Erythrocyte membrane fatty acids as the potential biomarkers for detection of early-stage and progression of colorectal cancer
Authors: M. Kruchinina, A. Gromov, Y. Prudnikova, M. Shashkov, A. Sokolova, V. Kruchinin
Journal: Annals of Oncology (2018)

Introduction: Colorectal cancer (CRC) is the third most common cancer in the world. Clinical data show that 5-year survival rate of early-stage CRC postoperative patients is around 90%. However, most of CRC patients were diagnosed at advanced stage due to its asymptomatic and poor diagnostic techniques. Early screening is an effective way to reduce the morbidity and mortality. So, it is necessary to develop low-cost, less invasive, high-sensitivity, and high-specificity screening methods for early diagnosis of CRC and its progression. The study aims to assess erythrocyte membrane fatty acids (FA) as the potential biomarkers for detection of early-stage from healthy controls and progression of colorectal cancer (CRC). Methods: Erythrocyte membrane FA from 95 patients (56 + 8 years old) with colorectal adenocarcinoma and 28 healthy people (the control group) were measured using an accelerated solvent extraction and analyzed by GC/MS system triple quad Agilent 7000B (USA). Tumors were further classified into early stage (stage I or II, n = 44) and advanced stage (stage III or IV, n = 51) based on TNM classification. Results: Erythrocyte membrane levels of C14:0 (p < 0.03), C15:0 (p < 0.04), C17:0 (p < 0.02), the sum of saturated FA (p < 0.03), C16:1 (p < 0.04), the sum of monounsaturated FA (p < 0.01), C18:2 (p < 0.01), omega-6/omega-3 (p < 0,01) in early stage CRC patients were significantly decreased compared with healthy controls, whereas the levels of C20:0 (p < 0.01), C20:2, (p < 0.01), C20:3 (p < 0.001), C20:4 (p < 0.001), C22:4 (p < 0.001), C22:5 (p < 0.001), C22:6 (p < 0.001) and the sum of all unsaturated FA (p < 0,03) were significantly higher than those from the controls. CRC progression was accompanied by decrease in the content of saturated, monounsaturated as well as by increase polyunsaturated fatty acids (p < 0.001-0.05). Elevated levels of polyunsaturated fatty acids as structural components of membranes reflect a high level of their instability, which is probably associated with the process of tumor proliferation. In contrast, a decrease in the level of saturated fatty acids may be due to their consumption as an energy substrate for rapid metabolism which is necessary for tumor growth. As saturated FA do not require creation of a double bond within the beta-oxidation process it allows them for an accelerated energy production. The panel, containing the FA - C17:0, C16:1, C18:2, C20:4, C22:5, C22:6 - achieved an excellent diagnostic performance when comparing early stage patients with healthy controls with an AUC of 0.959, a sensitivity of 86.5%, and a specificity of 96.2%. A combination of C16:0, C18:1;t9, C18:3, C20:2, C20:4, C20:5, C22:5, C22:6 showed the best diagnostic ability when comparing the late stage CRC patients with early stages (AUC 0.871, sensitivity of 82.7%, specificity of 80.8%. Conclusion: Erythrocyte levels of the fatty acids should be considered as the promising biomarkers for detecting of early stages of CRC and the progression of the disease.