鼻咽癌患者免疫功能状态与EBV DNA的相关性及对预后的影响

魏雪玲; 兰美; 彭新皓; 张菡奕; 龙恩; 刘会; 郎锦义

doi:10.3971/j.issn.1000-8578.2021.20.1402

鼻咽癌患者免疫功能状态与EBV DNA的相关性及对预后的影响

Correlation Between Immune Function Status and EBV DNA in Patients with Nasopharyngeal Carcinoma and Their Influence on Prognosis

摘要

摘要:
目的探讨鼻咽癌(NPC)患者治疗前EB病毒(EBV)DNA载量与外周血淋巴细胞亚群及NK细胞的相关性，并进一步分析与EBV相关的循环免疫细胞亚群对鼻咽癌患者预后的影响。
方法收集203例初治无远处转移鼻咽癌患者的一般资料及外周血EBV DNA和循环免疫细胞亚群等数据。采用MedCalc统计软件中ROC曲线分析确定各循环免疫细胞亚群截断值。Kaplan-Meier法进行生存分析，Cox回归模型进行多因素预后相关分析。
结果 EBV DNA < 400 copies/ml组和EBV DNA≥400 copies/ml组的3年OS、PFS、DMFS和LRFS分别为99.2% vs. 90.1%(P=0.001)、96.7% vs. 90.1%(P=0.028)、98.4% vs. 90.1%(P=0.005)和98.4% vs. 100%(P > 0.05)。患者治疗前EBV DNA与CD19⁺B细胞比例呈负相关(r=-0.138, P=0.040)，与其他循环免疫细胞无明显相关性(均P > 0.05)。ROC分析显示治疗前CD19⁺B细胞比例与OS相关的Cut-off值为8.33%。治疗前CD19⁺B细胞比例≤8.33% > 8.33%患者的3年OS、PFS、DMFS和LRFS分别为90.4% vs. 99.2%(P=0.003)、89.2% vs. 97.5%(P=0.008)、90.4% vs. 98.3%(P=0.008)和98.8% vs. 99.2%(P > 0.05)。然而，ROC分析显示，其他外周免疫细胞(包括CD3⁺T、CD3⁺CD4⁺T、CD3⁺CD8⁺T和CD56⁺NK细胞的比例以及CD4⁺/CD8⁺比值)与OS没有显著相关性。多因素分析显示EBV DNA载量是NPC患者3年PFS的独立预后影响因素，CD19⁺B细胞比例是NPC患者3年PFS、DMFS、OS的独立预后因素。
结论治疗前血浆EBV DNA与外周血中CD19⁺B细胞比例存在负相关；两者可作为NPC 3年OS、PFS和DMFS的预测指标。

Abstract:
Objective To explore the correlation between EBV DNA load and peripheral immune cells (including lymphocyte supsets and natural killer cells) before treatment in patients with NPC, and analyze the influence of circulating immune cell supsets related to EBV on the prognosis of NPC patients.
Methods We retrospectively analyzed the general data of 203 NPC patients without distant metastasis at the first treatment, as well as the data of peripheral blood EBV DNA and circulating immune cell supset. The ROC curve analysis was used to determine the cutoff value of each circulating immune cell supset. Kaplan-Meier method was used for survival analysis, and Cox regression model was used for multi-factor prognostic correlation analysis.
Results The 3-year OS, PFS, DMFS and LRFS of EBV DNA < 400 copies/ml group and EBV DNA≥400 copies/ml group were 99.2% vs. 90.1% (P=0.001), 96.7% vs. 90.1% (P=0.028), 98.4% vs. 90.1% (P=0.005) and 98.4% vs. 100% (P > 0.05), respectively. EBV DNA is negatively correlated with the ratio of CD19⁺ B cells before treatment (r=-0.138, P=0.040), and there was no significant correlation between EBV DNA and other circulating immune supgroups (P > 0.05). ROC analysis showed that the cut-off value of CD19⁺B cell ratio before treatment related to the 3-year OS was 8.33% (P=0.02). The 3-year OS, PFS, DMFS and LRFS of patients with CD19⁺B cells ratio ≤8.33% and CD19⁺B cells ratio > 8.33% were respectively 90.4% vs. 99.2% (P=0.003), 89.2% vs. 97.5% (P=0.008), 90.4% vs. 98.3% (P=0.008) and 98.8% vs. 99.2% (P > 0.05). However, ROC analysis showed that there was no significant correlation between OS and other peripheral immune cells (including the proportion of CD3⁺T, CD3⁺CD4⁺T, CD3⁺CD8⁺T and CD56⁺NK cells and CD4⁺/CD8⁺ ratio). Multivariate analysis showed that EBV DNA load was an independent prognostic factor of 3-year PFS of NPC patients, and the ratio of CD19⁺B cells was an independent prognostic factor of 3-year PFS, MFS and OS of NPC patients.
Conclusion Before treatment, there is a negative correlation between plasma EBV DNA and the proportion of CD19⁺B cells in peripheral blood. Both can be used as the predictors of 3-year OS, PFS and DMFS of NPC patients.

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