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. 2023 May 19;8:187. doi: 10.1038/s41392-023-01405-8

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — High levels of CSN6/FASN correlate with poor survival of CRC, suggesting a treatment strategy of orlistat administration. a Representative IHC images of CSN6 and FASN in human 103 CRC tissue microarray samples (left). Scale bars, 50 μm. Correlation of FASN and CSN6 staining through statistical analysis was shown (right). b Kaplan–Meier survival curves of overall survival time based on CSN6 and FASN expression from TMA analysis. The receiver operating characteristic curve was used to define the cutoff, and log-rank analysis was used to test for significance. c Representative immunofluorescent images for CSN6 (green) DAPI (Blue), and FASN (red) in frozen section of colorectal cancer tissue of primary site, adjacent normal tissue, and liver metastasis tissue from same colorectal cancer patient (left). Relative protein expression was quantitated by Image J and presented as bar graphs (right). Scale bar, 50 μm. d Scheme of experimental design for colorectal patient-derived xenografts (PDXs), treatment schedule of FASN inhibitor orlistat and in vivo fatty acid measurement of tumors is indicated (top). P1, passage 1; P2, passage 2; P3, passage 3. Representative IHC images of CSN6 and FASN in indicated PDXs (bottom). Quantification of CSN6 and FASN expression was indicated. e Relative levels of Stearate/Oleate based on ¹³C-glucose metabolite tracing in two PDX cases. f Impact of orlistat on tumor growth in mice bearing indicated PDXs. g Fluorescence microscopy analysis of frozen sections from indicated PDX tumors stained with BODIPY 493/503 dye (green) and DAPI (blue). Representative images (left) and fluorescent BODIPY quantification (right) of indicated groups were shown. Scale bar, 20 μm. h Representative IHC images of cleaved-caspase 3 and Ki67 staining in indicated PDX tumors (left). Scale bars, 50 μm. Quantification of the percentage of Cleaved-caspase 3 and Ki67 positive cells of indicated groups was shown (right). All values are expressed as means ± SD. ns, not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; as determined by two-way ANOVA (f), by one-way ANOVA (c, d, g, h) or by two-sided Student’s t-test (e)