He Yongqiao, Yang Dawei, Zhou Ting, Xue Wenqiong, Zhang Jiangbo, Li Fangfang, Wang Fang, Wang Tongmin, Wu Ziyi, Liao Ying, Zheng Meiqi, Deng Changmi, Li Danhua, Jia Yijing, Yuan Leilei, Zhang Wenli, Jia Weihua
Department of Radiation Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510030, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510030, China.
Cancer Biol Med. 2021 May 7;18(3):888-99. doi: 10.20892/j.issn.2095-3941.2020.0464.
Circulating cell-free Epstein-Barr virus (EBV) DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma (NPC). Despite important insights into the biology of persistence, few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells (PBCs).
A prospective observational cohort study was conducted involving 1,063 newly diagnosed, locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007. Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival (OS) and other prognostic outcomes. Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.
After a median follow-up of 108 months, patients with higher PBC EBV-DNA loads had significantly worse OS [hazard ratio (HR) of medium, medium-high, and high low were 1.50, 1.52, and 1.85 respectively; < 0.001]. Similar results were found for progression-free survival and distant metastasis-free survival. The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66, respectively. Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker, which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort (HR: 1.88; = 0.025). Importantly, a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.
The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.
循环游离 Epstein-Barr 病毒(EBV)DNA 已被证明是鼻咽癌(NPC)人群筛查和预后监测的重要生物标志物。尽管对病毒持续存在的生物学机制有了重要认识,但很少有研究探讨外周血细胞(PBC)中基于细胞的 EBV-DNA 载量的临床意义。
对 2005 年至 2007 年在中山大学肿瘤防治中心新诊断的 1063 例局部区域晚期 NPC 患者进行了一项前瞻性观察队列研究。采用 Cox 回归分析确定 PBC EBV DNA 载量与总生存期(OS)及其他预后指标的相关性。基于 PBC EBV DNA 载量制定预后列线图,以预测 NPC 患者的生存结局。
中位随访 108 个月后,PBC EBV-DNA 载量较高的患者 OS 显著较差[中、中高、高与低载量组的风险比(HR)分别为 1.50、1.52 和 1.85;P<0.001]。无进展生存期和无远处转移生存期也得到类似结果。训练集和验证集中预测 OS 的预后列线图的一致性指数分别为 0.70 和 0.66。我们的数据表明,PBC EBV DNA 载量是一个独立且可靠的生存生物标志物,在该队列 205 例患者的亚组中,即使在调整血浆 EBV DNA 载量后仍具有显著性(HR:1.88;P = 0.025)。重要的是,PBC EBV DNA 载量与血浆 EBV DNA 载量相结合可改善对 OS 的预测。
PBC 中的 EBV-DNA 载量可能是 NPC 患者的独立预后标志物。