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目的 :应用蛋白质芯片检测食管癌及癌前病变患者血清中的自身抗体,寻找有利于筛查食管癌和癌前病变患者的血清抗体标志物。方法 :应用55种肿瘤相关抗原(tumor-associated antigens,TAAs)蛋白质芯片检测26例食管癌患者、26例食管癌前病变患者和26例正常对照人群血清中的自身抗体。正常组血清抗体表达水平以均数±2倍标准差作为cut-of值(截断值),读数在此数值范围以外的为阳性,否则为阴性。结果 :在55种TAAs对应的血清自身抗体检测中,随病程变化表达呈线性上调的有CA72-4、NY-ESO-1、CYFRA21-1、GAGE-7和SCCA,共5个抗体;其他抗体表达水平均随病变演进呈线性下降趋势。多因素方差分析3组间表达水平有统计学差异的抗体共25种,其中以截断值作为诊断标准时,能够检测到血清抗体阳性的抗原有CA72-4、CCNB1、CDKN2A、NY-ESO-1、CYFRA21-1、E2F1、ERBB2、GAGE-7和SCCA共9种。CYFRA21-1血清抗体阳性检出率在食管癌和癌前病变中分别是61.54%和60.00%,其他阳性率较高的抗体依次为NY-ESO-1(50.00%vs52.00%)、SCCA(46.15%vs 48.00%)、GAGE-7(46.15%vs 24.00%)和CA72-4(34.62%vs 16.00%)。9个抗原联合分析时,食管癌和癌前病变患者的检出率高达88.46%和84.00%。结论 :CYFRA21-1抗体可能作为食管癌及癌前病变早期筛查的单个肿瘤标志物。多个TAAs联合检测食管癌及癌前病变患者血清中的自身抗体可提高检测的敏感度。
OBJECTIVE: To detect autoantibodies in serum of patients with esophageal cancer and precancerous lesions by using protein microarray, and to find serum antibody markers for screening esophageal and precancerous lesions. METHODS: Fifty-five tumor-associated antigens (TAAs) protein chips were used to detect autoantibodies in serum of 26 esophageal cancer patients, 26 esophageal precancerous lesions and 26 normal controls. Normal group serum antibody expression level with mean ± 2 times the standard deviation as the cut-of value (cut-off value), readings outside this range of values is positive, otherwise negative. Results: Among the 55 kinds of TAAs, the serum autoantibodies detected showed a linear up-regulation of CA72-4, NY-ESO-1, CYFRA21-1, GAGE-7 and SCCA, The expression levels showed a linear decrease with the progression of the lesion. Multivariate analysis of variance showed that there were 25 kinds of antibodies with statistically significant differences among the three groups. Among them, the cutoff value was used as the diagnostic criteria to detect the antibody positive for CA72-4, CCNB1, CDKN2A, NY-ESO-1, 9 CYFRA21-1, E2F1, ERBB2, GAGE-7 and SCCA. The positive rates of CYFRA21-1 seropositivity in esophageal cancer and precancerous lesions were 61.54% and 60.00%, respectively. The other antibodies with higher positive rates were NY-ESO-1 (50.00% vs52.00%), SCCA ( 46.15% vs 48.00%), GAGE-7 (46.15% vs 24.00%) and CA72-4 (34.62% vs 16.00%). When combined with 9 antigens, the detection rates of esophageal cancer and precancerous lesions were 88.46% and 84.00% respectively. Conclusion: CYFRA21-1 antibody may be used as a single tumor marker for early screening of esophageal and precancerous lesions. Multiple TAAs in combination with autoantibodies in the serum of patients with esophageal and precancerous lesions increase the sensitivity of the assay.