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检测针对P53、IMP1、P16、细胞周期蛋白B1、P62、C-myc、生存素和Koc等肿瘤相关抗原的自身抗体,用于高危人群筛查和食管鳞状细胞癌的早期检测。

Autoantibody detection to tumor-associated antigens of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn, and Koc for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma.

作者信息

Zhou S L, Yue W B, Fan Z M, Du F, Liu B C, Li B, Han X N, Ku J W, Zhao X K, Zhang P, Cui J, Zhou F Y, Zhang L Q, Fan X P, Zhou Y F, Zhu L L, Liu H Y, Wang L D

机构信息

Henan Key Laboratory for Esophageal Cancer Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Dis Esophagus. 2014 Nov-Dec;27(8):790-7. doi: 10.1111/dote.12145. Epub 2013 Oct 21.

Abstract

The aim of this study was to evaluate the diagnostic values by detecting sera autoantibodies to eight tumor-associated antigens (TAAs) of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn and Koc full-length recombinant proteins for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma (ESCC). Enzyme-linked immunosorbent assay was used to detect autoantibodies against the eight selected TAAs in 567 sera samples from four groups, including 200 individuals with normal esophageal epithelia (NOR), 214 patients with esophageal basal cell hyperplasia (BCH), 65 patients with esophageal dysplasia (DYS), and 88 patients with ESCC. In addition, the expression of the eight antigens in esophageal tissues was analyzed by immunohistochemistry. Statistically significant distribution differences were identified among the four groups for each of the individual autoantibodies to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C-myc); the detection rates of antoantibodies were positively correlated with the progression of ESCC. When autoantibody assay successively accumulated to six TAAs (P53, IMP1, P16, cyclin B1, P62, and C-myc), a stepwise increased detection frequency of autoantibodies was found in the four sera groups (6% in NOR, 18% in BCH, 38% in DYS, and 64% in ESCC, respectively), the risks to BHC, DYS, and ESCC steadily increased about 3-, 9-, and 27-folds. The sensitivity and the specificity for autoantibodies against the six TAAs in diagnosing ESCC reached up to 64% and 94%, respectively. The area under the receiver operating characteristic curve for the six anti-TAA autoantibodies was 0.78 (95% confidence interval 0.74-0.83). No more increasing in sensitivity was found with the addition of new anti-TAA autoantibodies. A combination detection of autoantibodies to TAAs might distinguish ESCC patients from normal individuals and the patients with esophageal precancerous lesions.

摘要

本研究旨在通过检测血清中针对P53、IMP1、P16、细胞周期蛋白B1、P62、C-myc、Survivn和Koc全长重组蛋白这八种肿瘤相关抗原(TAA)的自身抗体,评估其对高危人群的筛查及食管鳞状细胞癌(ESCC)早期检测的诊断价值。采用酶联免疫吸附测定法检测四组567份血清样本中针对上述八种选定TAA的自身抗体,这四组包括200例食管上皮正常个体(NOR)、214例食管基底细胞增生患者(BCH)、65例食管发育异常患者(DYS)和88例ESCC患者。此外,通过免疫组织化学分析这八种抗原在食管组织中的表达。对于六种TAA(P53、IMP1、P16、细胞周期蛋白B1、P62和C-myc)各自的单个自身抗体,四组之间存在统计学上显著的分布差异;自身抗体的检测率与ESCC的进展呈正相关。当自身抗体检测依次累积至六种TAA(P53、IMP1、P16、细胞周期蛋白B1、P62和C-myc)时,在四组血清中发现自身抗体的检测频率逐步增加(NOR组为6%,BCH组为18%,DYS组为38%,ESCC组为64%),BHC、DYS和ESCC的风险分别稳步增加约3倍、9倍和27倍。针对六种TAA的自身抗体诊断ESCC的敏感性和特异性分别高达64%和94%。六种抗TAA自身抗体的受试者工作特征曲线下面积为0.78(95%置信区间0.74 - 0.83)。添加新的抗TAA自身抗体后未发现敏感性进一步增加。TAA自身抗体的联合检测可能区分ESCC患者与正常个体以及食管癌前病变患者。

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