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无细胞染色质免疫沉淀可确定肺癌患者的肿瘤基因表达。

Cell-free chromatin immunoprecipitation can determine tumor gene expression in lung cancer patients.

机构信息

Department of Clinical Biochemistry, Faculty of Health, Aarhus University Hospital, Denmark.

Department of Clinical Medicine, Aarhus University, Denmark.

出版信息

Mol Oncol. 2023 May;17(5):722-736. doi: 10.1002/1878-0261.13394. Epub 2023 Mar 5.

DOI:10.1002/1878-0261.13394
PMID:36825535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10158780/
Abstract

Cell-free DNA (cfDNA) in blood plasma can be bound to nucleosomes that contain post-translational modifications representing the epigenetic profile of the cell of origin. This includes histone H3 lysine 36 trimethylation (H3K36me3), a marker of active transcription. We hypothesised that cell-free chromatin immunoprecipitation (cfChIP) of H3K36me3-modified nucleosomes present in blood plasma can delineate tumour gene expression levels. H3K36me3 cfChIP followed by targeted NGS (cfChIP-seq) was performed on blood plasma samples from non-small-cell lung cancer (NSCLC) patients (NSCLC, n = 8), small-cell lung cancer (SCLC) patients (SCLC, n = 4) and healthy controls (n = 4). H3K36me3 cfChIP-seq demonstrated increased enrichment of mutated alleles compared with normal alleles in plasma from patients with known somatic cancer mutations. Additionally, genes identified to be differentially expressed in SCLC and NSCLC tumours had concordant H3K36me3 cfChIP enrichment profiles in NSCLC (sensitivity = 0.80) and SCLC blood plasma (sensitivity = 0.86). Findings here expand the utility of cfDNA in liquid biopsies to characterise treatment resistance, cancer subtyping and disease progression.

摘要

血浆中的无细胞 DNA (cfDNA) 可以与含有代表起源细胞表观遗传特征的翻译后修饰的核小体结合。这包括组蛋白 H3 赖氨酸 36 三甲基化 (H3K36me3)，一种转录活性的标志物。我们假设在血浆中存在的带有 H3K36me3 修饰的核小体的无细胞染色质免疫沉淀 (cfChIP) 可以描绘肿瘤基因表达水平。对非小细胞肺癌 (NSCLC) 患者 (NSCLC，n=8)、小细胞肺癌 (SCLC) 患者 (SCLC，n=4) 和健康对照者 (n=4) 的血浆样本进行了 H3K36me3 cfChIP 后靶向 NGS (cfChIP-seq)。H3K36me3 cfChIP-seq 表明，与已知体细胞癌症突变患者血浆中的正常等位基因相比，突变等位基因的富集程度增加。此外，在 SCLC 和 NSCLC 肿瘤中差异表达的基因在 NSCLC (敏感性=0.80) 和 SCLC 血浆 (敏感性=0.86) 中具有一致的 H3K36me3 cfChIP 富集谱。这些发现扩展了 cfDNA 在液体活检中的用途，以表征治疗耐药性、癌症亚型和疾病进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/680d3728952b/MOL2-17-722-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/624a10270375/MOL2-17-722-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/9683aad0aa67/MOL2-17-722-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/82a2a862d6ab/MOL2-17-722-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/680d3728952b/MOL2-17-722-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/624a10270375/MOL2-17-722-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/9683aad0aa67/MOL2-17-722-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/82a2a862d6ab/MOL2-17-722-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/311a/10158780/680d3728952b/MOL2-17-722-g001.jpg

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