Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
Department of General Surgery, West China Second Hospital, Sichuan University, Chengdu, China.
Platelets. 2024 Dec;35(1):2379815. doi: 10.1080/09537104.2024.2379815. Epub 2024 Jul 29.
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 × 10/L) and inferior OS (HR: 1.07; 95% CI: 1.04-1.10; < .001). Similar significant associations were observed for several cancer types. We further observed a U-shaped relationship between PLTs and cancer survival ( < .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; = .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.
先前的研究报告称血小板计数（PLT）与癌症生存之间的关联不一致。然而，是否存在线性因果效应值得深入研究。我们使用英国生物库进行了一项队列研究和两样本孟德尔随机化（MR）分析。PLT 水平在癌症诊断前进行测量。我们采用总生存（OS）作为主要结局。Cox 模型用于估计 PLT 对癌症诊断多个滞后时间的生存结局的影响。我们采用 34 个遗传变异作为 PLT 代理进行 MR 分析。模拟了线性和非线性效应。还研究了携带工具变量的基因表达的预后效应。共纳入 65471 例癌症患者。我们发现升高的 PLT（每 100×10/L）与较差的 OS 之间存在显著关联（HR：1.07；95%CI：1.04-1.10； < .001）。对于几种癌症类型，也观察到了类似的显著关联。我们进一步观察到 PLT 与癌症生存之间存在 U 形关系（ < .001）。我们的 MR 分析发现，没有证据支持 PLT 与整体癌症生存之间存在因果关系（HR：1.000；95%CI：0.998-1.001； = .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。十一个 PLT 相关基因的表达与癌症生存相关。早期发现 PLT 升高可能表明隐匿性癌症的发生和随后较差的生存结局。观察到的关联可能是非线性的。然而，PLT 不太可能成为有前途的治疗靶点。
