Expression profile of polyunsaturated fatty acids in colorectal cancer.

Abstract

To investigate the relationship between the metabolism of polyunsaturated fatty acids (PUFAs) and tumor-associated factors for predicting the outcome of colorectal carcinoma (CRC) in Chinese patients. Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography. The levels of vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), prostaglandin E2 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay, and the levels of VEGF, p53 and Ki-67 were measured by immunohistochemistry. In malignant tissue, compared with normal tissue, the levels of total ω-6 PUFAs (24.64%±3.41% vs 26.77%±3.37%, P=0.00) and linoleic acid (LA) (15.46%±3.51% vs 18.30%±2.83%, P<0.01) were lower, whereas the levels of total ω-3 PUFAs (1.58%±0.74% vs 1.35%±0.60%, P<0.01) and dihomo-gamma-linolenic acid (DGLA) (1.32%±0.69% vs 0.85%±0.29%, P<0.01) were significantly higher. The ratios of arachidonic acid (AA)/LA (0.53±0.22 vs 0.42±0.19, P<0.01) and AA/total ω-6 PUFAs (0.31±0.09 vs 0.27±0.10, P<0.01) were also significantly higher in malignant tissue. The levels of PDGF (353.10±148.85 pg/mL vs 286.09±104.91 pg/mL, P<0.01), COX-2 (125.21±70.29 ng/mL vs 67.06±42.22 ng/mL, P<0.01) and VEGF (357.11±128.76 pg/mL vs 211.38±99.47 pg/mL, P<0.01) were also higher in malignant tissue compared to normal tissue. COX-2 was inversely correlated with LA (R=-0.3244, P<0.05) and positively correlated with AA/total ω-6 PUFAs (R=0.3083, P<0.05) and AA/LA (R=0.3001, P<0.05). The tissue level of LA was highest in poorly differentiated tumors (19.9%±6.3%, P<0.05), while the ratio of AA/ω-3 PUFAs was lowest in these tumors (10.8±2.6, P<0.05). In VEGF-positive tumors, the level of LA was higher (16.2%±3.7% vs 13.9%±2.7%, P<0.01), while the AA/ω-3PUFA, AA/ω-6 PUFA, and AA/LA ratios were lower than in VEGF-negative tumors (5.0±1.8 vs 6.7±3.3, 0.30±0.09 vs 0.34±0.09, 0.50±0.21 vs 0.61±0.21, P<0.01). The metabolism of PUFAs may play an important role in the evolution of inflammation-driven tumorigenesis in CRC and may be considered a potential marker for prognosis.