Ren Z, Ding H M, Qian X, Pan S Y
Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2021 Dec 6;55(12):1426-1434. doi: 10.3760/cma.j.cn112150-20210511-00461.
To investigate the auxiliary diagnostic value of seven tumor-associated autoantibodies (AABs) P53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE in early non-small cell lung cancer (NSCLC). The case-control study enrolled 195 patients with early NSCLC [71 males and 124 females, aged (55.70±11.78) years old], 114 patients with benign lung disease [44 males and 70 females, aged (52.85±12.31) years old] and 100 healthy subjects [39 males and 61 females, aged (53.62±9.97) years old] from the First Affiliate Hospital of Nanjing Medical University from June 2020 to December 2020. AABs were detected by enzyme-linked-immunosorbent serologic assay (ELISA), and carcinoembryonic antigen (CEA),cytokeratin 19-fragments (CYFRA21-1) and neuron specific enolase (NSE) were detected by electrochemiluminescence. The levels of AABs,CEA,CYFRA21-1 and NSE in the 3 groups were compared. Patients with benign lung diseases and healthy subjects were combined into the control group, and the positive rate of each indicator in the NSCLC group and the control group was compared. The diagnostic efficacy of single and combined tests for NSCLC were obtained using receiver operating characteristic (ROC) curves. Besides, the relationship between the levels of AABs, CEA, CYFRA21-1 and NSE and their clinicopathological features and preoperative imaging parameters in NSCLC patients was assessed. The levels of SOX2 [0.70 (0.10, 2.40) U/mL] and GBU4-5 [1.30 (0.30, 8.90) U/mL] in NSCLC group were higher than those in benign disease group [SOX2: 0.50 (0.10, 1.60) U/mL, GBU4-5: 0.80 (0.10, 2.30) U/mL, values were 27.258 and 45.797; values were all<0.05] and health control group [SOX2: 0.45 (0.10, 1.08) U/mL, GBU4-5: 0.75 (0.20, 1.78) U/mL, values were 32.551 and 40.456; values were all<0.05], and there was no significant difference between benign disease group and health control group ( values were 5.293 and 5.340, values were all>0.05). The levels of CEA [1.75 (1.08, 2.72) U/mL] and CYFRA21-1 [1.81 (1.41, 2.36) U/mL] in NSCLC group were higher than those in healthy control group [CEA: 1.22 (0.68, 1.81) U/mL, CYFRA21-1: 1.43 (1.14, 1.74) U/mL, values were 64.100 and 37.597; values were all<0.05], but there was no significant difference between NSCLC group and benign group [CEA: 1.74 (1.01, 2.51) U/mL, CYFRA21-1: 1.82 (1.45, 2.46) U/mL, values were 7.275 and 10.621; values were all>0.05]. The positive rates of P53, SOX2, GAGE7, GBU4-5 and CEA in NSCLC group were higher than those in the control group [P53: 10.3% 0.9%, SOX2: 11.3% 2.3%, GAGE7: 11.3% 0.5%, GBU4-5: 30.1% 5.6%, CEA: 9.7% 0.9%, values were 17.420, 13.242, 22.485, 43.211, 16.255, respectively; values were all<0.05]. The diagnostic efficiency of the combined detection of seven AABs was better than that of single detection. Seven AABs combined with CEA [area under curve (AUC): 0.732, sensitivity: 64.10%] and with CYFRA21-1 (AUC: 0.737, sensitivity: 58.97%) greatly improved the diagnostic efficiency and sensitivity of CEA (AUC: 0.583, sensitivity: 50.77%) and CYFRA21-1 (AUC: 0.552, sensitivity: 44.10%). The levels of SOX2 and CEA in NSCLC patients were correlated with the degree of tumor invasion ( values were 6.436 and 14.071; values were all<0.05); the levels of GAGE7 and CEA were correlated with the nodule density ( values were 7.643 and 12.268; values were all<0.05); and the levels of SOX2, GAGE7, CEA and CYFRA21-1 were all correlated with the nodule size ( values were 10.837, 11.528, 31.835, 20.338; values were all<0.05). The detection of AABs combined with CEA and CYFRA21-1 is helpful for the early auxiliary diagnosis of NSCLC, and plays an important role in prevention and screening for early lung cancer.
探讨七种肿瘤相关自身抗体(AABs)P53、PGP9.5、SOX2、GAGE7、GBU4 - 5、MAGEA1和CAGE在早期非小细胞肺癌(NSCLC)中的辅助诊断价值。病例对照研究纳入了2020年6月至2020年12月期间来自南京医科大学第一附属医院的195例早期NSCLC患者[男性71例,女性124例,年龄(55.70±11.78)岁]、114例良性肺疾病患者[男性44例,女性70例,年龄(52.85±12.31)岁]和100例健康受试者[男性39例,女性61例,年龄(53.62±9.97)岁]。采用酶联免疫吸附血清学检测(ELISA)法检测AABs,采用电化学发光法检测癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21 - 1)和神经元特异性烯醇化酶(NSE)。比较三组中AABs、CEA、CYFRA21 - 1和NSE的水平。将良性肺疾病患者和健康受试者合并为对照组,比较NSCLC组和对照组各指标的阳性率。采用受试者工作特征(ROC)曲线获得NSCLC单项及联合检测的诊断效能。此外,评估NSCLC患者中AABs、CEA、CYFRA21 - 1和NSE水平与其临床病理特征及术前影像学参数之间的关系。NSCLC组中SOX2[0.70(0.10,2.40)U/mL]和GBU4 - 5[1.30(0.30,8.90)U/mL]的水平高于良性疾病组[SOX2:0.50(0.10,1.60)U/mL,GBU4 - 5:0.80(0.10,2.30)U/mL, 值分别为27.258和45.797; 值均<0.05]和健康对照组[SOX2:0.45(0.10,1.08)U/mL,GBU4 - 5:0.75(0.20,1.78)U/mL, 值分别为32.551和40.456; 值均<0.05],良性疾病组和健康对照组之间无显著差异( 值分别为5.293和5.340, 值均>0.05)。NSCLC组中CEA[1.75(1.08,2.72)U/mL]和CYFRA21 - 1[1.81(1.41,2.36)U/mL]的水平高于健康对照组[CEA:1.22(0.68,1.81)U/mL,CYFRA21 - 1:1.43(1.14,1.74)U/mL, 值分别为64.100和37.597; 值均<0.05],但NSCLC组和良性组之间无显著差异[CEA:1.74(1.01,2.51)U/mL,CYFRA21 - 1:1.82(1.45,2.46)U/mL, 值分别为7.275和10.621; 值均>0.05]。NSCLC组中P53、SOX2、GAGE7、GBU4 - 5和CEA的阳性率高于对照组[P53:10.3% 0.9%,SOX2:11.3% 2.3%,GAGE7:11.3% 0.5%,GBU4 - 5:30.1% 5.6%,CEA:9.7% 0.9%, 值分别为17.420、13.242、22.485、43.211、16.255; 值均<0.05]。七种AABs联合检测的诊断效能优于单项检测。七种AABs与CEA联合检测[曲线下面积(AUC):0.732,灵敏度:64.10%]和与CYFRA21 - 1联合检测(AUC:0.737,灵敏度:58.97%)大大提高了CEA(AUC:0.583,灵敏度:50.77%)和CYFRA21 - 1(AUC:0.552,灵敏度:44.10%)的诊断效能和灵敏度。NSCLC患者中SOX2和CEA的水平与肿瘤浸润程度相关( 值分别为6.436和14.071; 值均<0.05);GAGE7和CEA的水平与结节密度相关( 值分别为7.643和12.268; 值均<0.05);SOX2、GAGE7、CEA和CYFRA21 - 1的水平均与结节大小相关( 值分别为10.837、11.528、31.835、20.338; 值均<0.05)。AABs与CEA和CYFRA21 - 1联合检测有助于NSCLC的早期辅助诊断,在早期肺癌的预防和筛查中发挥重要作用。