Sphingolipid metabolism in colorectal adenomas varies depending on histological architecture of polyps and grade of nuclear dysplasia.

PMID 25595595


Incidence of colorectal cancer (CRC) is growing worldwide. Pathogenetic mechanisms responsible for its onset and progression need further clarification. Colorectal adenomatous polyps are precancerous lesions with malignant potential dependent on histological architecture and grade of nuclear dysplasia. One of the factors conditioning CRC development are abnormalities in sphingolipid metabolism. The aim of this study was to assess the levels of sphingolipids in human colorectal adenomas. The control group (C, n = 12) consisted of patients with no colonic polyps. The examined group consisted of patients with prior diagnosed colonic polyps, qualified to endoscopic polypectomy. This group was further divided due to histological architecture into tubular adenomas group (TA, n = 10), tubulovillous adenomas with low-grade dysplasia (LGD-TVA, n = 10), and tubulovillous adenomas group with high-grade dysplasia (HGD-TVA, n = 11). In tissue samples, sphingolipd metabolite contents were measured using high performance liquid chromatography (HPLC). In cases of polypoid lesions with low malignancy potential (tubular adenomas), concentration of ceramide, which is characterized by proapoptotic and anti-proliferative properties, increases compared with control group (p < 0.05), whereas content of sphingosine-1-phosphate with anti-apoptotic and stimulating cellular proliferation properties is reduced in comparison with control group (p < 0.05). On the contrary, in cases of more advanced form of adenomatous polyps (tubulovillous adenomas with high-grade dysplasia), the ceramide level decreases compared with control group (p < 0.05) while sphingosine-1-phosphate concentration is elevated (p < 0.05). We found that concentrations of pro-apoptotic ceramide are decreased and pro-proliferative S1P levels are increased in polypoid lesions with high malignancy potential, and it was the opposite in those with low malignancy potential.