肝癌患者PD-1表达及其与预后关系的Meta分析

PD-1 expression in patients with hepatocellular carcinoma and its relationship with clinical prognosis: a Meta-analysis

目的:探讨肝细胞癌(肝癌)患者血清可溶性PD-1(sPD-1)水平和癌组织PD-1表达及其与预后的关系。方法:本研究对象为2019年11月至2020年6月于内蒙古赤峰市医院行根治性切除术的21例肝癌患者。其中男15例,女6例;年龄40~81岁,中位年龄58岁。ELISA法检测血清sPD-1水平,免疫组化法检测癌组织PD-1表达。采用Spearman等级相关分析分析血清sPD-1水平、癌组织PD-1表达与肝癌患者临床病理参数间的关系。同时进一步检索中国知网(CNKI)、万方、中国生物医药数据库(CBM)、PubMed、Cochrane Library、Embase等数据库中关于血清sPD-1水平、癌组织PD-1表达与肝癌预后关系的文献,并进行Meta分析。结果:肝癌患者血清sPD-1水平中位数为1365(589~3315)ng/L。癌组织PD-1阳性率为95%(20/21),其中弱阳性表达11例,中度阳性表达9例。Spearman等级相关分析显示,肝癌患者术前血清sPD-1水平与癌组织PD-1表达强度成负相关(rs=-0.566,P<0.05);肝癌组织PD-1阳性表达强度与病理分化程度成负相关(rs=-0.513,P<0.05),而血清sPD-1水平与病理分化程度成正相关(rs=0.536,P<0.05)。Meta分析显示,PD-1高表达组和低表达组的总体生存期差异有统计学意义(HR=1.30,95%CI:1.02~1.65,P<0.05);而血清sPD-1水平与总体生存期无关(HR=0.95,95%CI:0.32~2.97,P>0.05)。结论:肝癌患者血清sPD-1水平与癌组织PD-1表达强度成负相关,且二者均与病理分化程度相关。肝癌组织PD-1表达程度高的患者预后较差。

Objective To investigate the serum level of soluble PD-1 (sPD-1) in hepatocellular carcinoma (HCC) patients and its relationship with the clinical prognosis.Methods21 patients with HCC underwent radical resection in Chifeng Municipal Hospital from November 2019 to June 2020 were enrolled. Among them, 15 patients were male and 6 female, aged from 40 to 81 years, with a median age of 58 years. Serum sPD-1 level was detected by ELISA, and the expression level of PD-1 in cancer tissues was determined by immunohistochemical staining. The relationship among serum sPD-1 level, PD-1 expression level in cancer tissues and clinicopathological parameters of HCC patients was assessed by Spearman rank correlation analysis. Literature search related to the relationship among serum sPD-1 level, PD-1 expression level in cancer tissues and clinical prognosis of HCC was conducted in CNKI, Wanfang Data, Chinese Biomedical Database (CBM), PubMed, Cochrane Library and Embase, and a Meta-analysis was carried out.ResultsThe median serum level of sPD-1 in HCC patients was 1 365 (589-3 315) ng/L. The positive rate of PD-1 in cancer tissues was 95% (20/21), including 11 cases of weakly positive expression and 9 cases of moderately positive expression. Spearman analysis showed that preoperative serum sPD-1 level was negatively correlated with the expression intensity of PD-1 in cancer tissues (rs=-0.566, P<0.05). The positive expression intensity of PD-1 in cancer tissues was negatively correlated with the pathological differentiation (rs=-0.513, P<0.05), whereas the serum level of sPD-1 was positively correlated with pathological differentiation (rs=0.536, P<0.05). Significant difference was observed in the overall survival between high and low PD-1 expression groups by Meta-analysis (HR=1.30, 95%CI: 1.02-1.65, P<0.05). The serum level of sPD-1 was not correlated with the overall survival (HR=0.95, 95%CI: 0.32-2.97, P>0.05).ConclusionsThe serum level ofsPD-1 in HCC patients is negatively correlated with the expression intensity of PD-1 in cancer tissues, and both of them are associated with the pathological differentiation. HCC patients with high expression of PD-1 in cancer tissues have poorer prognosis.