Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Cancer Sci. 2012 Sep;103(9):1714-21. doi: 10.1111/j.1349-7006.2012.02358.x. Epub 2012 Jul 30.
Extracellular high mobility group box-1 (HMGB1) contributes to tumor growth and invasiveness. We evaluated the diagnostic and prognostic ability of serum HMGB1 for pancreatic ductal adenocarcinoma (PDAC). Serum HMGB1 measured by enzyme-linked immunosorbent assay (ELISA) were compared among normal, chronic pancreatitis, PDAC group in both training (n = 25, each group) and independent validation set (n = 45, each group). To determine the usability of serum HMGB1 as a diagnostic predictor of PDAC, receiver operating characteristic (ROC) curves with sensitivity/specificity and logistic regression were evaluated. To assess the HMGB1-associated prognosis of PDAC, Kaplan-Meier survival and Cox proportional-hazards regression were applied. Serum HMGB1 was correlated with presence and advanced-stage of PDAC. Logistic regression exhibited serum HMGB1 was a remarkable biomarker to predict PDAC as a single or multiple-markers; sensitivity/specificity of serum HMGB1 were superior to carbohydrate antigen (CA) 19-9 or carcinoembryonic antigen (CEA) in both training and independent datasets. Kaplan-Meier survival analysis showed PDAC patients with high serum HMGB1 levels (>30 ng/mL; median survival, 192 days) had a worse prognosis than patients with low HMGB1 levels (≤30 ng/mL; 514 days) by log-rank (P = 0.017). Cox proportional-hazards model showed the relative hazard ratios in high-serum HMGB1 group was 3.077 compared with the low-serum HMGB1 group. In conclusion, serum HMGB1 is a desirable diagnostic and prognostic biomarker for PDAC compared with pre-existing PDAC biomarkers, CA19-9 and CEA.
细胞外高迁移率族蛋白 B1 (HMGB1) 有助于肿瘤的生长和侵袭。我们评估了血清 HMGB1 对胰腺导管腺癌 (PDAC) 的诊断和预后能力。通过酶联免疫吸附测定 (ELISA) 比较了正常、慢性胰腺炎和 PDAC 组患者血清 HMGB1 的水平,其中训练集 (n = 25,每组) 和独立验证集 (n = 45,每组) 中均有患者纳入。为了确定血清 HMGB1 作为 PDAC 诊断预测因子的可用性,评估了敏感性/特异性和逻辑回归的受试者工作特征 (ROC) 曲线。为了评估 HMGB1 与 PDAC 预后的相关性,应用了 Kaplan-Meier 生存分析和 Cox 比例风险回归。结果显示血清 HMGB1 与 PDAC 的存在和晚期有关。逻辑回归表明,血清 HMGB1 是预测 PDAC 的一个显著生物标志物,无论是作为单一标志物还是多个标志物;在训练集和独立数据集,血清 HMGB1 的敏感性/特异性均优于癌抗原 19-9 (CA19-9) 或癌胚抗原 (CEA)。Kaplan-Meier 生存分析显示,血清 HMGB1 水平较高 (>30ng/ml;中位生存时间 192 天) 的 PDAC 患者的预后较 HMGB1 水平较低 (≤30ng/ml;514 天) 的患者差 (log-rank,P = 0.017)。Cox 比例风险模型显示,高血清 HMGB1 组的相对危险比为 3.077,与低血清 HMGB1 组相比。总之,与现有的 PDAC 标志物 CA19-9 和 CEA 相比,血清 HMGB1 是 PDAC 理想的诊断和预后生物标志物。