Abstract
Much attention is paid to different sphingolipid pathways because of their possible use in diagnostics and treatment. However, the activity status and significance of ceramide pathways in colorectal cancer are still unclear. We analyzed colorectal cancer patients to evaluate sphingolipid profiles in the blood, colorectal cancer (CRC) tissues, and healthy surrounding colorectal tissues of the same patient, simultaneously, using liquid chromatography coupled with triple quadrupole mass spectrometry. Furthermore, we measured protein expression of de novo ceramide synthesis enzymes and mitochondrial markers in tissues using western blot. We confirmed the different sphingolipid contents in colorectal cancer tissue compared to healthy surrounding tissues. Furthermore, we showed changed amounts of several ceramides in more advanced colorectal cancer tissue and found a prominently higher circulating level of several of them. Moreover, we observed a relationship between the amounts of some ceramide species in colorectal cancer tissue and plasma depending on the stage of colorectal cancer according to TNM (tumors, nodes, metastasis) classification. We think that the combined measurement of several ceramide concentrations in plasma can help distinguish early-stage lesions from advanced colorectal cancer and can help produce a screening test to detect early colorectal cancer.
Highlights
Every year, colorectal cancer (CRC) is diagnosed in over a million people worldwide [1]
We evaluated the profile of ceramides in colorectal cancer tissue and healthy colorectal tissue from the areas surrounding a tumor to better understand sphingolipid metabolism in the development and progression of colorectal cancer
Our analysis showed a different qualitative and quantitative ceramide profile within the colorectal cancer tissue compared to healthy intestinal tissue
Summary
Colorectal cancer (CRC) is diagnosed in over a million people worldwide [1]. A continuous increase in morbidity is observed in many countries, including Poland, where CRC kills 40 people every day. Stable or decreasing trends are only observed in countries with the highest social and economic development indexes [2]. This reduction in mortality is probably due to improved access to endoscopy and improvements in specialized surgical and oncological care. As early colorectal cancer is fully curable, while the management of the more advanced disease is associated with increased morbidity. Since colorectal cancer is a very serious clinical problem and an effective treatment method is still lacking, it is highly important to know all aspects of its cell metabolism to discover new diagnostic and therapeutic targets
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