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结直肠癌腺瘤和癌症的综合表观基因组-转录组图谱早期结果

Early results of the integrative epigenomic-transcriptomic landscape of colorectal adenoma and cancer.

作者信息

Lu You-Wang, Ding Zhao-Li, Mao Rui, Zhao Gui-Gang, He Yu-Qi, Li Xiao-Lu, Liu Jiang

机构信息

Department of Dermatology and Venereology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China.

Kunming Biological Diversity Regional Center of Large Apparatus and Equipments, Public Technical Service Center, Kunming Institute of Zoology, Kunming 650223, Yunnan Province, China.

出版信息

World J Gastrointest Oncol. 2024 Feb 15;16(2):414-435. doi: 10.4251/wjgo.v16.i2.414.

DOI:10.4251/wjgo.v16.i2.414
PMID:38425399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10900154/
Abstract

BACKGROUND

Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value.

AIM

To identify potential DNA methylation markers specific to ADE and CRC.

METHODS

Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.

RESULTS

Comparing 22 CRC and 25 ADE samples, global methylation was higher in the former, but both showed similar methylation patterns regarding differentially methylated gene positions, chromatin signatures, and repeated elements. High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC. Combined with RNA-seq gene expression data, we identified 14 methylation-regulated differentially expressed genes, of which only and methylation had prognostic significance.

CONCLUSION

Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC, suggesting prognostic biomarkers for CRC.

摘要

背景

异常甲基化在结直肠癌（CRC）的发生和发展过程中很常见，检测这些在早期腺瘤（ADE）形成和CRC进展过程中发生的变化具有临床价值。

目的

鉴定特定于ADE和CRC的潜在DNA甲基化标志物。

方法

在此，我们对结直肠ADE和CRC样本进行了SeqCap靶向亚硫酸氢盐测序和RNA测序分析，以描绘表观基因组-转录组图谱。

结果

比较22个CRC样本和25个ADE样本，前者的整体甲基化水平更高，但在差异甲基化基因位置、染色质特征和重复元件方面，两者显示出相似的甲基化模式。与低级别CRC相比，高级别CRC在基因启动子区域的甲基化水平往往更高。结合RNA测序基因表达数据，我们鉴定出14个甲基化调控的差异表达基因，其中只有 和 甲基化具有预后意义。

结论

我们的结果表明，DNA甲基化的全基因组改变发生在CRC的早期阶段，并证明了与结直肠ADE和CRC相关的甲基化特征，提示了CRC的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/8fadc078bc54/WJGO-16-414-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/86f837215a35/WJGO-16-414-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/716f1e5cedac/WJGO-16-414-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/c823d2d4f86d/WJGO-16-414-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/e803e806399f/WJGO-16-414-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/eae35a050d94/WJGO-16-414-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/a34c2bef684e/WJGO-16-414-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/96a91d042750/WJGO-16-414-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/8fadc078bc54/WJGO-16-414-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/86f837215a35/WJGO-16-414-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/716f1e5cedac/WJGO-16-414-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/c823d2d4f86d/WJGO-16-414-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/e803e806399f/WJGO-16-414-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/eae35a050d94/WJGO-16-414-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/a34c2bef684e/WJGO-16-414-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/96a91d042750/WJGO-16-414-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a35/10900154/8fadc078bc54/WJGO-16-414-g008.jpg

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本文引用的文献

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CpG Site-Based Signature Predicts Survival of Colorectal Cancer.基于CpG位点的特征可预测结直肠癌的生存率。
Biomedicines. 2022 Dec 7;10(12):3163. doi: 10.3390/biomedicines10123163.
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The neuronal protein Neuroligin 1 promotes colorectal cancer progression by modulating the APC/β-catenin pathway.神经元蛋白 Neuroligin 1 通过调节 APC/β-catenin 通路促进结直肠癌的进展。
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Comparison of DNA methylation measurements from EPIC BeadChip and SeqCap targeted bisulphite sequencing in PON1 and nine additional candidate genes.
EPIC BeadChip 与 SeqCap 靶向亚硫酸氢盐测序在 PON1 及其他 9 个候选基因中 DNA 甲基化测量的比较。
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Comprehensive landscape of the renin-angiotensin system in Pan-cancer: a potential downstream mediated mechanism of SARS-CoV-2.泛癌症中肾素-血管紧张素系统的全面分析：SARS-CoV-2 的潜在下游介导机制。
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