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

Multiple autoantibody detection in esophageal cancerous or precancerous serum using tumor-associated antigens microarray

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 identify serum autoantibody biomarkers by an tumor-associated antigens （TAAs）-based microarray in the patients with esophageal precancerous lesions （EPLs） and patients with esophageal cancer （EC）. Methods： The antigens microarray with 55 TAAs was used to detect the serum autoantibodies of the residency-, age-, and sex-matched 26 pairs, which included 26 cases with EC, 26 cases with EPLs and 26 normal controls. The cut-off value was defined as mean _＋ 2 standard deviation of the expression levels of the antibodies in the normal control group. The value corresponding to the expression level of the antibody beyond the range of cut-off value was considered seropositive. Results： Five autoantibodies （CYFRA21-1, CA72-4, NY-ESO-1, GAGE-7 and SCCA）were significantly up-regulated, and others were down-regulated. Twenty-five autoantibodies had significant difference among EC, EPLs and normal controls which were found by multi-factor analysis of variance. Serum antibodies could be detected bv 9 antioens, includina CA72-4. CCNB1. CDKN2A. NY-ESO-1. CYFRA21-1. E2F1. ERBB2. GAGE-7and SCCA. The positive detection rates of CYFRA21-1 were the highest in EC and EPLs, which were 61.54% and 60.00%, respectively. Furthermore, other antigens with higher seropositive rates were NY-ESO-1 （50.00% for EC, 52.00% for EPLs）, SCCA （46.1 5% for EC, 48.00% for EPLs）, GAGE-7 （46.15% for EC, 24.00% for EPLs） and CA72-4 （34.62% for EC, 16.00% for EPLs） in turn. The seropositive rates of these 9 antigens in combined detection panel were 88.46% and 84.00% for EC and EPLs, respectively. Conclusion： CYFRA21 -1 is possibly used as an autoantibody indicator for early screening of EC and EPLs. The combined detection of the 9 antigens is likely to improve the sensitivity of autoantibody detection in EC and EPLs serum samples.