Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma

Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma
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DOI:
10.1002/ijc.20517
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发表时间:
2004-12-20
影响因子:
6.4
通讯作者:
Hiwasa, T
Hiwasa, T
中科院分区:
医学1区
文献类型:
--
作者:
Nakashima, K;Shimada, H;Hiwasa, T

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我们应用血清学分析的重组cDNA表达文库(SEREX)的情况下,食管鳞状细胞癌(SCC),以确定肿瘤抗原。其中一个克隆是TROP 2,它被称为钙信号转导子。为了评价食管鳞癌患者血清中抗TROP 2抗体(s-TROP 2-Abs)的临床意义,使用细菌表达的TROP 2蛋白通过Western印迹分析s-TROP 2-Abs的存在。我们发现75例患者中有23例(31%)为s-TROP 2-Ab阳性。s-TROP 2-Ab阳性与肿瘤大小显著相关,但与其他临床病理特征无关。TROP 2在食管鳞癌细胞系中的蛋白表达水平明显高于正常食管粘膜及其永生化细胞,但在恶性肿瘤细胞系和组织中的mRNA表达水平不一定升高。免疫组化结果显示,食管鳞状细胞癌组织中TROP 2蛋白的表达明显高于食管粘膜轻度增生组织。因此,s-TROP 2-Abs在SCC的诊断中可能是有用的,并且可能是血清肿瘤标志物的候选者。(C)2004 Wiley-Liss,Inc.
We applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti-TROP2 antibodies (s-TROP2-Abs) in patients with esophageal SCC, the presence of s-TROP2-Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s-TROP2-Abs. Positivity in terms of s-TROP2-Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s-TROP2-Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers. (C) 2004 Wiley-Liss, Inc.