Abstract
Endoscopic treatment for early colorectal cancer closely correlates with patient prognosis. However, endoscopic differentiation between carcinomas and non-neoplastic lesions remains difficult. Here, we topically stained colorectal neoplasms with a fatty acid analogue (BODIPY-FA) and quantified the fluorescent signals using confocal laser endomicroscopy (CLE) and fluorescence microscopy. We also analyzed protein expression in colorectal cancer tissues. We found that expression of fatty acid synthase was elevated, while the expression of fatty acid transporters was reduced in colorectal cancer. In colorectal cancer mouse models and patients, the BODIPY-FA signals were higher in normal epithelia than in carcinomas or colonic intraepithelial neoplasias. BODIPY-FA staining revealed both the arrangement of intestinal glands and the intracellular structures under CLE screening. In a double-blind trial, CLE images stained with BODIPY-FA exhibited greater consistency (κ = 0.68) and overall validity (74.65%) than those stained using intravenous fluorescein sodium (κ = 0.43, 55.88%) when the results were compared with histological diagnoses. These findings suggest that topical use of BODIPY-FA with CLE is a promising imaging approach for early colorectal neoplasm screening.
Highlights
Cancer cell metabolism differs significantly from normal cell metabolism
Analysis of data from the Clinical Proteomic Tumor Analysis Consortium indicated that most enzymes involved in de novo fatty acid (FA) synthesis, including fatty acid synthase (FASN), acetylCoA carboxylase (ACC) and ATP citrate lyase (ACLY), were expressed at significantly higher levels in colorectal cancer (CRC) tissues than in normal colorectal tissues
The acetylCoA synthetase complex (ACSc) and carnitine palmitoyl transferase 2 (CPT2) were downregulated in CRC tissues, suggesting that FA oxidation is impaired in colonic carcinoma (Figure 1A and Supplementary Figure 1, detailed in Supplementary Table 4)
Summary
Most proliferating cancer cells take up more glucose and produce more lactate via the glycolytic pathway than normal cells, even when oxygen is abundant [1,2,3,4,5]. This so-called ‘Warburg effect’ has been intensively studied and generally applied in clinical positron emission tomography–computed tomography [6, 7]. Endogenous fatty acid (FA) synthesis ( called de novo FA synthesis) is enhanced in cancer cells, irrespective of the exogenous lipid supply [8,9,10,11]. The practical applications of this phenomenon have not been fully explored
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