循环 APRIL 水平与直肠癌患者的疾病进展和预后相关。

Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

作者信息

Lascano V, Hahne M, Papon L, Cameron K, Röeder C, Schafmayer C, Driessen L, van Eenennaam H, Kalthoff H, Medema J P

机构信息

LEXOR (Lab of Experimental Oncology and Radiobiology), Center for Experimental Molecular Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands.

1] LEXOR (Lab of Experimental Oncology and Radiobiology), Center for Experimental Molecular Medicine, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, The Netherlands [2] Institut de Génétique Moléculaire (IGMM), CNRS UMR5535, Montpellier, France [3] Université Montpellier Sud de France, Montpellier, France.

出版信息

Oncogenesis. 2015 Jan 26;4(1):e136. doi: 10.1038/oncsis.2014.50.

DOI:10.1038/oncsis.2014.50

PMID:25622308

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5520648/

Abstract

We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan-Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16-2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79-1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression.

摘要

我们之前已经表明，肿瘤坏死因子家族成员增殖诱导配体（APRIL）在多种临床前肿瘤模型中可促进肠道肿瘤生长。在此，我们研究了手术时APRIL血清水平是否可预测一大群结直肠癌（CRC）患者的生存率。我们使用一种经过验证的新型单克隆APRIL抗体（hAPRIL.133），通过酶联免疫吸附测定（ELISA）方法，检测了一组CRC患者（n = 432）的循环APRIL水平。APRIL水平与临床病理特征及预后相关。采用Kaplan-Meier生存分析检查总生存率，并计算Cox比例风险比。我们观察到，CRC患者的循环APRIL水平呈正态分布。APRIL高表达与不良预后指标显著相关，如就诊时分期较高以及出现淋巴和远处转移。在直肠癌患者组中，手术时较高的循环APRIL水平与较差的生存率相关（对数秩分析P值为0.008）。对直肠癌患者总生存率的单因素Cox回归分析表明，循环APRIL水平升高的患者预后不良风险增加（风险比（HR）为1.79；95%置信区间（CI）为1.16 - 2.76；P值为0.009）。对直肠癌患者的多因素分析表明，APRIL作为预后因素取决于疾病分期（HR为1.25；95%CI为0.79 - 1.99；P值为0.340），这与IV期直肠癌患者的APRIL水平显著较高这一事实相关。我们的结果显示，手术时APRIL血清水平与直肠癌患者的晚期疾病特征和预后相关，这强化了之前报道的APRIL水平升高与疾病进展相关的临床前观察结果。