Departments of Medicine, Columbia University, New York, New York, USA.
Department of Epidemiology, Columbia University, New York, New York, USA.
Clin Transl Gastroenterol. 2015 Feb 5;6(2):e74. doi: 10.1038/ctg.2014.22.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. CA19-9 is a glycoprotein that predicts poor prognosis in pancreatic and biliary malignancies. We evaluated it as a prognostic biomarker for patients with HCC.
We prospectively enrolled 145 patients with HCC, diagnosed using American Association for Study of Liver Diseases criteria, between October 2008 and November 2012. We examined whether baseline serum CA19-9 levels predicted overall survival. We also examined immunostains of hepatic resections and explants of patients with elevated and normal serum CA19-9.
In a cohort of predominantly hepatitis C and B patients, CA19-9 ≥100 U/ml was associated with a 2.7-fold increased mortality (hazard ratio (HR): 2.72; 95% confidence interval (CI): 1.52-4.88, P<0.001). It remained a significant predictor (HR: 2.58; 95% CI: 1.41-4.72, P=0.002) in a multivariable model adjusted for Child-Pugh score, alpha-fetoprotein, Barcelona Clinic Liver Cancer stage, and Model for End-Stage Liver Disease. CA19-9 immunohistochemistry performed on a subset of liver resection and explant specimens showed increased CA19-9 immunostaining of non-tumor liver parenchyma in patients with elevated serum CA19-9. It also showed staining of native and reactive bile ducts, and of progenitor-like cells at the periphery of cirrhotic nodules.
Elevated serum CA19-9 ≥100 U/ml is an independent predictor of poor overall survival in this hypothesis-generating study. The unfavorable prognosis seen with elevated serum levels may be related to progenitor-like cells in the non-tumor liver.
肝细胞癌（HCC）是全球癌症相关死亡的第三大原因。CA19-9 是一种糖蛋白，可预测胰腺和胆道恶性肿瘤的预后不良。我们评估了其作为 HCC 患者预后生物标志物的作用。
我们前瞻性纳入了 2008 年 10 月至 2012 年 11 月期间根据美国肝病研究协会标准诊断为 HCC 的 145 例患者。我们检查了基线血清 CA19-9 水平是否预测总生存期。我们还检查了血清 CA19-9 升高和正常的患者肝切除和肝移植标本的免疫组化染色。
在主要为丙型和乙型肝炎患者的队列中，CA19-9≥100U/ml 与死亡率增加 2.7 倍相关（风险比（HR）：2.72；95%置信区间（CI）：1.52-4.88，P<0.001）。在调整了 Child-Pugh 评分、甲胎蛋白、巴塞罗那临床肝癌分期和终末期肝病模型后，它仍然是一个显著的预测因子（HR：2.58；95%CI：1.41-4.72，P=0.002）。对部分肝切除和肝移植标本进行 CA19-9 免疫组化染色显示，血清 CA19-9 升高的患者非肿瘤肝实质中 CA19-9 免疫染色增加。它还显示了固有和反应性胆管以及肝硬化结节边缘祖细胞样细胞的染色。
在这项假设生成研究中，血清 CA19-9 升高≥100U/ml 是总生存期不良的独立预测因子。血清水平升高与非肿瘤肝中的祖细胞样细胞有关，预后不良。
