食管和贲门癌及癌前病变患者血清中多个自身抗体的检测及其临床意义

Detection of multiple serum autoantibody in patients with esophageal and gastric cardia precancerous and cancerous lesion using tumor-associated antigens mini-array

目的:探讨食管和贲门癌及癌前病变患者血清中多个肿瘤相关自身抗体的变化特征及其在食管和贲门癌高危人群筛查和早期诊断中的意义。方法:应用间接酶联免疫反应法和肿瘤相关抗原微阵列(包含8个重组的癌抗原蛋白:C-myc、p53、cyclinB1、p16、p62、Koc、IMP1和Survivin)检测376例食管和贲门各级病变患者(正常、癌前病变和癌)血清中的自身抗体。结果:在所检测的八种抗原中,p53、C-myc、cyclinB1、IMP1和p62从正常食管到癌前病变及癌患者血清中和p53、C-myc、p16、p62在正常贲门到癌前病变及癌患者血清中阳性百分率均具有线性升高趋势。单一抗体对食管和贲门癌检出率较低,p53在癌血清中的表达阳性率在所有抗原中最高,在食管癌和贲门癌患者中分别为23%(13/57)和21%(9/43)。但是,当应用8个抗原分析时,至少有1个反应为阳性时,其检出阳性率明显增高,食管和贲门癌的阳性检出率分别提高到63%(36/57)和61%(26/43),上述检测指标在正常食管和贲门与相应各级癌前病变和癌患者阳性表达率差异有统计学意义,P<0·05。结论:联合应用多个肿瘤相关抗原比应用单个肿瘤相关抗原分析食管和贲门癌及癌前病变患者血清中的自身抗体变化能够提高癌和癌前病变患者的检出率。食管和贲门癌多个相关抗原微阵列的进一步优化有可能成为临床上食管和贲门癌和高危人群检测和早期诊断的非侵袭性方法。

OBJECTIVE：To characterize the alterations of multiple autoantibodies of tumor-associated antigens in serum from the subjects with esophageal and gastric cardia precancerous and cancerous lesions and to determine the significance of these changes in high-risk subject screening and early diagnosis of esophageal and gastric cardia cancers. METHODS： Enzyme-linked immunoassay and tumorassociated antigen mini-array （consisting of eight full length recombinant proteins, including C-myc, p53, cyclinB1, p62, p16, Koc, IMP1, Survivin） were applied to determine the serum level of the autoantibodies of these antigens on 376 subjects with esophageal and gastric cardia precancerous and cancerous lesions. RESULTS：In all of the 8 antigens de termined,the linear correlation was observed between the detection frequency of p53.C-myc and p62 and the multi-slage progression from normal to precancerous and cancerous lesions both in esophageal and in gastric cardia carcinogenesis （P〈0.05）. The other markers related lesion progression were cyclinB1 and IMPI in esophageal carcinogenesis and p16 in gastric cardia carcinogenesis. The detection rate with single positive autoantibody immunoreactivity for both esophageal and gastric cardia cancers was low. The p53 positive immunoreactivity was 23% （13/57） in esophageal cancer and 21% （9/43） in gastric cardia cancer. How ever,the positive detection rate for both esophageal and gastric cardia cancer increased apparently when the multiple positive markers were combined together for analysis,which increased to 63% （36/57） and 61% （26/43）, respectively. Furthermore,the difference in autoantibody immunoreactive rate was significant with the lesion progressed from mild to severe and to cancer both in esophageal and gastric cardia cancers, P〈0. 05. CONCLUSIONS： The screening rate through serum tumor associated antigen mini-array for the subjects with esophageal and gastric cardia precancerous and cancerous lesions has been increased apparently with combined analysis of multiple autoantibodies compared with the single one. The further dedicated design with multiple tumor-associated antigens mini-array unique for esophageal and gastric cardiac cancers may contribute a clinically potential noninvasive approach to the high-risk subiect screening and early cancer diagnosis.