Application value of ST2 combined with CEA and CYFRA211 in diagnosis of early non-small cell lung cancer
Received date: 2023-09-21
Online published: 2024-03-15
目的:探索3种生物标志物可溶性生长刺激表达基因2蛋白(soluble growth stimulation expressed gene 2 protein, ST2)、癌胚抗原(carcinoembryonic antigen,CEA)和CYFRA211(细胞角蛋白质19片段中的21和1表位)辅助诊断早期非小细胞肺癌(non-small cell lung cancer,NSCLC)价值。方法:收集2023年1月至8月期间上海交通大学医学院附属瑞金医院收治的91例早期NSCLC患者(TNM分期Ⅰ期)、21例中晚期NSCLC患者(TNM分期Ⅱ期16例、Ⅲ期5例),另选取同期的50例肺部良性病变患者及50例健康体检人群作为正常对照。用荧光免疫层析法检测所有研究对象的血浆ST2水平,用化学微粒子发光法检测其血清CEA、CYFRA211水平,比较组间差异,并分析单个或联合指标诊断NSCLC的价值。结果:检测ST2水平后发现,NSCLC早期组要高于肺部良性病变组和健康对照组(P<0.001),肺部良性病变组要高于健康对照组(P<0.001)。NSCLC早期组的CEA浓度水平要高于健康对照组(P<0.05)、肺部良性病变组要高于健康对照组(P<0.05)。NSCLC早期组的CYFRA211浓度水平要高于健康对照组(P<0.05)。受试者操作特征(receiver operator characteristic, ROC)曲线分析显示,ST2、CEA、CYFRA211的临界值分别为≥25.0 ng/L、≥1.8 ng/mL、≥2.0 ng/mL时,其单独检测诊断早期NSCLC的曲线下面积分别为0.957、0.660、0.570;其中ST2的灵敏度和特异度分别为89.0%和98.0%,CEA和CYFRA211的灵敏度和特异度分别46.2%和80.0%、17.6%和96.0%;而三者联合检测诊断早期NSCLC的曲线下面积为0.973,灵敏度为92.3%、特异度为98.0%,均优于各项指标单独检测的结果。在临床病理特征中,肿瘤直径越大,NSCLC患者血浆ST2水平相对较高,差异具有统计学意义(P<0.05);患者CEA水平在不同的肿瘤分化程度的组别间、是否存在区域淋巴结转移的组别间、有无气道播散的组别间、是否浸润胸膜的组别间及TMN分期Ⅰ期组与Ⅱ、Ⅲ、Ⅳ期组间差异均有统计学意义;而CYFRA211水平则在患者的不同性别、不同年龄组别和不同肺癌类型组别(腺癌与鳞癌)中有统计学差异(P<0.05)。结论:相对于CEA和CYFRA211,单独检测ST2水平在区分NSCLC早期患者与肺部良性病变患者、健康对照人群中更有优势;而将三者联合检测,具有较高的诊断价值,可用于辅助诊断早期NSCLC。
关键词: 可溶性生长刺激表达基因2蛋白; 非小细胞肺癌; 癌胚抗原; 细胞角蛋白19片段
范臻佳, 赵珺涛, 周嘉宽, 李占权, 万颖蕾 . ST2联合CEA、CYFRA211在早期非小细胞肺癌辅助诊断中的应用价值[J]. 诊断学理论与实践, 2023 , 22(05) : 441 -447 . DOI: 10.16150/j.1671-2870.2023.05.004
Objective: To explore soluble growth stimulation expressed gene 2 protein (ST2), carcinoembryonic antigen(CEA) and cytokeratin fragment 21-1 (CYFRA211) in diagnosing early non-small cell lung cancer (NSCLC). Methods: From January to August 2023, 91 patients with early NSCLC (TNM stage Ⅰ) and 21 patients with middle and advanced NSCLC [TNM stage Ⅱ (16 cases) and Ⅲ (5 cases)] admitted to Ruijin Hospital were collected, and 50 patients with benign lung lesions(BL) and 50 healthy people(HC) were served as controls. Plasma ST2 levels were detected by fluorescence immunochromatography, and serum CEA and CYFRA211 levels were detected by chemiluminescence. The differences between groups were compared, and the diagnostic value of index alone or in combination for NSCLC was analyzed. Results: ST2 level in the early NSCLC group was higher than that in the BL and HC group (P<0.001), and ST2 level in BL group was higher than HC group (P<0.001). The CEA level in the early NSCLC group were higher than that in the HC group (P<0.05), BL group was higher than HC group (P<0.05). The CYFRA211 level in the early NSCLC group was higher than that in the HC group (P<0.05). When the cutoff values of ST2, CEA and CYFRA211 were set as 25.0 ng/L, 1.8 ng/mL and 2.0 ng/mL, areas under receiver operator characteristic (ROC) curve for diagnosing early NSCLC were 0.957, 0.660 and 0.570, respectively. The sensitivity of ST2,CEA and CYFRA211 for diagnosing early NSCLC were 89.0%, 46.2% and, 17.6%,and specificity were 98.0%, 80.0%, 96.0%, respectively. The area under the curve of the combined detection were 0.973, with a sensitivity of 92.3% and the specificity of 98.0%,which were higher than that of any index. In terms of clinicopathological features, plasma ST2 level was higher in NSCLC patients with larger tumors than with smaller tumors(P<0.05). There were statistical differences in CEA levels among groups with different degrees of tumor differentiation, between groups with and without regional lymph node metastasis, groups with and without airway spread, groups with and without pleural invasion, and groups with TMN stage Ⅰ and TMN Ⅱ/Ⅲ/Ⅳ(P<0.05). CYFRA211 levels were significantly different between diffe-rent sex groups, age groups and lung cancer types (P<0.05). Conclusions: Compared with CEA and CYFRA211, ST2 alone is more advantageous in distinguishing early NSCLC patients from patients with benign lung lesions and healthy controls. However, combined detection of the three tests has higher diagnostic value and is recommended to assist the diagnosis of early NSCLC.
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