Characteristics Of Polyunsaturated Fatty Acid Metabolism In Colorectal Cancer And Relationship With Clinical Pathological Factors

Objective To investigate the Characteristics of polyunsaturated fatty acid distributionin colorectal cancer, the correlation with inflammatory factor and the relationship withclinical pathological significance, and to evaluate the effects of ω-3and-6PUFA in thediagnosis and treatment.Methods Fresh frozen benign and malignant colorectal tissues were obtained from82patients and blood samples were detected in38patients in PLA general hospital in2010.The PUFA composition in these samples was determined by gas-liquid chromatographyon a capillary column. The results were obtained through the ELISA including VEGF,COX-2, PGE2and PDGF. The relationship between the PUFA level and suchclinicopathological profiles as age, gender, location, differentiation degree, TNM (tumor,node, and metastasis) stage, VEGF, Ki-67and P53were analyzed.Results1. The total levels of ω-6PUFA and tissue levels of LA (C18:2n-6)(P=0.00)were lower. But the total levels of ω-3PUFA and tissue levels of DGLA (20:3ω-6)(P=0.000) were signifcantly higher in malignant (P=0.000). The ratio of AA/LA(P=0.000), and AA/the total levels of ω-6PUFA (P=0.002) were signifcantly higher inmalignant.2. Metabolism of Omega-6PUFA dominated in PUFA metabolism path. The ratio ofω-6/ω-3was4.89in blood sample and10.15in tissue. The ratio of ω-6/ω-3LC-PUFAswas2.86in blood sample and4.51in tissue. The D6D activity index in ω-6PUFAmetabolic processes both in tissue (t=11.609,P=0.00) and blood sample(t=-9.151,P=0.00) was higher than in ω-3PUFA.3. In malignant tissue, PDGF、COX-2and VEGF showed a signifcant increasecompared with those in the normal(P＜0.05). And COX-2were inverse relations withLA, and positive withAA/the total levels of ω-6PUFA, the ratio ofAA/LA(P＜0.05). 4. Tissue level of AA in patients aged over60yesrs was signifcantly lower(0.12%±0.06%, P=0.045). In patients with tumor size <5cm tissue level of EPA wassignifcantly higher (0.29%±0.13%, P=0.030), while ω-6/ω-3PUFA was lower(10.8±2.6, P=0.031). Significant statistical difference existed in tissue level of LA,AA/ω-3PUFA in different differentiation degree (P=0.013,0.027). Tissue level of LAin poorly differentiated tumor was highest (19.9%±6.3%, P<0.05), while AA/ω-3PUFA lowest (4.1±2.0, P<0.05). Tissue level of LA was higher in VEGF-positivetumors than those in VEGF-negative counterparts(16.2%±3.7%, P=0.009), while theratio of AA/ω-3PUFA, AA/ω-6PUFA, AA/LA in VEGF-positive tumors were lowerthan those in VEGF-negative（5.0±1.8,0.30±0.09,0.50±0.21, P=0.004,0.038,0.030）.In Ki-67negative LA was highest (22.5%±10.1%, P=0.048). No significant differencesexisted in the level of PUFA among the gender, the clinical pathological stage, lymphnode metastasis and groups with different expression of P53.Conclusion We found that the metabolism of PUFA in malignant colorectal tissues isdifferent from benign tissues, and plays an important role in the development ofinflammation-driven tumorigenesis in the colorectal tumor. We found that in colorectalcarcinoma the ω-6PUFA metabolic not only plays an important role in the metabolismof PUFA, but also is more active than the ω-3PUFA metabolic. The tissue levels ofPUFA are somewhat correlated with the clinicopathologic parameters of CRC and thedevelopment of tumorigenesis in the colorectal tumor.