原发性肝癌患者血清前白蛋白与外周血淋巴细胞水平的关系

Relationship between serum prealbumin and peripheral blood lymphocyte levels in patients with primary liver cancer

目的 分析原发性肝癌(Primary liver cancer,PLC)患者血清前白蛋白(Prealbumin,PA)与临床指标、外周血淋巴细胞亚群水平变化的关系,为评估PLC患者的免疫状态提供新的思路。方法 选取2018年5月~2020年10月就诊于我院肝病科确诊为PLC的114例患者作为研究对象。按照血清PA检测值的四分位数将患者分为4组,分别为Q1组(PA≤1.49μmol/L,n=29)、Q2组(1.49μmol/L3.70μmol/L,n=27),比较患者临床指标(Child-Pugh分级、BCLC分期、肝肾功能、甲胎蛋白等)及外周免疫细胞(淋巴细胞、白细胞、中性粒细胞)水平的差异,采用线性回归模型分析PA与外周血淋巴细胞的相关性;收集各组患者外周血单个核细胞(Peripheral blood mononuclear cells,PBMCs)并进行RNA高通量测序,利用Cibersort估算淋巴细胞的丰度,进一步运用简单线性回归法分析PA与PBMCs中淋巴细胞群丰度的相关性。结果 在临床指标比较中,各组PA、Child-Pugh分级、BCLC分期、AFP、AFP-L3%、AST、GGT、TB、DB、TP、ALB、GLB、A/G、ALP、TBA、CHE、HBG差异具有统计学意义(P<0.05);在免疫细胞水平比较中,各组淋巴细胞水平差异具有统计学意义(P<0.05);线性回归分析结果显示,在调整AST、GGT、AFP及A/G水平后,PLC患者的PA水平与外周淋巴细胞数量呈正相关(调整后R2=0.12,β=0.38,P<0.05)。利用RNA-seq测序得到PBMCs中免疫细胞亚群丰度,发现PA与CD8+T细胞、静息记忆性CD4+T细胞、静息NK细胞呈正相关(调整后R2=0.06、0.16、0.05,β=0.26、0.41、0.23,P<0.05)。结论 PA是PLC患者外周血淋巴细胞水平变化的相关因素,且与CD8+T细胞、CD4+T细胞、NK细胞水平密切相关,可能成为PLC患者免疫状态的预测因子,为辅助选择治疗方案提供参考。

Objective To analyze the relationship between serum prealbumin (PA) and clinical indicators and changes of peripheral blood lymphocyte subpopulation levels in patients with primary liver cancer (PLC),provide new ideas for assessing the immune status of patients with PLC.Methods A total of 114 patients with confirmed PLC diagnosed in our hospital from May 2018 to Oct 2020 were selected as the study objects.Patients were divided into four groups according to the quartiles of serum PA test values:group Q1 (PA≤1.49μmol/L,n=29),group Q2 (1.49μmol/L3.70μmol/L,n=27),compared the difference of common clinical indicators (Child-Pugh score,BCLC,liver and kidney function,alpha fetoprotein,etc.) and peripheral immune cell (lymphocytes,leukocytes,neutrophils) levels in patients with PLC among the groups and analyzed the correlation between PA and peripheral blood lymphocytes using linear regression model.Collected peripheral blood mononuclear cells (PBMCs) from each group of patients and subjecting to RNA high-throughput sequencing,and the abundance of lymphocytes was estimated using Cibersort.Results In the comparison of clinical indicators among the groups,the differences in PA,Child-Pugh score,BCLC,AFP,AFP-L3%,AST,GGT,TB,DB,TP,ALB,GLB,A/G,ALP,TBA,CHE and HBG were statistically significant (P<0.05).In the comparison of immune cells,the difference in lymphocytes was statistically significant (P<0.05).Linear regression analysis showed a positive correlation between PA levels and peripheral lymphocyte counts in PLC patients after adjusting for AST,GGT,AFP and A/G levels (adjusted R~2=0.12,β=0.38,P<0.05).Immune cell population abundance in PBMCs was obtained using RNA-seq sequencing,and PA was found to be positively correlated with CD8+T cells (adjusted R~2=0.06,β=0.26,P<0.05),resting memory CD4+T cells (adjusted R~2=0.16,β=0.41,P<0.05),and resting NK cells (adjusted R~2=0.05,β=0.23,P<0.05).Conclusion PA is an influential factor in the changes of peripheral blood lymphocyte levels in PLC patients and is closely related to the levels of CD8+T cells,CD4+T cells,and NK cells.It may become a predictor of immune status in PLC patients and provide reference for the selection of treatment options for patients.