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类器官在模拟结肠腺瘤-癌序列方面存在局限性。

Organoids Are Limited in Modeling the Colon Adenoma-Carcinoma Sequence.

机构信息

Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.

Department of Surgical Oncology, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.

出版信息

Cells. 2021 Feb 25;10(3):488. doi: 10.3390/cells10030488.

DOI:10.3390/cells10030488
PMID:33668713
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7996178/
Abstract

The colon adenoma-carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma-carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma-carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cells were different between tissues and organoids, whereas there was no difference between cancer and adenoma organoids. The amounts of cancer stem cells and progenitor cells were not different between CRC and adenoma organoids, whereas a difference was noted between CRC and adenoma tissues. In conclusion, we demonstrated that organoids model only part of the adenoma-carcinoma sequence and should be used with caution after considering their limitations.

摘要

结肠腺瘤-癌序列是结直肠癌（CRC）发生过程中发生的多步骤基因组改变过程。类器官现在常用于模拟非癌性和癌性组织。本研究旨在通过比较转录组来研究类器官在多大程度上模拟腺瘤-癌序列中的组织。共分析了 234 个组织样本（48 个腺瘤和 186 个 CRC）和 60 个类器官样本（15 个腺瘤和 45 个 CRC）。我们发现，通过基因集富集分析（GSEA），与腺瘤组织和类器官相比，CRC 组织和类器官中与细胞增殖相关的基因集始终富集。在 CRC 类器官中没有发现已知的结肠腺瘤-癌序列中的途径始终富集。CRC 类器官中没有肿瘤微环境相关基因集的富集。CRC 组织富集免疫反应相关基因集，而 CRC 类器官则没有。浸润免疫细胞的比例在组织和类器官之间存在差异，而在癌症和腺瘤类器官之间则没有差异。CRC 组织和腺瘤组织中的癌症干细胞和祖细胞数量没有差异，而在 CRC 和腺瘤组织之间存在差异。总之，我们证明类器官仅模拟了腺瘤-癌序列的一部分，在考虑其局限性后应谨慎使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/bcafcac1cd30/cells-10-00488-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/6c78ad989a29/cells-10-00488-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/4c663a49cb73/cells-10-00488-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/8bf8d70d15d7/cells-10-00488-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/0182d0859ce3/cells-10-00488-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/88eedce85c82/cells-10-00488-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/f37f7e62ebe1/cells-10-00488-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/bcafcac1cd30/cells-10-00488-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/6c78ad989a29/cells-10-00488-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/4c663a49cb73/cells-10-00488-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/8bf8d70d15d7/cells-10-00488-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/0182d0859ce3/cells-10-00488-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/88eedce85c82/cells-10-00488-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/f37f7e62ebe1/cells-10-00488-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64ad/7996178/bcafcac1cd30/cells-10-00488-g007.jpg

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