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全血 DNA 甲基化衰老标志物可预测结直肠癌的生存:一项前瞻性队列研究。

Whole blood DNA methylation aging markers predict colorectal cancer survival: a prospective cohort study.

机构信息

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.

German Cancer Consortium, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120, Heidelberg, Germany.

出版信息

Clin Epigenetics. 2020 Nov 30;12(1):184. doi: 10.1186/s13148-020-00977-4.


DOI:10.1186/s13148-020-00977-4
PMID:33256852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7708179/
Abstract

BACKGROUND: Blood DNA methylation-based aging algorithms predict mortality in the general population. We investigated the prognostic value of five established DNA methylation aging algorithms for patients with colorectal cancer (CRC). METHODS: AgeAccelHorvath, AgeAccelHannum, DNAmMRscore, AgeAccelPheno and AgeAccelGrim were constructed using whole blood epi-genomic data from 2206 CRC patients. After a median follow-up of 6.2 years, 1079 deaths were documented, including 596 from CRC. Associations of the aging algorithms with survival outcomes were evaluated using the Cox regression and survival curves. Harrell's C-statistics were computed to investigate predictive performance. RESULTS: Adjusted hazard ratios (95% confidence intervals) of all-cause mortality for patients in the third compared to the first tertile were 1.66 (1.32, 2.09) for the DNAmMRscore, 1.35 (1.14, 1.59) for AgeAccelPheno and 1.65 (1.37, 2.00) for AgeAccelGrim, even after adjustment for age, sex and stage. AgeAccelHorvath and AgeAccelHannum were not associated with all-cause or CRC-specific mortality. In stage-specific analyses, associations were much stronger for patients with early or intermediate stage cancers (stages I, II and III) than for patients with metastatic (stage IV) cancers. Associations were weaker and less often statistically significant for CRC-specific mortality. Adding DNAmMRscore, AgeAccelPheno or AgeAccelGrim to models including age, sex and tumor stage improved predictive performance moderately. CONCLUSIONS: DNAmMRscore, AgeAccelPheno and AgeAccelGrim could serve as non-invasive CRC prognostic biomarkers independent of other commonly used markers. Further research should aim for tailoring and refining such algorithms for CRC patients and to explore their value for enhanced prediction of treatment success and treatment decisions.

摘要

背景:基于血液 DNA 甲基化的衰老算法可预测普通人群的死亡率。我们研究了五个已建立的用于结直肠癌(CRC)患者的 DNA 甲基化衰老算法的预后价值。

方法:使用来自 2206 例 CRC 患者的全血表观基因组数据构建了 AgeAccelHorvath、AgeAccelHannum、DNAmMRscore、AgeAccelPheno 和 AgeAccelGrim。中位随访 6.2 年后,记录了 1079 例死亡,其中 596 例死于 CRC。使用 Cox 回归和生存曲线评估衰老算法与生存结局的关联。计算 Harrell 的 C 统计量以研究预测性能。

结果:与第一 tertile 相比,所有原因死亡率的调整后危险比(95%置信区间)为 DNAmMRscore 的 1.66(1.32,2.09)、AgeAccelPheno 的 1.35(1.14,1.59)和 AgeAccelGrim 的 1.65(1.37,2.00),即使在调整年龄、性别和分期后也是如此。AgeAccelHorvath 和 AgeAccelHannum 与所有原因或 CRC 特异性死亡率无关。在分期特异性分析中,早期或中期癌症(I、II 和 III 期)患者的相关性要强得多,而转移性(IV 期)癌症患者的相关性较弱且往往不具有统计学意义。对于 CRC 特异性死亡率,相关性较弱且往往不具有统计学意义。将 DNAmMRscore、AgeAccelPheno 或 AgeAccelGrim 添加到包含年龄、性别和肿瘤分期的模型中,可以适度改善预测性能。

结论:DNAmMRscore、AgeAccelPheno 和 AgeAccelGrim 可作为独立于其他常用标志物的非侵入性 CRC 预后生物标志物。进一步的研究应旨在为 CRC 患者定制和改进此类算法,并探索其在增强治疗成功和治疗决策预测方面的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/f7ac1f96e5a4/13148_2020_977_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/f00823455a43/13148_2020_977_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/7eb8a83a9951/13148_2020_977_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/f7ac1f96e5a4/13148_2020_977_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/f00823455a43/13148_2020_977_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/7eb8a83a9951/13148_2020_977_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d5/7708179/f7ac1f96e5a4/13148_2020_977_Fig3_HTML.jpg

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[6]
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[7]
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[8]
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Cancers (Basel). 2022-2-17

[9]
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[10]
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本文引用的文献

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