评估诊断前血小板计数与癌症生存结果之间的非线性关联:观察和遗传分析。

IF 2.5 3区 医学 Q3 CELL BIOLOGY
Platelets Pub Date : 2024-12-01 Epub Date: 2024-07-29 DOI:10.1080/09537104.2024.2379815
Changtao Li, Junhua Chen, Deqian Han, Chi Shu, Jun Huang, Linru Wei, Haoran Luo, Qingbin Wu, Xin Chen, Yazhou He, Yanhong Zhou
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引用次数: 0

摘要

以往的研究报告显示,血小板计数(PLT)与癌症生存率之间的关系并不一致。然而,是否存在线性因果效应值得深入研究。我们利用英国生物库和双样本孟德尔随机化(MR)分析进行了一项队列研究。PLT水平是在癌症诊断前测定的。我们将总生存期(OS)作为主要结果。我们利用 Cox 模型来估算癌症诊断的多个滞后时间内 PLT 对生存结果的影响。在 MR 分析中,我们采用了 34 个基因变异作为 PLT 代用指标。对线性和非线性效应进行了建模。我们还研究了携带工具变异的基因表达对预后的影响。共纳入 65 471 名癌症患者。我们发现 PLT 升高(每 100 × 109/L)与较差的 OS 之间存在明显关联(HR:1.07;95% CI:1.04-1.10;p p p = .678),尽管非线性 MR 分析揭示了在较低 PLT 范围内可能存在更大的不利影响。11 个 PLT 相关基因的表达与癌症生存率相关。PLT 升高的早期检测表明可能存在隐匿性癌症发展和较差的后续生存结果。观察到的关联可能是非线性的。不过,PLT不太可能成为有希望的治疗目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Appraising non-linear association between pre-diagnostic platelet counts and cancer survival outcomes: observational and genetic analysis.

Previous studies have reported inconsistent associations between platelet count (PLT) and cancer survival. However, whether there is linear causal effect merits in-depth investigations. We conducted a cohort study using the UK Biobank and a two-sample Mendelian randomization (MR) analysis. PLT levels were measured prior to cancer diagnosis. We adopted overall survival (OS) as the primary outcome. Cox models were utilized to estimate the effects of PLTs on survival outcomes at multiple lag times for cancer diagnosis. We employed 34 genetic variants as PLT proxies for MR analysis. Linear and non-linear effects were modeled. Prognostic effects of gene expression harboring the instrumental variants were also investigated. A total of 65 471 cancer patients were included. We identified a significant association between elevated PLTs (per 100 × 109/L) and inferior OS (HR: 1.07; 95% CI: 1.04-1.10; p < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival (p < .001). Our MR analysis found null evidence to support a causal association between PLTs and overall cancer survival (HR: 1.000; 95% CI: 0.998-1.001; p = .678), although non-linear MR analysis unveiled a potential greater detrimental effect at lower PLT range. Expression of eleven PLT-related genes were associated with cancer survival. Early detection of escalated PLTs indicated possible occult cancer development and inferior subsequent survival outcomes. The observed associations could potentially be non-linear. However, PLT is less likely to be a promising therapeutic target.

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来源期刊
Platelets
Platelets 医学-细胞生物学
CiteScore
6.70
自引率
3.00%
发文量
79
审稿时长
1 months
期刊介绍: Platelets is an international, peer-reviewed journal covering all aspects of platelet- and megakaryocyte-related research. Platelets provides the opportunity for contributors and readers across scientific disciplines to engage with new information about blood platelets. The journal’s Methods section aims to improve standardization between laboratories and to help researchers replicate difficult methods. Research areas include: Platelet function Biochemistry Signal transduction Pharmacology and therapeutics Interaction with other cells in the blood vessel wall The contribution of platelets and platelet-derived products to health and disease The journal publishes original articles, fast-track articles, review articles, systematic reviews, methods papers, short communications, case reports, opinion articles, commentaries, gene of the issue, and letters to the editor. Platelets operates a single-blind peer review policy. Authors can choose to publish gold open access in this journal.
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