Fatty acids of erythrocyte membranes and blood serum as biomarkers for early detection of colorectal cancer

Author:

Kruchinina M. V.1ORCID,Kruchinin V. N.2ORCID,Gromov A. A.3ORCID,Shashkov M. V.4ORCID,Sokolova A. S.5ORCID,Yakovina I. N.6ORCID,Shestov A. A.7

Affiliation:

1. Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the RAS; Novosibirsk State Medical University

2. Rzhanov Institute of Semiconductor Physics, Siberian Branch of the RAS

3. Research Institute of Internal and Preventive Medicine – Branch of the Institute of Cytology and Genetics, Siberian Branch of the RAS

4. Boreskov Institute of Catalysis, Siberian Branch of the RAS

5. N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the RAS

6. Novosibirsk State Technical University

7. University of Pennsylvania

Abstract

The aim of the study was to identify fatty acids (FA) of erythrocyte membranes and blood serum, which can serve as potential biomarkers for early detection of colorectal cancer.Material and methods. the study involved 65 patients with stage I-II CRC (mean age 63,3 ± 9,6 years (30 men, 35 women) and 35 people in the comparison group, matched by age and sex. the composition of fatty acids of erythrocyte membranes and blood serum was studied using a gc/ms system based on three agilent 7000B quadrupoles (USA). methods of the MATLAB software (R2019a, MathWorks) and the R programming language were used for statistical processing: t-test, unsupervised principal component analysis (PCA), Fold change, Volcano plot, machine learning method (Random Forest), Roc analysis, Heatmaps.Results. patients with stage I-II CRC showed a decrease in the level of saturated, individual monounsaturated fatty acids and a highly significant increase in the most of the polyunsaturated fatty acids with a predominance of omega-3. For most of the fatty acid levels, significant differences in erythrocyte membranes and serum between the groups were found. the levels of erythrocyte myristic, pentadecanoic, 7-palmitoleic, saturated/polyunsaturated Fa ratios (the content of which was significantly lower at stages I-II CRC than those in the control) and the levels of α-linolenic, eicosapentaenoic, docosapentaenoic, docosahexaenoic, the amount of omega-3 Fa, EPA + DHA, docodienic, dihomo-γ-linolenic, docatetraenoic fatty acids (the content of which was significantly higher in colorectal cancer than those in healthy subjects) were the most discriminating parameters in distinguishing patients with I-II stage CRC and healthy individuals. in the blood serum, the level of biomarkers had the following fatty acids: arachidonic, myristic, docosahexaenoic, the amount of omega 3 puFa, the ratio of omega 6/omega 3 puFa, pentadecanoic, docosapentaenoic, and docodiene. a model that included a list of fatty acids, such as С14:0, С15:0, С16:1;7, С18:3 n-3, C20:2 n-6, C20:3 n-6, C20:5 n-3, C22:4 n-6, C22:5 n-3, C22:6 n-3, sum of omega-3, omega-3 (EPA + DHA), and saturated / polyunsaturated fatty acids ratio provided auc 0,916 with a specificity of 0,90 and sensitivity of 0,95 in distinguishing patients with stage I-II CRC from healthy individuals.Conclusion. the study of the levels and ratios of fatty acids in erythrocyte membranes and blood serum should be considered a promising trend in the search for biomarkers for the early diagnosis of colorectal cancer.

Publisher

Tomsk Cancer Research Institute

Subject

Cancer Research,Oncology

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