Perturbation of Fatty Acids of Erythrocyte Membranes and Blood Serum in Patients with Colorectal Cancer: New Opportunities for Diagnostics
Доклады на конференциях
The aim of the study was to investigate the perturbation of fatty acids (FA) of erythrocyte (RBC) phospholipid membrane and blood serum (BS) in order to find peculiarities which could be used for early screening, determination of progression of colorectal tumour of various localization and to reveal changing trends in CRC-related FA.
The CRC patients (63,2+9,4 years old) included 64 patients with early stage (TNM staging I, II), 59 with late stage (TNM staging III, IV) and various tumor locations. Late stage patients contain TNM staging III and IV with lymph node or distant metastases of various localizations (n=14 - liver-only, n=12 – extrahepatic). The healthy controls (n=35, 61,7+7,5 years old) were selected by routine clinical examination. RBC membrane and BS FA percentages were measured using GC/MS system triple quad Agilent 7000B (USA).
A total of 21 differentially expressed FA in RBC membrane and BS were identified. Each FA class demonstrated specific changing trends in CRC progression (down-regulation in saturated, monounsaturated (MUFA) and up-regulation in PUFA during cancer progression).
Significantly lower value of RBC C16:2 (p=0.015), C18:2 (p=0.004), C20:2 (p=0.011), C20:3 (p=0.025) and serum C18:3 (p=0.002), n-6/n-3 (p=0.04) as compared to distal tumour localization, has been noted for patients with proximal tumors. However the higher level of erythrocytes C18:1 (p=0.035), amount of MUFA (p=0.02) were observed in CRC patients with proximal tumors than those with distal. In patients with proximal tumours, lower mean level of RBC C20:5 (p<0.05) and serum C20:3 (p=0.04), C20:4 (p<0.05) as compared to patients with distal tumor were noted only for patients with disease progression.
The revealed FA differences, associated with the stage of the disease, tumour localization served as the basis for development of diagnostic panels enabling to verify the CRC patients.
The panel 1 containing FA of RBC and BS: C20:2, C20:3, С20:4, С22:4, С22:5, С22:6 - achieved high diagnostic accuracy (0,79) with AUC of 0.86, a sensitivity of 0.78 and a specificity of 0.87 for differentiating early stage patients from healthy controls (OR 19,4 (0,17;0,55), which was better than the carcinoembryonic antigen biomarker. The combination of two diagnostic panels, including RBC FA - С20:2, С20:3, С20:4, С22:4, С22:5, С22:6 and BS FA - С20:3, С20:4, С22:6 - showed the best predictive power when comparing the II stage CRC patients (AUC 0.82, diagnostic accuracy 0.81, sensitivity 0.73, specificity 0.86, OR 16.9) and III stage (AUC 0.84, diagnostic accuracy 0.80, sensitivity 0.76, specificity 0.86, OR 19.4) with healthy controls. The model 2 (FA of RBC - С 14:0, С16:0, С16:1, С18:1, С20:3, С20:4, С22:4, С22:5, С22:6) allowed us to determine the presence of distant metastases (AUC 0.83, OR=2.29). Probably, FA modifications are essential for correct signaling, including Hh, Wnt pathways, so perturbation of FA are closely associated with carcinogenesis.