092-x. PMID: 12031593.Sun CF, Haven TR, Wu TL, et al. Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker. Clin Chim Acta. 2002;321(1–2):55–62. doi: 10.1016/s0009–8981(02)00092-x. PMID: 12031593.Arendt JF, Pedersen L, Nexo E, Sorensen HT. Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study. J Natl Cancer Inst. 2013;105(23):1799–805. doi: 10.1093/jnci/djt315. PMID: 24249744.Arendt JF, Pedersen L, Nexo E, Sorensen HT. Elevated plasma vitamin B12 levels as a marker for cancer: a population-based cohort study. J Natl Cancer Inst. 2013;105(23):1799–805. doi: 10.1093/jnci/djt315. PMID: 24249744.Urbanski G, Hamel JF, Prouveur B, et al. Strength of the Association of Elevated Vitamin B 12 and Solid Cancers: An Adjusted Case-Control Study. J Clin Med. 2020;9(2). doi: 10.3390/jcm9020474. PMID: 32050436.Urbanski G, Hamel JF, Prouveur B, et al. Strength of the Association of Elevated Vitamin B 12 and Solid Cancers: An Adjusted Case-Control Study. J Clin Med. 2020;9(2). doi: 10.3390/jcm9020474. PMID: 32050436.Devalia V, Hamilton MS, Molloy AM, British Committee for Standards in H. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496–513. doi: 10.1111/bjh.12959. PMID: 24942828.Devalia V, Hamilton MS, Molloy AM, British Committee for Standards in H. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496–513. doi: 10.1111/bjh.12959. PMID: 24942828.Hannibal L, Lysne V, Bjorke-Monsen AL, et al. Biomarkers and Algorithms for the Diagnosis of Vitamin B 12 Deficiency. Front Mol Biosci. 2016;3:27. doi: 10.3389/fmolb.2016.00027. PMID: 27446930.Hannibal L, Lysne V, Bjorke-Monsen AL, et al. Biomarkers and Algorithms for the Diagnosis of Vitamin B 12 Deficiency. Front Mol Biosci. 2016;3:27. doi: 10.3389/fmolb.2016.00027. PMID: 27446930.Valente E, Scott JM, Ueland PM, et al. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B(1)(2) status in the elderly. Clin Chem. 2011;57(6):856–63. doi: 10.1373/clinchem.2010.158154 PMID: 21482749.Valente E, Scott JM, Ueland PM, et al. Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B(1)(2) status in the elderly. Clin Chem. 2011;57(6):856–63. doi: 10.1373/clinchem.2010.158154 PMID: 21482749.Sysel AM, Valli VE, Nagle RB, Bauer JA. Immunohistochemical quantification of the vitamin B 12 transport protein (TCII), cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts. Anticancer Res. 2013;33(10):4203–12. PMID: 24122983.Sysel AM, Valli VE, Nagle RB, Bauer JA. Immunohistochemical quantification of the vitamin B 12 transport protein (TCII), cell surface receptor (TCII-R) and Ki-67 in human tumor xenografts. Anticancer Res. 2013;33(10):4203–12. PMID: 24122983.Lacombe V, Lenaers G, Urbanski G. Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers. Nutrients. 2022;14(10). doi: 10.3390/nu14102058. PMID: 35631199.Lacombe V, Lenaers G, Urbanski G. Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers. Nutrients. 2022;14(10). doi: 10.3390/nu14102058. PMID: 35631199.Andres E, Loukili NH, Noel E, et al. Vitamin B 12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251–9. doi: 10.1503/cmaj.1031155. PMID: 15289425.Andres E, Loukili NH, Noel E, et al. Vitamin B 12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251–9. doi: 10.1503/cmaj.1031155. PMID: 15289425.Lacombe V, Patsouris A, Delattre E, Lacout C, Urbanski G. Evolution of plasma vitamin B(12) in patients with solid cancers during curative versus supportive care. Arch Med Sci. 2021;17(6):1811–5.doi: 10.5114/aoms/140974. PMID: 34900064.Lacombe V, Patsouris A, Delattre E, Lacout C, Urbanski G. Evolution of plasma vitamin B(12) in patients with solid cancers during curative versus supportive care. Arch Med Sci. 2021;17(6):1811–5.doi: 10.5114/aoms/140974. PMID: 34900064.Hu Y, Kim HI, Hyung WJ, et al. Vitamin B(12) deficiency after gastrectomy for gastric cancer: an analysis of clinical patterns and risk factors. Ann Surg. 2013;258(6):970–5. doi: 10.1097/SLA.0000000000000214. PMID: 24096753.Hu Y, Kim HI, Hyung WJ, et al. Vitamin B(12) deficiency after gastrectomy for gastric cancer: an analysis of clinical patterns and risk factors. Ann Surg. 2013;258(6):970–5. doi: 10.1097/SLA.0000000000000214. PMID: 24096753.Newman AC, Maddocks ODK. One-carbon metabolism in cancer. Br J Cancer. 2017;116(12):1499–504. doi: 10.1038/bjc.2017.118. PMID: 28472819.Newman AC, Maddocks ODK. One-carbon metabolism in cancer. Br J Cancer. 2017;116(12):1499–504. doi: 10.1038/bjc.2017.118. PMID: 28472819.

The authors declare that there are no conflicts of interest present.