Свободно-циркулирующие нуклеиновые кислоты как диагностический биомаркер онкологических заболеваний

Авторы

  • O. V. Bulgakova Евразийский национальный университет им. Л.Н. Гумилева, Казахстан, г. Астана
  • A. Zh. Kausbekova Евразийский национальный университет имени Л.Н. Гумилева, Казахстан, г. Астана
  • R. I. Bersimbaev Евразийский национальный университет имени Л.Н. Гумилева, Казахстан, г. Астана

DOI:

https://doi.org/10.26577/eb-2018-1-1316
        143 187

Аннотация

В последнее десятилетие одним из актуальных вопросов современной науки является поиск биомаркеров, которые обладали бы высокой чувствительностью и специфичностью для неинвазивной диагностики онкологических заболеваний. Иммунологические методы диагностики злокачественных опухолей в целом находят пока очень скромное клиническое применение по причине низкой специфичности используемых на данный момент опухолевых маркеров.

Исследование свободно - циркулирующих нуклеиновых кислот в плазме и сыворотке крови у больных с онкопатологией представляет перспективное направление современной молекулярной диагностики.

Свободно - циркулирующие нуклеиновые кислоты включают ДНК, РНК, микроРНК, вирусную ДНК/РНК и митохондриальную ДНК. При этом свободно-циркулирующие нуклеиновые кислоты могут присутствовать как в свободной форме, так и в составе надмолекулярных нуклеопротеиновых комплексов.

Однако, многие аспекты, связанные с биогензом свободно-циркулирующих нуклеиновых кислот, а также их роль в механизме развития злокачественных опухолей до сих пор остаются не ясными.

В этом обзоре основное внимание уделяется биологическим свойствам свободно-циркулирующих нуклеиновых кислот, биогенезу, их роли в патогенезе злокачественных новообразований и возможности применения сцНК в качестве биомаркеров в диагностике онкологических заболеваний.

Ключевые слова: свободно - циркулирующие нуклеиновые кислоты, свободно-циркулирующая ДНК, микроРНК, митохондриальная ДНК, рак, биомаркеры.

Библиографические ссылки

1 Abolhassani M., Tillotson J., Chiao J. Characterization of the release of DNA by a human leukemia-cell line HL-60 // International Journal of Oncology. – 1994. – Vol. 4. – No. 2. – P.417–421.
2 Bettegowda C., Sausen M., Leary R.J., Kinde I., Wang Y., Agrawal N., Diaz L.A. Detection of Circulating Tumor DNA in Earlyand Late-Stage Human Malignancies // Science Translational Medicine. – 2014. – Vol. 6(224). –P.224ra24–224ra24.
3 Bersimbaev R.I., Bulgakova O.V. Residential radon exposure and lung cancer risk in Kazakhstan // Radon: InTech, London. In: F. Adrovic editors. - 2017. — Р.93—124.
4 Bersimbaev R. I., Bulgakova O. The health effects of radon and uranium on the population of Kazakhstan // Genes and Environment. - 2015.-Vol.37. – Р. 1-10.
5 Borghini A., Mercuri A., Turchi S., Chiesa M.R., Piccaluga E., Andreassi M.G. Increased circulating cell-free DNA levels and mtDNA fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation // Environ. Mol. Mutagen. – 2015. – Vol. 56(3). – P.293-300.
6 Budnik L.T., Kloth S., Baur X., Preisser A.M., Schwarzenbach H. Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides // PloS. One. - 2013. – Vol. 8(5). – P.e64413.
7 El-Hefnawy T., Raja S., Kelly L., Bigbee W.L., Kirkwood J.M., Luketich J.D. and Godfrey T.E. Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics // Clin. Chem. - 2004. – Vol.50. – P.564-573.
8 Erpenbeck L., Schön M.P. Neutrophil extracellular traps: protagonists of cancer progression? // Oncogene. - 2017. – Vol. 4:36(18). - P.2483-2490.
9 Gahan P.B., Stroun M. The biology of circulating nucleic acids in plasma and serum (CNAPS) / Kikuchi Y., Rykova E. etc. // Extracellular nucleic acids.- NY, Springer, 2010. - P. 168-183.
10 Galanopoulos M., Tsoukalas N., Papanikolaou I. S., Tolia M., Gazouli M., & Mantzaris G. J. Abnormal DNA methylation as a cell-free circulating DNA biomarker for colorectal cancer detection: A review of literature // World Journal of Gastrointestinal Oncology. - 2017.- Vol.9(4). - P.142–152.
11 Geretto M., Pulliero A., Rosano C., Zhabayeva D., Bersimbaev R., Izzotti A. Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators // American Journal of Cancer Research. - 2017. - Vol.7(6). – P.1350–1371.
12 Gezer U., Holdenrieder S. Post-translational histone modifications in circulating nucleosomes as new biomarkers in colorectal cancer // In Vivo (Athens, Greece). – 2014. - Vol. - 28(3). – P.287–292
13 Hendriks R.J., Dijkstra S., Smit F.P., Vandersmissen J., Van de Voorde H., Mulders P.F.A., van Oort I.M., Van Criekinge W., Schalken J.A. Epigenetic markers in circulating cell-free DNA as prognostic markers for survival of castration-resistant prostate cancer patients // Prostate. – 2018. – Vol. 78(5). – P.336-342.
14 Izzotti A., Carozzo S., Pulliero A., Zhabayeva D., Ravetti J.L., Bersimbaev R. Extracellular MicroRNA in liquid biopsy: applicability in cancer diagnosis and prevention // American journal of cancer research. – 2016. – Vol. 6. – No.7. – P.1461-1493.
15 Jiang W.W., Masayesva B., Zahurak M., Carvalho A.L., Rosenbaum E., Mambo E., Zhou S., Minhas K., Benoit N., Westra W.H., Alberg A., Sidransky D., Koch W., Califano J. Increased mitochondrial DNA content in saliva associated with head and neck cancer // Clin. Cancer Res. - 2005. – Vol. 11. – P.2486–2491.
16 Lu H., Busch J., Jung M., Rabenhorst S., Ralla B., Kilic E., Jung K. Diagnostic and prognostic potential of circulating cell-free genomic and mitochondrial DNA fragments in clear cell renal cell carcinoma patients // Clinica Chimica. Acta. - 2016. – Vol. 452. – P.109–119.
17 Li L., Hann H.-W., Wan S., Hann R. S., Wang C., Lai Y., Ye X., Evans A., Myers R.E., Ye Z., Li B., Xing J.,Yang H. Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection // Scientific Reports. - 2016. – Vol. 6. – P.23992.
18 Leon S.A., Shapiro B., Sklaroff D.M., Yaros M.J. Free DNA in the serum of cancer patients and the effect of therapy // Cancer Res. – 1977. – Vol. 37. - P. 646–650.
19 Lee R.C., Feinbaum R.L., Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 // Cell. – 1993. –Vol. 75. – P. 843-854.
20 Lehmann-Werman R., Neiman D., Zemmour H., Moss J., Magenheim J., Vaknin-Dembinsky A., Dor Y. Identification of tissue-specific cell death using methylation patterns of circulating DNA //Proc. Natl. Acad. Sci. USA. - 2016. - Vol.113(13). – P.1826-1834.
21 Mahmoud E.H., Fawzy A., Ahmad O.K., Ali A.M. Plasma Circulating Cell-free Nuclear and Mitochondrial DNA as Potential Biomarkers in the Peripheral Blood of Breast Cancer Patients // Asian Pac. J. Cancer. Prev. – 2015. - Vol. 16(18). – P.8299-305.
22 Marsman G., Zeerleder S., Luken B.M. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation // Cell Death & Disease. - 2016. – Vol. 7. – No. 12. P. :e2518
23 Mehra N., Penning M., Maas J., van Daal N., Giles R.H., Voest E.E. Circulating mitochondrial nucleic acids have prognostic value for survival in patients with advanced prostate cancer // Clin. Cancer Res. – 2007. – Vol. 13. – P.421–426.
24 Murtaza M., Dawson S-J., Tsui D.W.Y., Gale D., Forshew T., Piskorz A.M., Rosenfeld N. Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA // Nature. - 2013. – Vol. 497(7447). – P.108–112.
25 Nakahira K., Hisata S., Choi A.M.K. The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases // Antioxidants & Redox Signaling. - 2015. – Vol. 23(17). – P. 1329–1350.
26 Petrovic N., Ergun S. miRNAs as Potential Treatment Targets and Treatment Options in Cancer // Mol. Diagn. Ther. - 2018. DOI: 10.1007/s40291-017-0314-8
27 Pelosi G., Schianchi E., Dell'orto P., Veronesi G., Spaggiari L., Pasini F., Sozzi G., Brambilla E., Griso C., Viale G. Detecting cell-free circulating hTERT mRNA in the plasma may identify a subset of nonsmall cell lung cancer patients // Virchows Arch. – 2006. – Vol. 448. - No. 1. – P.7-15.
28 Sansone P., Savini C., Kurelac I., Chang Q., Amato L. B., Strillacci A., Bromberg J. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer // Proceedings of the National Academy of Sciences of the United States of America. - 2017. – Vol. 114(43). - P.E9066–E9075.
29 Sorenson G.D., Pribish D.M., Valone F.H., Memoli V.A., Bzik D.J., Yao S. Soluble normal and mutated DNA sequences from single-copy genes in human blood // Cancer Epidemiol. Biomarkers Prev. - 1994. – Vol. 3. – P.67–71.
30 Stroun M., Anker P., Lyautey J., Lederrey C., Maurice P.A. Isolation and characterization of DNA from the plasma of cancer patients // European Journal of Cancer & Clinical Oncology. – 1987. – Vol. 23. – No.6 . – P. 707–712
31 Sudakov N.P., Apartsin K.A., Lepekhova S.A., Nikiforov S.B., Katyshev A. Lifshits G. I., Lifshits G.I., Vybivantseva A.V., Konstantinov Y.M. The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome // European Journal of Medical Research. – 2017. - Vol. 22. - P. 1-6.
32 Snyder M.W., Kircher M., Hill A.J., Daza R.M., Shendure J. Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin // Cell. - 2016. - Vol. 164(1–2). –P.57–68.
33 Vasioukhin V., Anker P., Maurice P., Lyautey J., Lederrey C., Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia // Br. J. Haematol. – 1994. –Vol. 86. - P.774– 779.
34 Weerasinghe P., Buja L.M. Oncosis: an important non-apoptotic mode of cell death // Experimental and Molecular Pathology. – 2012. – Vol. 93(3). – P.302–308.
35 Wong B.C., Chan K.C., Chan A.T., Leung S.F., Chan L.Y., Chow K.C. and Lo Y.M. Reduced plasma RNA integrity in nasopharyngeal carcinoma patients // Clin. Cancer. Res. – 2006. – Vol. 12. – P. 2512-2516.
36 Xing J., Chen M., Wood C.G., Lin J., Spitz M.R., Ma J., Amos C.I., Shields P.G., Benowitz N.L., Gu J., de Andrade M., Swan G.E., Wu X. Mitochondrial DNA content: Its genetic heritability and association with renal cell carcinoma // J. Natl. Cancer Inst. – 2008. – Vol. 100. – P.1104–1112.
37 Yu M. Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges // Mitochondrial DNA. – 2012. – Vol.23. – No.5. – P.329–332.
38 Zhang Q., Itagaki K., and Hauser C.J. Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase // Shock.- 2010. – Vol. 34. – P.55–59.
39 Тамкович С.Н., Власов В.В., Лактионов П.П. Циркулирующие ДНК крови и их использование в медицинской диагностике //Молекулярная биология. - 2008.- № 42(1). - С. 12-23.


Reference

1 Abolhassani M., Tillotson J., Chiao J. (1994) Characterization of the release of DNA by a human leukemia-cell line HL-60, International Journal of Oncology, vol.4, no 2, pp.417–421.
2 Bettegowda C., Sausen M., Leary R.J., Kinde I., Wang Y., Agrawal N., Diaz L.A. (2014) Detection of Circulating Tumor DNA in Earlyand Late-Stage Human Malignancies, Science Translational Medicine, vol. 6(224), pp.224ra24–224ra24.
3 Bersimbaev R.I., Bulgakova O.V. (2017) Residential radon exposure and lung cancer risk in Kazakhstan, Radon: InTech, London. In: F. Adrovic editors, pp.93—124.
4 Bersimbaev R. I., Bulgakova O. (2015) The health effects of radon and uranium on the population of Kazakhstan, Genes and Environment, vol.37, pp. 1-10.
5 Borghini A., Mercuri A., Turchi S., Chiesa M.R., Piccaluga E., Andreassi M.G. (2015) Increased circulating cell-free DNA levels and mtDNA fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation, Environ. Mol. Mutagen.,vol. 56(3), pp.293-300.
6 Budnik L.T., Kloth S., Baur X., Preisser A.M., Schwarzenbach H. (2013) Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides, PloS. One., vol. 8(5), pp.e64413.
7 El-Hefnawy T., Raja S., Kelly L., Bigbee W.L., Kirkwood J.M., Luketich J.D. and Godfrey T.E. (2004) Characterization of amplifiable, circulating RNA in plasma and its potential as a tool for cancer diagnostics, Clin. Chem., vol.50, pp.564-573.
8 Erpenbeck L., Schön M.P. (2017) Neutrophil extracellular traps: protagonists of cancer progression? Oncogene, vol. 4:36(18), pp.2483-2490.
9 Gahan P.B., Stroun M. (2010) The biology of circulating nucleic acids in plasma and serum (CNAPS), Extracellular nucleic acids, NY, Springer, Kikuchi Y., Rykova E. etc., pp. 168-183.
10 Galanopoulos M., Tsoukalas N., Papanikolaou I. S., Tolia M., Gazouli M., & Mantzaris G. J. (2017) Abnormal DNA methylation as a cell-free circulating DNA biomarker for colorectal cancer detection: A review of literature, World Journal of Gastrointestinal Oncology, vol.9(4), pp.142–152.
11 Geretto M., Pulliero A., Rosano C., Zhabayeva D., Bersimbaev R., Izzotti A. (2017) Resistance to cancer chemotherapeutic drugs is determined by pivotal microRNA regulators, American Journal of Cancer Research,vol.7(6), pp.1350–1371.
12 Gezer U., Holdenrieder S. (2014) Post-translational histone modifications in circulating nucleosomes as new biomarkers in colorectal cancer, In Vivo (Athens, Greece), vol. 28(3), pp.287–292
13 Hendriks R.J., Dijkstra S., Smit F.P., Vandersmissen J., Van de Voorde H., Mulders P.F.A., van Oort I.M., Van Criekinge W., Schalken J.A. (2018) Epigenetic markers in circulating cell-free DNA as prognostic markers for survival of castration-resistant prostate cancer patients, Prostate, vol. 78(5), pp.336-342.
14 Izzotti A., Carozzo S., Pulliero A., Zhabayeva D., Ravetti J.L., Bersimbaev R. (2016) Extracellular MicroRNA in liquid biopsy: applicability in cancer diagnosis and prevention, American journal of cancer research, vol. 6,no 7, pp.1461-1493.
15 Jiang W.W., Masayesva B., Zahurak M., Carvalho A.L., Rosenbaum E., Mambo E., Zhou S., Minhas K., Benoit N., Westra W.H., Alberg A., Sidransky D., Koch W., Califano J. (2005) Increased mitochondrial DNA content in saliva associated with head and neck cancer, Clin. Cancer Res., vol. 11, pp.2486–2491.
16 Lu H., Busch J., Jung M., Rabenhorst S., Ralla B., Kilic E., Jung K. (2016) Diagnostic and prognostic potential of circulating cell-free genomic and mitochondrial DNA fragments in clear cell renal cell carcinoma patients, Clinica Chimica. Acta., vol. 452, pp.109–119.
17 Li L., Hann H.-W., Wan S., Hann R. S., Wang C., Lai Y., Ye X., Evans A., Myers R.E., Ye Z., Li B., Xing J.,Yang H. (2016) Cell-free circulating mitochondrial DNA content and risk of hepatocellular carcinoma in patients with chronic HBV infection, Scientific Reports, vol. 6, pp.23992.
18 Leon S.A., Shapiro B., Sklaroff D.M., Yaros M.J. (1977) Free DNA in the serum of cancer patients and the effect of therapy, Cancer Res., vol. 37, pp. 646–650.
19 Lee R.C., Feinbaum R.L., Ambros V. (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14, Cell, vol. 75, pp. 843-854.
20 Lehmann-Werman R., Neiman D., Zemmour H., Moss J., Magenheim J., Vaknin-Dembinsky A., Dor Y. (2016) Identification of tissue-specific cell death using methylation patterns of circulating DNA, Proc. Natl. Acad. Sci. USA., vol.113(13), pp.1826-1834.
21 Mahmoud E.H., Fawzy A., Ahmad O.K., Ali A.M. (2015) Plasma Circulating Cell-free Nuclear and Mitochondrial DNA as Potential Biomarkers in the Peripheral Blood of Breast Cancer Patients, Asian Pac. J. Cancer. Prev., vol. 16(18), pp.8299-305.
22 Marsman G., Zeerleder S., Luken B.M. (2016) Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation, Cell Death & Disease, vol. 7, no 12, pp.e2518
23 Mehra N., Penning M., Maas J., van Daal N., Giles R.H., Voest E.E. (2007) Circulating mitochondrial nucleic acids have prognostic value for survival in patients with advanced prostate cancer, Clin. Cancer Res., vol. 13, pp.421–426.
24 Murtaza M., Dawson S-J., Tsui D.W.Y., Gale D., Forshew T., Piskorz A.M., Rosenfeld N. (2013) Non-invasive analysis of acquired resistance to cancer therapy by sequencing of plasma DNA, Nature, vol. 497(7447), pp.108–112.
25 Nakahira K., Hisata S., Choi A.M.K. (2015) The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases, Antioxidants & Redox Signaling, vol. 23(17), pp. 1329–1350.
26 Petrovic N., Ergun S. (2018) miRNAs as Potential Treatment Targets and Treatment Options in Cancer, Mol. Diagn. Ther., DOI: 10.1007/s40291-017-0314-8.
27 Pelosi G., Schianchi E., Dell'orto P., Veronesi G., Spaggiari L., Pasini F., Sozzi G., Brambilla E., Griso C., Viale G. (2006) Detecting cell-free circulating hTERT mRNA in the plasma may identify a subset of nonsmall cell lung cancer patients, Virchows Arch., vol. 448, no 1, pp.7-15.
28 Sansone P., Savini C., Kurelac I., Chang Q., Amato L. B., Strillacci A., Bromberg J. (2017) Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer, Proceedings of the National Academy of Sciences of the United States of America, vol. 114(43), pp.E9066–E9075.
29 Sorenson G.D., Pribish D.M., Valone F.H., Memoli V.A., Bzik D.J., Yao S. (1994) Soluble normal and mutated DNA sequences from single-copy genes in human blood, Cancer Epidemiol. Biomarkers Prev., vol. 3, pp.67–71.
30 Stroun M., Anker P., Lyautey J., Lederrey C., Maurice P.A. (1987) Isolation and characterization of DNA from the plasma of cancer patients, European Journal of Cancer & Clinical Oncology, vol. 23, no 6, pp. 707–712
31 Sudakov N.P., Apartsin K.A., Lepekhova S.A., Nikiforov S.B., Katyshev A. Lifshits G. I., Lifshits G.I., Vybivantseva A.V., Konstantinov Y.M. (2017) The level of free circulating mitochondrial DNA in blood as predictor of death in case of acute coronary syndrome, European Journal of Medical Research, vol. 22, pp. 1-6.
32 Snyder M.W., Kircher M., Hill A.J., Daza R.M., Shendure J. (2016) Cell-free DNA Comprises an In Vivo Nucleosome Footprint that Informs Its Tissues-Of-Origin,Cell, vol. 164(1–2), pp.57–68.
33 Tamkovich SN, Vlasov VV, Laktionov PP (2008) Cirkuliruyushchie DNK krovi i ih ispol'zovanie v medicinskoj diagnostike [Circulating blood DNA and their use in medical diagnostics], Molekulyarnaya biologiya, vol.42(1), pp.12-23.
34 Vasioukhin V., Anker P., Maurice P., Lyautey J., Lederrey C., Stroun M. (1994) Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia, Br. J. Haematol., vol. 86, pp.774– 779.
35 Weerasinghe P., Buja L.M. (2012) Oncosis: an important non-apoptotic mode of cell death, Experimental and Molecular Pathology, vol. 93(3), pp.302–308.
36 Wong B.C., Chan K.C., Chan A.T., Leung S.F., Chan L.Y., Chow K.C. and Lo Y.M. (2006) Reduced plasma RNA integrity in nasopharyngeal carcinoma patients, Clin. Cancer. Res., vol. 12, pp. 2512-2516.
37 Xing J., Chen M., Wood C.G., Lin J., Spitz M.R., Ma J., Amos C.I., Shields P.G., Benowitz N.L., Gu J., de Andrade M., Swan G.E., Wu X. (2008) Mitochondrial DNA content: Its genetic heritability and association with renal cell carcinoma, J. Natl. Cancer Inst., vol. 100, pp.1104–1112.
38 Yu M. (2012) Circulating cell-free mitochondrial DNA as a novel cancer biomarker: opportunities and challenges, Mitochondrial DNA, vol.23, no 5, pp.329–332.
39 Zhang Q., Itagaki K., and Hauser C.J. (2010) Mitochondrial DNA is released by shock and activates neutrophils via p38 map kinase, Shock., vol. 34, pp.55–59.

Загрузки

Как цитировать

Bulgakova, O. V., Kausbekova, A. Z., & Bersimbaev, R. I. (2018). Свободно-циркулирующие нуклеиновые кислоты как диагностический биомаркер онкологических заболеваний. Вестник КазНУ. Серия биологическая, 74(1), 62–73. https://doi.org/10.26577/eb-2018-1-1316

Выпуск

Раздел

МОЛЕКУЛЯРНАЯ БИОЛОГИЯ И ГЕНЕТИКА