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外周血免疫细胞中的 5-甲基胞嘧啶（mC）修饰是一种新型的结直肠癌诊断的非侵入性生物标志物。

5-Methylcytosine (mC) modification in peripheral blood immune cells is a novel non-invasive biomarker for colorectal cancer diagnosis.

机构信息

Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.

Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.

出版信息

Front Immunol. 2022 Sep 21;13:967921. doi: 10.3389/fimmu.2022.967921. eCollection 2022.

DOI:10.3389/fimmu.2022.967921
PMID:36211353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9532581/
Abstract

Current non-invasive tumor biomarkers failed to accurately identify patients with colorectal cancer (CRC), delaying CRC diagnosis and thus leading to poor prognosis. Dysregulation of 5-Methylcytosine (mC) RNA has gradually been reported in various cancers, but their role in tumor diagnosis is rarely mentioned. Our study aimed to determine the role of mC methylation modification in blood immune cells for the diagnosis of CRC. Peripheral blood samples were obtained from a total of 83 healthy controls and 196 CRC patients. We observed that mC RNA contents in blood immune cells of CRC patients were markedly enhanced in both training set and validation set. Moreover, levels of mC increased with CRC progression and metastasis but reduced after treatment. Compared with common blood tumor biomarkers, mC levels in peripheral blood immune cells had superior discrimination and reclassification performance in diagnosing CRC. Besides, bioinformatics and qRT-PCR analysis identified increased expression of mC-modified regulators NSUN5 and YBX1 in CRC patients' blood. A series of animal models and cell co-culture models further demonstrated that CRC tumor cells could increase immune cells' mC levels and mC-modified regulators. Monocyte was the predominant mC-modified immune cell type in CRC patients' blood by Gene set variation analysis (GSVA). Taken together, mC methylation modification in peripheral blood immune cells was a promising biomarker for non-invasive diagnosis of CRC.

摘要

目前的非侵入性肿瘤生物标志物未能准确识别结直肠癌 (CRC) 患者，导致 CRC 诊断延迟，从而导致预后不良。5-甲基胞嘧啶 (mC) RNA 的失调在各种癌症中逐渐被报道，但它们在肿瘤诊断中的作用很少被提及。我们的研究旨在确定 mC 甲基化修饰在血液免疫细胞中对 CRC 诊断的作用。共从 83 名健康对照者和 196 名 CRC 患者中获得外周血样本。我们观察到 CRC 患者血液免疫细胞中的 mC RNA 含量在训练集和验证集中均明显增加。此外，mC 水平随着 CRC 的进展和转移而增加，但治疗后降低。与常见的血液肿瘤生物标志物相比，外周血免疫细胞中的 mC 水平在诊断 CRC 方面具有更好的区分和再分类性能。此外，生物信息学和 qRT-PCR 分析鉴定出 CRC 患者血液中 mC 修饰调节剂 NSUN5 和 YBX1 的表达增加。一系列动物模型和细胞共培养模型进一步表明，CRC 肿瘤细胞可以增加免疫细胞的 mC 水平和 mC 修饰调节剂。通过基因集变异分析 (GSVA)，单核细胞是 CRC 患者血液中主要的 mC 修饰免疫细胞类型。总之，外周血免疫细胞中的 mC 甲基化修饰是一种有前途的非侵入性 CRC 诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/c96f30e60317/fimmu-13-967921-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/338c5b173199/fimmu-13-967921-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/432edd91b2ba/fimmu-13-967921-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/0425f2a9774a/fimmu-13-967921-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/dbd045b8e657/fimmu-13-967921-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/ecdbd2e36faf/fimmu-13-967921-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/c96f30e60317/fimmu-13-967921-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/338c5b173199/fimmu-13-967921-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/432edd91b2ba/fimmu-13-967921-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/0425f2a9774a/fimmu-13-967921-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/dbd045b8e657/fimmu-13-967921-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/ecdbd2e36faf/fimmu-13-967921-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/79c2/9532581/c96f30e60317/fimmu-13-967921-g006.jpg

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