脑脊液中肺癌循环肿瘤标志物表达水平的影响因素分析

Analysis of factors influencing the expression levels of lung cancer circulating tumor markers in cerebrospinal fluid

目的:分析不同肺癌肿瘤标志物(tumor marker,TM)在脑脊液中正常表达水平,探讨血清TM水平、合并脑实质转移对其影响,从而更准确地判断可疑脑膜转移患者脑脊液TM是否升高。方法:收集2015年1月至2024年2月就诊于天津医科大学肿瘤医院80例无脑膜转移患者临床资料(非肺癌16例,肺癌64例),分析各TM在非肺癌患者脑脊液中正常的表达水平,以及脑脊液与血清中TM水平的差异;分析血清TM与脑脊液中TM水平的相关性;比较合并脑实质转移组与无脑实质转移组之间脑脊液中TM水平的差异。结果:组织多肽特异抗原(TPSA)、癌类抗原19-9 (CA19-9)、癌胚抗原(CEA)、细胞角蛋白19片段(Cyfra21-1)及鳞状细胞癌抗原(SCC)在脑脊液中的正常表达水平低于血清中水平(P<0.05),但胃泌素释放肽前体(ProGRP)、神经元特异烯化醇酶(NSE)在脑脊液中的表达水平高于血清中水平(P<0.05)。TPSA、SCC、ProGRP、NSE、CEA、CA199和Cyfra21-1在脑脊液中的水平与血清中的水平均无显著相关(均P>0.05)。与无脑实质转移患者相比,合并脑实质转移患者脑脊液中TPSA、SCC、ProGRP、CA19-9水平均无明显升高(P>0.05);CEA、Cyfra21-1虽然升高(P<0.05),但中位值升高不足2倍且均在参考值范围内,而NSE在合并脑实质转移组中的水平低于无脑实质转移组。结论:ProGRP及NSE在正常脑脊液中基础水平明显高于血清中的水平,其余肿瘤标志物在脑脊液中表达水平则明显低于血清中水平;血清中肿瘤标志物水平升高与否,以及是否合并脑实质转移并不会对脑脊液中肿瘤标志物水平产生具有临床意义的影响。

Objective:To analyze the normal expression levels of different lung cancer tumor markers(TM)in the cerebrospinal fluid and to explore the influence of serum TM levels and brain parenchymal metastasis,to more accurately determine whether the cerebrospinal fluid TM levels of patients with suspected meningeal metastasis is elevated.Methods:The clinical data of 80 patients diagnosed with non-lepto-meningeal metastasis at Tianjin Medical University Cancer Hospital between January 2015 and February 2024 were collected,including 16 patients without lung cancer and 64 patients with lung cancer.Normal TM levels in the cerebrospinal fluid of patients without lung cancer and the difference in TM levels between the cerebrospinal fluid and serum samples were analyzed.The correlation between serum and cerebrospinal fluid TM levels was also analyzed.We then compared the differences in TM levels in the cerebrospinal fluid between groups with brain parenchymal metastasis and without brain parenchymal metastasis.Results:Normal levels of TPSA,CA19-9,CEA,Cyfra21-1,and SCC in the cerebrospinal fluid were lower than those in the serum(P<0.05);however,the levels of ProGRP and NSE in the cerebrospinal fluid were higher than those in the serum(P<0.05).The levels of TPSA,SCC,ProGRP,NSE,CEA,CA19-9,and Cyfra21-1 in the cerebrospinal fluid did not correlate with those in the serum(all P>0.05).The cerebrospinal fluid levels of TPSA,SCC,ProGRP,and CA19-9 were not significantly increased in patients with brain parenchymal metastasis compared to those in patients without brain parenchymal metastasis(P>0.05).Al-though CEA and Cyfra21-1 levels increased(P<0.05),their median values increased by less than 2 times and were all within the reference range;whereas,the level of NSE in the group with brain parenchymal metastasis was lower than that in the control group.Conclusions:The basal levels of ProGRP and NSE in normal cerebrospinal fluid were significantly higher than those in the serum;whereas,the expression levels of other TM in the cerebrospinal fluid were significantly lower than those in the serum.Whether the levels of TM in the serum were elevated and whether brain parenchymal metastasis was present,did not have a clinically significant impact on the TM levels in the cerebrospinal fluid.