非小细胞肺癌患者血清中纤维母细胞生长因子受体表达意义及其与血清肿瘤标志物的相关性研究

目的 研究非小细胞肺癌患者血清中纤维母细胞生长因子受体(fibroblast growth factor receptor-1,FGFR1)表达意义及其与血清肿瘤标志物的相关性。方法 研究对象选取我院收治的非小细胞肺癌患者65例,并选取同期14例肺良性病变患者、25例原发性肝癌患者及35名健康体检者作为对照组,应用实时荧光定量聚合酶链反应法检测各组受试者血清FGFR1 DNA表达水平,采用电化学发光法检测肺癌患者血清癌胚抗原(carcinoembryonic antigen,CEA)、细胞角蛋白(cytokeratin-19-fragment,Cyfra21-1)以及神经特异性烯醇化酶(neuron specific enolase,NSE)水平。比较各组血清FGFR1 DNA表达水平的差异并进行ROC曲线分析血清FGFR1水平诊断肺癌的准确性。采用Pearson相关性分析法分析肺癌患者血清FGFR1表达水平与CEA、Cyfra21-1及NSE的相关性。结果 单因素方差分析显示:各组血清FGFR1 DNA表达水平差异具有统计学意义(F=249.38,P<0.001);且肺癌患者血清FGFR1 DNA表达水平明显高于良性病变组(t=11.41,P<0.01)、肝癌组(t=9.09,P<0.01)及健康组(t=36.96,P<0.01);不同临床特征肺癌患者血清FGFR1 DNA表达水平具有明显差异,其中鳞癌患者血清FGFR1表达水平明显高于腺癌和其他肺癌(F=45.22,P<0.001),晚期(Ⅲ~Ⅳ)肺癌患者明显高于早期(Ⅰ~Ⅱ)肺癌患者(F=171.11,P<0.001),淋巴结转移阳性患者明显高于阴性患者(F=125.34,P<0.001)。ROC曲线分析显示:AUC=0.904>0.5具有诊断价值,最佳诊断临界值为1.79×10^5copies/μL,灵敏度为94.65%,特异性为82.76%。Pearson相关性分析显示:鳞癌患者血清FGFR1表达与CEA、Cyfra21-1及NSE均呈明显正相关(P<0.05),其中与Cyfra21-1的相关性最大(r=0.528);腺癌患者血清FGFR1表达与CEA呈弱相关关系(r=0.145,P=0.03),与Cyfra21-1、NSE均无明显相关性;其他类型肺癌患者血清FGFR1表达与CEA、Cyfra21-1及NSE均无明显相关性(P>0.05)。结论 肺癌患者血清FGFR1表达具有显著的临床意义,在肺癌的诊断中具有较高的诊断效能,另外FGFR1的表达与血清肿瘤标志物具有明显相关性,进一步表明其在肺癌的诊断、病理分型及预后的评估等方面具有重要临床意义。

The Expression of Fibroblast Growth Factor Receptor in Serum of Patients with Lung Cancer and Its Correlation with Serum Tumor Markers

Objective To investigate the expression of Fibroblast Growth Factor Receptor(FGFR)in serum of patients with non-small cell lung cancer and its correlation with serum tumor markers.Methods 65 patients with non-small cell lung cancer admitted to our hospital were enrolled in the study.14 patients with benign lung disease,25 patients with primary liver cancer and 35 healthy subjects were selected as the control group.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to detect serum FGFR1 DNA expression in each group.The levels of serum carcinoembryonic antigen(CEA),cytokeratin(Cyfra 21-1)and neuron specific enolase(NSE)levels in lung cancer patients were detected by electrochemiluminescence.The differences of serum FGFR1 DNA expression levels among the groups were compared and the accuracy of serum FGFR1 levels in the diagnosis of lung cancer was evaluated by ROC curve.Pearson correlation analysis was used to analyze the correlation between serum FGFR1 expression and CEA,Cyfra21-1 and NSE in lung cancer patients.Results One-way analysis of variance showed that the serum FGFR1 DNA expression levels crossing groups were significantly different,(F=249.38,P<0.001).The serum FGFR1 DNA expression levels in lung cancer patients was significantly higher than that in benign lesions(t =11.41,P<0.01),liver cancer group(t=9.09,P<0.01)and healthy group(t=36.96,P<0.01).The serum FGFR1 DNA of patients with different clinical characteristics of lung cancer showed different expression levels.The serum FGFR1 expression level of squamous cell carcinoma patients was significantly higher than that of adenocarcinoma and other lung cancers(F=45.22,P<0.001).The advanced(III^IV)lung cancer patients were significantly higher than the early(I-II)lung cancer patients(F=171.11,P<0.001).The lymph node metastasis positive patients were significantly higher than negative patients(F=125.34,P<0.001).ROC curve analysis showed that AUC=0.904 greater than 0.5 with the diagnostic value,and the optimal diagnostic threshold was 1.79×10^5copies/μL,also the sensitivity was 97.02%,and the specificity was 80.95%.Pearson correlation analysis showed that serum FGFR1 expression was positively correlated with CEA,Cyfra21-1 and NSE(P<0.05),and the most correlated with Cyfra21-1(r=0.528);There was a weak correlation between FGFR1 expression and CEA(r=0.145,P=0.03),and no correlation with Cyfra21-1 and NSE.There was no significant correlation between serum FGFR1 expression and CEA,Cyfra21-1 and NSE in other types of lung cancer patients(P>0.05).Conclusion The expression of serum FGFR1 in lung cancer patients has a significant clinical significance and a high diagnostic efficiency in the diagnosis of lung cancer.In addition,the expression of FGFR1 is significantly correlated with serum tumor markers,further indicating its diagnostic and pathological classification in lung cancer.And the evaluation of prognosis has important clinical significance.