Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2605-10. doi: 10.1158/1055-9965.EPI-10-0178. Epub 2010 Aug 20.
Improved diagnostic, predictive, and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Platelet factor 4 (PF4) has been proposed as a diagnostic biomarker for PDAC. We assessed the diagnostic and prognostic potential of serum PF4 levels in PDAC patients.
Serum PF4 levels were determined by enzyme-linked immunosorbent assay in an initial cohort of 62 PDAC patients, 62 healthy control subjects, and 34 chronic pancreatitis patients. A second validation set consisted of 71 PDAC patients. Linear regression models were used to relate PF4 to class, gender, age, stage, platelet count, and diagnosis. Survival analyses were done using univariate and multivariate Cox models.
In the initial cohort, serum PF4 levels distinguished PDAC from chronic pancreatitis patients (P = 0.011), but not from healthy control subjects (P = 0.624). In PDAC patients, high serum PF4 level significantly predicted decreased survival independent of all covariates examined (P < 0.01). The prognostic relationship of serum PF4 levels remained significant in the validation set. Venous thromboembolism (VTE) occurred in 20% of the 133 PDAC patients. The VTE risk was higher in subjects with elevated PF4 levels (P = 0.009).
Serum PF4 is shown for the first time to be prognostic for survival in PDAC patients. High PF4 is associated with an increased risk for the development of VTE.
Serum PF4 levels may be useful for patient stratification and for directing treatment options in patients with pancreatic cancer including anticoagulation prophylaxis. The relationship between high PF4 levels and poorer outcomes requires further study.
迫切需要用于胰腺导管腺癌（PDAC）的改进的诊断、预测和预后生物标志物。血小板因子 4（PF4）已被提议作为 PDAC 的诊断生物标志物。我们评估了 PDAC 患者血清 PF4 水平的诊断和预后潜力。
通过酶联免疫吸附试验在 62 名 PDAC 患者、62 名健康对照者和 34 名慢性胰腺炎患者的初始队列中测定血清 PF4 水平。第二个验证队列由 71 名 PDAC 患者组成。线性回归模型用于将 PF4 与类别、性别、年龄、分期、血小板计数和诊断相关联。使用单变量和多变量 Cox 模型进行生存分析。
在初始队列中，血清 PF4 水平可区分 PDAC 与慢性胰腺炎患者（P = 0.011），但不能区分健康对照者（P = 0.624）。在 PDAC 患者中，高血清 PF4 水平显著预测独立于所有检查的协变量的生存下降（P < 0.01）。在验证队列中，血清 PF4 水平的预后关系仍然显著。133 名 PDAC 患者中有 20%发生静脉血栓栓塞（VTE）。PF4 水平升高的患者 VTE 风险更高（P = 0.009）。
血清 PF4 首次显示对 PDAC 患者的生存具有预后意义。高水平的 PF4 与发生 VTE 的风险增加相关。
血清 PF4 水平可能对患者分层有用，并为包括抗凝预防在内的胰腺癌患者提供治疗选择。高水平的 PF4 与较差的结果之间的关系需要进一步研究。
