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韩国队列中结直肠癌的综合 RNA 测序分析。

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort.

机构信息

Department of Surgery, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 11765, Republic of Korea.

Korea Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.

出版信息

Mol Cells. 2024 Mar;47(3):100033. doi: 10.1016/j.mocell.2024.100033. Epub 2024 Feb 23.

DOI:10.1016/j.mocell.2024.100033
PMID:38403196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11004400/
Abstract

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

摘要

考虑到韩国结直肠癌(CRC)病例数量的近期增加,我们旨在阐明韩国人群 CRC 特有的分子特征。为了深入了解 CRC 的复杂性并促进关键数据的交流,我们进行了 RNA 测序分析,以揭示驱动 CRC 发展和进展的分子机制;这对于开发有效的治疗策略至关重要。我们对 214 名韩国参与者的 CRC 和相邻正常组织样本进行了 RNA 测序分析(总共 381 个样本,包括 169 个正常样本和 212 个肿瘤样本),以研究两组之间的差异基因表达。我们鉴定了在 CRC 和正常组织中表达的 19575 个基因,其中有 3830 个差异表达基因(DEGs)。功能注释分析表明,上调的 DEGs 显著富集在与细胞周期、DNA 复制和 IL-17 相关的途径中,而下调的 DEGs 则富集在代谢途径中。我们还使用共识分子亚型(CMS)分类分析了临床信息与亚型之间的关系。此外,我们比较了在我们的数据集内聚类的组与 CMS 组,并对 DEGs 和 CMS 组之间的甲基化数据进行了额外的分析,以从各个角度提供全面的生物学见解。我们的研究提供了对韩国患者 CRC 分子机制的有价值的见解,并为识别这种疾病的潜在靶基因提供了一个平台。原始数据和处理结果已存入公共存储库,以供进一步分析和探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/0370c97fe1b1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/16dd35b3303a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/40a9c60a2a9f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/fcc4ad8d863e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/8221a21c2e5f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/0370c97fe1b1/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/16dd35b3303a/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/40a9c60a2a9f/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/fcc4ad8d863e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/8221a21c2e5f/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e13e/11004400/0370c97fe1b1/gr5.jpg

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本文引用的文献

1
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BMB Rep. 2024 Mar;57(3):161-166. doi: 10.5483/BMBRep.2023-0103.
2
Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis.共识分子亚型在结直肠癌中的临床价值:系统评价和荟萃分析。
J Natl Cancer Inst. 2022 Apr 11;114(4):503-516. doi: 10.1093/jnci/djab106.
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Methylation-Based Therapies for Colorectal Cancer.
秀丽隐杆线虫的趋化反应是一种很有前景的癌症早期检测工具。
Discov Oncol. 2024 Dec 20;15(1):817. doi: 10.1007/s12672-024-01721-7.
基于甲基化的结直肠癌治疗方法。
Cells. 2020 Jun 24;9(6):1540. doi: 10.3390/cells9061540.
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IL-17 and colorectal cancer: From carcinogenesis to treatment.白细胞介素-17 与结直肠癌:从癌变到治疗。
Cytokine. 2019 Apr;116:7-12. doi: 10.1016/j.cyto.2018.12.021. Epub 2019 Jan 23.
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CMScaller: an R package for consensus molecular subtyping of colorectal cancer pre-clinical models.CMScaller:一个用于共识分子分型的 R 包,用于结直肠癌临床前模型。
Sci Rep. 2017 Nov 30;7(1):16618. doi: 10.1038/s41598-017-16747-x.
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Poor survival in stage IIB/C (T4N0) compared to stage IIIA (T1-2 N1, T1N2a) colon cancer persists even after adjusting for adequate lymph nodes retrieved and receipt of adjuvant chemotherapy.与IIIA期(T1-2 N1、T1N2a)结肠癌相比,IIB/C期(T4N0)结肠癌患者的生存率较低,即便在对获取的足够数量的淋巴结以及辅助化疗的接受情况进行调整之后,这种情况仍然存在。
BMC Cancer. 2016 Jul 13;16:460. doi: 10.1186/s12885-016-2446-3.
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Complex heatmaps reveal patterns and correlations in multidimensional genomic data.复杂热图揭示多维基因组数据中的模式和相关性。
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