来自用户 草莓味儿 的文献。
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1.
草莓味儿
(2022-03-31 21:36):
#paper DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load
DOI: 10.1038/s41467-019-12159-9
本篇文章的研究者对各种肿瘤类型的TCGA数据进行了大规模的系统分析，研究了全局甲基化水平与细胞增殖，突变负荷，SCNA水平，浸润性免疫细胞标记和免疫应答基因活性之间的关系。结果表明作为免疫治疗中重要的预测标志物，基因组去甲基化与表观遗传调控有关，可以作为精确免疫治疗的联合方案。
主要研究内容包括：通过细胞系数据，确定了与正常细胞相比在癌症中更早或更晚复制的基因；另外，晚期复制区的甲基化缺失也称为部分甲基化结构域（PMD），与免疫基因抑制相关；全局甲基化预测免疫疗法的反应：采用肺癌队列测试了由分子分析得出的假设，需要指出的是这是第一项针对癌症免疫疗法的分子和临床数据中的DNA甲基化模式的研究；全局去甲基化排除了非整倍性的影响。总的来说，表观遗传调节和检查点阻断相结合，可以作为一种潜在的精准免疫治疗方案。
IF:14.700Q1
Nature communications,
2019-09-19.
DOI: 10.1038/s41467-019-12159-9
PMID: 31537801
PMCID:PMC6753140
Abstract:
Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in …
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Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy.
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2.
草莓味儿
(2022-02-28 19:00):
#paper Liquid Biopsy to Detect Minimal Residual Disease: Methodology and Impact
# DOI: 10.3390/cancers13215364 这是一篇综述，讨论了通过液体活检在实体肿瘤中检测MRD的不同方法，它们各自的潜力和问题，以及MRD检测对癌症患者管理的临床影响。主要关注ctDNA（循环肿瘤 DNA），这是基于肿瘤特异性基因组改变的MRD的常用检测方法，并且在日常临床实践中已通过NGS方法或PCR方法得以实施。优点：为未来研究个体肿瘤患者的辅助治疗提供依据。
Abstract:
One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by …
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One reason why some patients experience recurrent disease after a curative-intent treatment might be the persistence of residual tumor cells, called minimal residual disease (MRD). MRD cannot be identified by standard radiological exams or clinical evaluation. Tumor-specific alterations found in the blood indirectly diagnose the presence of MRD. Liquid biopsies thus have the potential to detect MRD, allowing, among other things, the detection of circulating tumor DNA (ctDNA), circulating tumor cells (CTC), or tumor-specific microRNA. Although liquid biopsy is increasingly studied, several technical issues still limit its clinical applicability: low sensitivity, poor standardization or reproducibility, and lack of randomized trials demonstrating its clinical benefit. Being able to detect MRD could give clinicians a more comprehensive view of the risk of relapse of their patients and could select patients requiring treatment escalation with the goal of improving cancer survival. In this review, we are discussing the different methodologies used and investigated to detect MRD in solid cancers, their respective potentials and issues, and the clinical impacts that MRD detection will have on the management of cancer patients.
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