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预测 10 年全因和疾病特异性死亡率的生物标志物特征。

Biomarker Signatures Predicting 10-Year All-Cause and Disease-Specific Mortality.

机构信息

Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis, Singapore.

Institute of Ageing and Chronic Disease, University of Liverpool, UK.

出版信息

J Gerontol A Biol Sci Med Sci. 2019 Mar 14;74(4):469-479. doi: 10.1093/gerona/gly138.

Abstract

Novel wide array blood biomarkers of multisystem dysregulation, compared to conventional clinical and blood biomarkers, are potentially able to provide more accurate prognostic information of long-term mortality risks. We identified biomarker signatures of all-cause and disease-specific mortality from a comprehensive range of analytes related to six major physiological functions: cytokine, chemokine, and growth factors; glucose metabolism regulators and adipokines; adhesion molecules; acute phase response; pathogen-specific antibodies; and bone remodeling. A total of 144 elderly were prospectively followed up on mortality for median 136 months. Plasma levels of 93 biomarkers measured by enzyme-linked immunosorbent assay, Luminex, FlowCytomix, DNA quantification, and recombinant DNA technology at baseline were compared among deceased and surviving elderly and in a referent group of 72 healthy young adults. The elderly, and especially deceased elderly, exhibited differential profiles of the composite index of each physiological function from young adults. In Cox regression, we identified and validated in an independent cohort of 357 elderly the specific and common biomarkers predicting all-cause, cardiovascular disease-related, neoplasm-related, and respiratory disease-related mortalities after controlling age, sex, and major comorbidities. These biomarkers had 74.3% correct classification for deceased elderly from surviving elderly. We reported for the first time, stem cell growth factor-β and gastric inhibitory polypeptide as specific biomarkers of mortality risk.

摘要

与传统的临床和血液生物标志物相比,新型广泛的多系统失调血液生物标志物可能能够提供更准确的长期死亡率风险的预后信息。我们从与六大生理功能相关的各种分析物中确定了全因和特定疾病死亡率的生物标志物特征:细胞因子、趋化因子和生长因子;葡萄糖代谢调节剂和脂肪因子;黏附分子;急性期反应;病原体特异性抗体;和骨重塑。共有 144 名老年人前瞻性地进行了中位随访 136 个月的死亡率随访。通过酶联免疫吸附试验、Luminex、FlowCytomix、DNA 定量和重组 DNA 技术测量的 93 种生物标志物的血浆水平在基线时在已故和存活的老年人以及 72 名健康年轻成年人的参考组中进行了比较。老年人,尤其是已故老年人,与年轻人相比,表现出每种生理功能综合指数的不同特征。在 Cox 回归中,我们在一个独立的 357 名老年人队列中进行了鉴定和验证,这些标志物在控制年龄、性别和主要合并症后可以预测全因、心血管疾病相关、肿瘤相关和呼吸疾病相关的死亡率。这些标志物能够正确分类 74.3%的已故老年人和存活的老年人。我们首次报道了干细胞生长因子-β和胃抑制肽作为死亡率风险的特异性生物标志物。

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