外周血sPD-1及LAG-3表达与非小细胞肺癌预后的关系研究
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摘要
目的分析外周血可溶性程序性死亡受体1(sPD-1)和可溶性淋巴细胞活化基因-3(sLAG-3)是否可作为非小细胞肺癌预后评价指标。方法比较2017年12月至2018年2月该院收治的非小细胞肺癌患者53例(肺癌组)与健康体检者53例(健康对照组)外周血sPD-1和sLAG-3差异及与肿瘤标志物的相互关系,了解sPD-1和sLAG-3与非小细胞肺癌可能关系;并进一步通过COX回归分析sPD-1和sLAG-3与非小细胞肺癌生存率的关系及作为发生、发展预测指标的可能性。结果与健康对照组比较,肺癌组患者血清清蛋白和血清转铁蛋白出现降低,淋巴细胞绝对数升高,差异均有统计学意义(P<0.05);sPD-1和sLAG-3水平出现明显降低,肿瘤标志物癌胚抗原、CA199、CA125水平均出现升高,差异均有统计学意义(P<0.05)。相关性分析发现,sPD-1与CA199呈负相关(P=0.005),而sLAG-3与CA125趋向于负相关(P=0.051)。COX回归生存分析发现,肺癌组的生存率随sPD-1水平升高而增加(P=0.045),而与sLAG-3水平无关。结论监测sPD-1水平变化对了解非小细胞肺癌的发生、发展可能具有参考意义。
Objective To determine whether sPD-1 and sLAG-3 in peripheral blood can be used as the prognosis marker of NSCLC.Methods The differences of peripheral blood sPD-1 and sLAG-3,the relationship between sPD-1,sLAG-3 and tumor markers were compared between the lung cancer group(n=53)and the healthy control group(n=53),which all admitted to the hospital from December 2017 to February 2018,to learn the possible relationship between sPD-1,sLAG-3 and NSCLC.The relationship between sPD 1,sLAG-3 and survival rate of NSCLC,the possibility of using sPD-1 and sLAG-3 as prediction indicators for development were analyzed with COX regression.Results Compared with the healthy control group,serum albumin and serum transferrin of lung cancer group were decreased in NSCLC,the absolute number of lymphocytes increased,and the differences were statistically significant(P<0.05).The sPD-1 and sLAG-3 levels of lung cancer group were significantly reduced,carcinoembryonic antigen,CA199 and CA125,tumor markers were increased,and the differences were statistically significant(P<0.05).The correlation analysis showed that sPD-1 was negatively correlated with CA199(P=0.005),and sLAG-3 was negatively correlated with CA125(P=0.051).COX regression analysis showed that the survival rate increased with the growth of sPD-1(P=0.045),and was not associated with sLAG-3.Conclusion Monitoring the change of sPD-1 level may have reference significance for understanding the occurrence and development of NSCLC.
Objective To determine whether sPD-1 and sLAG-3 in peripheral blood can be used as the prognosis marker of NSCLC.Methods The differences of peripheral blood sPD-1 and sLAG-3,the relationship between sPD-1,sLAG-3 and tumor markers were compared between the lung cancer group(n=53)and the healthy control group(n=53),which all admitted to the hospital from December 2017 to February 2018,to learn the possible relationship between sPD-1,sLAG-3 and NSCLC.The relationship between sPD 1,sLAG-3 and survival rate of NSCLC,the possibility of using sPD-1 and sLAG-3 as prediction indicators for development were analyzed with COX regression.Results Compared with the healthy control group,serum albumin and serum transferrin of lung cancer group were decreased in NSCLC,the absolute number of lymphocytes increased,and the differences were statistically significant(P<0.05).The sPD-1 and sLAG-3 levels of lung cancer group were significantly reduced,carcinoembryonic antigen,CA199 and CA125,tumor markers were increased,and the differences were statistically significant(P<0.05).The correlation analysis showed that sPD-1 was negatively correlated with CA199(P=0.005),and sLAG-3 was negatively correlated with CA125(P=0.051).COX regression analysis showed that the survival rate increased with the growth of sPD-1(P=0.045),and was not associated with sLAG-3.Conclusion Monitoring the change of sPD-1 level may have reference significance for understanding the occurrence and development of NSCLC.
引文
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[11]李江斌,张红梅,王爽,等.可溶性人PD-1蛋白(shPD-1)对肿瘤患者树突状细胞功能的影响[J].实用癌症杂志,2010,25(1):1-4.
[2] HE Y,YU H,ROZEBOOM L,et al.LAG-3protein expression in non-small cell lung cancer and its relationship with PD-1/PD-L1and tumor-infiltrating lymphocytes[J].J Thorac Oncol,2017,12(5):814-823.
[3] WAN B,NIE H,LIU A,et al.Aberrant regulation of synovial T cell activation by soluble costimulatory molecules in rheumatoid arthritis[J].J Immunol,2006,177(12):8844-8850.
[4] GENG H,ZHANG GM,XIAO H,et al.HSP70vaccine in combination with gene therapy with plasmid DNA encoding sPD-1overcomes immune resistance and suppresses the progression of pulmonary metastatic melanoma[J].Int J Cancer,2006,118(11):2657-2664.
[5]杨振强.sB7-H3,CEA和CYFRA21-1联检对肺癌的诊断价值[J].放射免疫学杂志,2013,26(1):65-68.
[6] MOLINA R,AUGE JM,FILELLA X,et al.Pro-gastrin-releasing peptide(proGRP)in patients with benign and malignant diseases:comparison with CEA,SCC,CYFRA 21[J].Anticancer Res,2005,25(3A):1773-1778.
[7] TAKAHASHI H,KURISHIMA K,ISHIKAWA H,et al.Optimal cutoff points of CYFRA21-1for survival prediction in non-small cell lung cancer patients based on running statistical analysis[J].Anticancer Res,2010,30(9):3833-3837.
[8] MOLINA R,AUGE JM,ESCUDERO JM,et al.Mucins CA 125,CA 19.9,CA 15.3and TAG-72.3as tumor markers in patients with lung cancer:comparison with CYFRA 21-1,CEA,SCC and NSE[J].Tumour Biol,2008,29(6):371-380.
[9]张毅敏,夏文进.肺癌患者血清CA125水平与肺癌转移的关系分析[J].浙江医学,2009,31(5):599-601.
[10]王小红,张桂梅,贺宇飞,等.可溶性PD-1协同HSP70-肽复合物抑制荷瘤小鼠肝癌的研究[J].细胞与分子免疫学杂志,2004,20(6):655-658.
[11]李江斌,张红梅,王爽,等.可溶性人PD-1蛋白(shPD-1)对肿瘤患者树突状细胞功能的影响[J].实用癌症杂志,2010,25(1):1-4.