Preview

Experimental and Clinical Gastroenterology

Advanced search

Diagnosis of early colorectal cancer using SHAP diagrams of combined models of electroviscoelastic parameters of erythrocytes and the level of fatty acids in their membranes

https://doi.org/10.31146/1682-8658-ecg-212-4-19-27

Abstract

The purpose of the work: to investigate the possibilities of combined models including electrical, viscoelastic parameters of erythrocytes, fatty acid levels of erythrocyte membranes, blood serum to improve the accuracy of early colorectal cancer (CRC) diagnosis. Materials and methods. 65 patients with stages 1-2 of CRC (mean age 63.3±9.6 years), 25 people with adenomatous polyps (AP) and 35 people of the comparison group were examined. The electrical and viscoelastic parameters of erythrocytes were studied by dielectrophoresis in the frequency range 5x104-106Hz; the levels of fatty acids (FA) in erythrocyte membranes, blood serum - using gas chromatography/mass spectrometry (Agilent 7000B (USA). When creating combined models, machine learning methods were used, for their interpretation and assessment of the degree of contribution of parameters to their composition, the method of constructing SHAP diagrams was used. Results. The use of combined models made it possible to achieve high diagnostic accuracy of distinction: for the pair “healthy versus patients with AP” during ROC analysis, the AUC was 1,0 (sensitivity 1,0, specificity 1,0). This model included parameters: diameter of erythrocytes at a frequency of 106Hz, proportion of deformed cells, summerized rigidity, amplitude of cell deformation at a frequency of 106Hz, speed of movement of erythrocytes to electrodes, electrical conductivity of cells, level of arachidonic acid, aggregation index at a frequency of 5x104Hz, polarizability at a frequency of 106Hz, total content of eicosapentaenoic and docosahexaenoic (n3), level of docosatetraenoic FA (n6). For the pair “healthy vs patients with 1-2 stages of CRC”, the AUC also reached 1,0 (an increase in AUC from 0.916 when using only FA to 1.0 in combined models) (sensitivity 1,0, specificity 1,0); the most significant for the distinction were: electrical conductivity, cell capacity, erythrocyte level of palmitooleiс C16:1;9 FA, the position of the crossover frequency, summerized rigidity, the amplitude of cell deformation at a frequency of 106 Hz, the degree of cell deformation at a frequency of 5x105 Hz, the level of the dipole moment, the total content of serum saturated FA, the proportion of deformed cells, serum levels myristic, palmitic FA, the rate of movement of erythrocytes to the electrodes, the level of docozapentaenoic C22:5n-3 in the blood serum. For the pair “patients with 1-2 stages of CRC versus patients with AP”, the AUC was 0,98 (sensitivity 0,92, specificity 1,0). This model consisted of indicators: the diameter of erythrocytes at different frequencies of the electric field, the level of decadienic FA (n6) in erythrocyte membranes, the proportion of discocytic forms, the content of stearic FA in erythrocytes, the serum level of palmitoleic C16:1;9 FA, the total content of saturated FA, aggregation indices at low frequencies of NUAEF, the level of pentadecanoic FA in erythrocyte membranes, serum stearic acid content and cell polarizability at a frequency of 106 Hz. Conclusion. The creation of combined models consisting of electrical, viscoelastic parameters of erythrocytes, fatty acid levels of erythrocyte membranes, blood serum using machine learning methods and the construction of SHAP diagrams ensures high accuracy in the diagnosis of precancerous and early colorectal cancer.

About the Authors

M. V. Kruchinina
Research Institute of Internal and Preventive Medicine- branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences; Novosibirsk State Medical University
Russian Federation


A. A. Gromov
Research Institute of Internal and Preventive Medicine- branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences
Russian Federation


M. V. Shashkov
Federal Research Center Boreskov Institute of Catalysis
Russian Federation


A. S. Sokolova
Novosibirsk Institute of Organic Chemistry SB RAS
Russian Federation


I. N. Yakovina
Novosibirsk State Technical University
Russian Federation


References

1. Siegel R. L., Miller K. D., Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590.

2. Siegel R. L., Fedewa S. A., Anderson W. F., et al. Colorectal cancer incidence patterns in the United States, 1974-2013. J Natl Cancer Inst. 2017;109(8): djw322. doi: 10.1093/jnci/djw322.

3. Cronin K. A., Lake A. J., Scott S., et al. Annual report to the nation on the status of cancer, part I: national cancer statistics. Cancer. 2018;124(13):2785-2800. doi: 10.1002/cncr.31551.

4. Araghi M., Soerjomataram I., Jenkins M., et al. Global trends in colorectal cancer mortality: projections to the year 2035.Int J Cancer. 2019;144(12):2992-3000. doi: 10.1002/ijc.32055.

5. Rex D. K., Boland C. R., Dominitz J. A., et al. Colorectal cancer screening: recommendations for physicians and patients from the U.S. multi-society task force on colorectal cancer. Gastroenterology. 2017;153(1):307-323. doi: 10.1053/j.gastro.2017.05.013.

6. US preventive services task force, Bibbins-Domingo K., Grossman D. C., Curry S. J., et al. Screening for colorectal cancer: US preventive services task force recommendation statement. JAMA. 2016;315(23):2564-2575. doi: 10.1001/jama.2016.5989.

7. Wolf A. M.D., Fontham E. T.H., Church T. R., et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018;68(4):250-281. doi: 10.3322/caac.21457.

8. Araghi M., Fidler M. M., Arnold M., et al. The future burden of colorectal cancer among US blacks and whites. J Natl Cancer Inst. 2018;110(7):791-793. doi: 10.1093/jnci/djx287.

9. Carethers J. M. Screening for colorectal cancer in African Americans: determinants and rationale for an earlier age to commence screening. Dig Dis Sci. 2015;60(3):711-21. doi: 10.1007/s10620-014-3443-5.

10. Sineshaw H. M., Ng K., Flanders W. D., et al. Factors that contribute to differences in survival of black vs white patients with colorectal cancer. Gastroenterology. 2018;154(4):906-915.e7. doi: 10.1053/j.gastro.2017.11.005.

11. Fedewa S. A., Flanders W. D., Ward K. C., et al. Racial and ethnic disparities in interval colorectal cancer incidence: a population-based cohort study. Ann Intern Med. 2017;166(12):857-866. doi: 10.7326/M16-1154.

12. Bresalier R. S., Grady W. M., Markowitz S. D., et al. Biomarkers for early detection of colorectal cancer: the early detection research network, a framework for clinical translation. Cancer Epidemiol Biomarkers Prev. 2020;29(12):2431-2440. doi: 10.1158/1055-9965.EPI-20-0234.

13. Prudnikova Ya.I., Kruchinina M. V., Gromov A. A., et al. Diagnostics of colorectal cancer: possibilities of pilot models based on electrical and viscoelastic characteristics red blood cells. Collection of materials of the section of young scientists of the Russian scientific and practical conference dedicated to the 40th anniversary of the Research Institute of Oncology of the Tomsk NIMC “Fundamental and clinical Oncology: achievements and prospects of development” edited by E. L. Choinzonov, N. V. Cherdyntseva, V. I. Chernov. Tomsk: Publishing House Vol. un-ta, 2019: 186-190. (in Russ.)@@ Прудникова Я. И., Кручинина М. В., Громов А. А., и соавт. Диагностика колоректального рака: возможности пилотных моделей на основе электрических и вязкоупругих характеристик эритроцитов. Сборник материалов секции молодых ученых Российской научно-практической конференции, посвященной 40-летию НИИ онкологии Томского НИМЦ «Фундаментальная и клиническая онкология: достижения и перспективы развития» под ред. Е. Л. Чойнзонова, Н. В. Чердынцевой, В. И. Чернова. Томск: Изд-во Том. ун-та, 2019: 186-190.

14. Kruchinina M. V., Prudnikova Ya. I., Gromov A. A., et al. New opportunities for colorectal cancer diagnostics using an optical cell detection system based on dielectrophoresis. Optics and Spectroscopy. 2019; 126 (5): 652-657. (In Russ.) doi: 10.21883/0000000000.@@ Кручинина М. В., Прудникова Я. И., Громов А. А., и соавт. Новые возможности диагностики колоректального рака c помощью оптической системы детекции клеток на основе диэлектрофореза. Оптика и спектроскопия. 2019; 126 (5): 652-657. doi: 10.21883/0000000000.

15. Kruchinina M. V., Kruchinin V. N., Prudnikova Ya. I. et al. Study of the level of fatty acids in erythrocyte membranes and serum of patients with colorectal cancer in Novosibirsk. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology. 2018;5(2):50-61. (In Russ.) doi: 10.17650/2313-805X-2018-5-2-50-61.@@ Кручинина М. В., Кручинин В. Н., Прудникова Я. И., и соавт. Исследование уровня жирных кислот мембран эритроцитов и сыворотки крови у пациентов с колоректальным раком г. Новосибирска. Успехи молекулярной онкологии. 2018;5(2):50-61. doi: 10.17650/2313-805X-2018-5-2-50-61.

16. Kruchinina M. V., Osipenko M. F., Kruchinin V. N., et al. Feature of composition of fatty acids of erythrocyte membranes in patients with colorectal cancer of different stages. Experimental and Clinical Gastroenterology. 2018;(7):102-111. (In Russ.)@@ Кручинина М. В., Осипенко М. Ф., Кручинин В. Н., и соавт. Особенности состава жирных кислот мембран эритроцитов у пациентов с колоректальным раком различных стадий. Экспериментальная и клиническая гастроэнтерология. 2018;(7):102-111.

17. Kruchinina M. V., Kruchinin V. N., Gromov A. A., et al. Fatty acids of erythrocyte membranes and blood serum as biomarkers for early detection of colorectal cancer. Siberian journal of oncology. 2022;21(2):65-80. (In Russ.) doi: 10.21294/1814-4861-2022-21-2-65-80.@@ Кручинина М. В., Кручинин В. Н., Громов А. А., и соавт. Жирные кислоты мембран эритроцитов и сыворотки крови как биомаркеры для диагностики ранних стадий колоректального рака. Сибирский онкологический журнал. 2022;21(2):65-80. doi: 10.21294/1814-4861-2022-21-2-65-80.

18. Arab L., Akbar J. Biomarkers and the measurement of fatty acids. Public Health Nutr. 2002; 5: 865-871. doi: 10.1079/phn2002391

19. Kang J. X., Wang J. A simplified method for analysis of polyunsaturated fatty acids. BMC biochemistry. 2005; 6: 5-13. doi: 10.1186/1471-2091-6-5

20. Shashkov M. V., Sidelnikov V. N. Properties of columns with several pyridinium and imidazolium ionic liquid stationary phases. Journal of chromatography A. 2013; 1309: 56-63. doi: 10.1016/j.chroma.2013.08.030

21. Generalov V. M., Kruchinina M. V., Durymanov A. G., et al. Dielectrophoresis in the diagnosis of infectious and non-infectious diseases. Novosibirsk: Publishing house “CERIS”. 2011. 172 p. (In Russ.)@@ Генералов В. М., Кручинина М. В., Дурыманов А. Г., и соавт. Диэлектрофорез в диагностике инфекционных и неинфекционных заболеваний. Новосибирск: Изд-во «ЦЭРИС». 2011. 172 с.

22. Slack D., Hilgard S., Jia E., et al. Fooling lime and shap: adversarial attacks on post hoc explanation methods. AIES ‘20: Proceedings of the AAAI/ACM Conference on AI, Ethics, and Society. 2020: 180-186. doi: 10.1145/ 3375627.3375830.

23. Dielectrophoresis in biology and medicine: An educational and methodical manual / V. M. Generalov, M. V. Kruchinina, Gromov A. A., Shuvalov G. V. Novosibirsk: Publishing House of NSTU, 2017. 179 p. (In Russ.)@@ Диэлектрофорез в биологии и медицине: Учеб.-метод пособие / В. М. Генералов, М. В. Кручинина, Громов А. А., Шувалов Г. В. Новосибирск: Изд-во НГТУ, 2017. 179 с.

24. May-Wilson S., Sud A., Law P. J., et al. Pro-inflammatory fatty acid profile and colorectal cancer risk: A Mendelian randomisation analysis. European journal of cancer. 2017. 84: 228-238. doi: 10.1016/j.ejca.2017.07.034.

25. Michalak A., Mosinska P., Fichna J. Polyunsaturated fatty acids and their derivatives: therapeutic value for inflammatory, functional gastrointestinal disorders, and colorectal cancer. Frontiers in Pharmacology. 2016. 7: 459-467. doi: 10.3389/fphar.2016.00459.

26. Tae C. H., Kim S. E., Jung S. A., et al. Involvement of adiponectin in early stage of colorectal carcinogenesis. BMC cancer. 2014. 14: 811-819. doi: 10.1186/1471-2407-14-811.

27. Ohmori H., Fujii K., Kadochi Y., et al. Elaidic acid, a trans-fatty acid, enhances the metastasis of colorectal cancer cells. Pathobiology: journal of immunopathology, molecular and cellular biology. 2017. 84(3): 144-151. doi: 10.1159/000449205.

28. Coleman O. I., Lobner E. M., Bierwirth S., et al. Activated ATF6 induces intestinal dysbiosis and innate immune response to promote colorectal tumorigenesis. Gastroenterology. 2018;155(5):1539-1552.e12. doi: 10.1053/j.gastro.2018.07.028.

29. Li Y., Wu H., Xing C., et al. Prognostic evaluation of colorectal cancer using three new comprehensive indexes related to infection, anemia and coagulation derived from peripheral blood. J Cancer. 2020;11(13):3834-3845. doi: 10.7150/jca.42409.

30. Ghuman S., Van Hemelrijck M., Garmo H., et al. Serum inflammatory markers and colorectal cancer risk and survival. British journal of cancer. 2017. 116(10): 1358-1365. doi: 10.1038/bjc.2017.96.

31. Han S., Schroeder E. A., Silva-Garcia C.G., et al. Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. Nature. 2017. 544(7649): 185-190. doi: 10.1038/nature21686.

32. Shashkov M. V., Sidelnikov V. N. Properties of columns with several pyridinium and imidazolium ionic liquid stationary phases. Journal of chromatography A. 2013. 1309: 56-63. doi: 10.1016/j.chroma.2013.08.030.

33. Kang J. X., Wang J. A simplified method for analysis of polyunsaturated fatty acids. BMC biochemistry. 2005. 6: 5-13. doi: 10.1186/1471-2091-6-5.

34. Zhang P., Wen X., Gu F., et al. Role of serum polyunsaturated fatty acids in the development of colorectal cancer.Int J Clin Exp Med. 2015;8(9):15900-9.

35. Novitsky V. V., Ryazantseva N. V., Stepovaya E. A. Physiology and pathophysiology of erythrocyte. Tomsk: Tomsk Publishing House. un-ta, 2004. 202 p. (In Russ.)@@ Новицкий В. В., Рязанцева Н. В., Степовая Е. А. Физиология и патофизиология эритроцита. Томск: Изд-во Томск. ун-та, 2004. 202 c.

36. La Vecchia S, Sebastián C. Metabolic pathways regulating colorectal cancer initiation and progression. Semin Cell Dev Biol. 2020;98:63-70. doi: 10.1016/j.semcdb.2019.05.018.

37. Kruchinina M. V., Gromov A. A., Shcherbakova L. V., et al. Electric and viscoelastic parameters of erythrocytes in models for diagnostics of adenomatous polyps and stages of colorectal cancer in optical detection of cells in an inhomogeneous alternating electric field. Optics and Spectroscopy. 2021; 129(6): 684-697. (In Russ.) doi: 10.21883/OS.2021.06.50978.2-21.@@ Кручинина М. В., Громов А. А., Щербакова Л. В., и соавт. Электрические и вязкоупругие параметры эритроцитов в моделях для диагностики аденоматозных полипов и стадий колоректального рака при оптической детекции клеток в неоднородном переменном электрическом поле. Оптика и Спектроскопия. 2021; 129(6): 684-697. doi: 10.21883/OS.2021.06.50978.2-21.


Review

For citations:


Kruchinina M.V., Gromov A.A., Shashkov M.V., Sokolova A.S., Yakovina I.N. Diagnosis of early colorectal cancer using SHAP diagrams of combined models of electroviscoelastic parameters of erythrocytes and the level of fatty acids in their membranes. Experimental and Clinical Gastroenterology. 2023;(4):19-27. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-212-4-19-27

Views: 228


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-8658 (Print)