A novel rapid quantitative method reveals stathmin-1 as a promising marker for esophageal squamous cell carcinoma.

A novel rapid quantitative method reveals stathmin-1 as a promising marker for esophageal squamous cell carcinoma.
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DOI:
10.1002/cam4.1449
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发表时间:
2018-05
期刊:
影响因子:
4
通讯作者:
Zhao X
Zhao X
中科院分区:
医学3区
文献类型:
--
作者:
Yan L;Dong X;Gao J;Liu F;Zhou L;Sun Y;Zhao X

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Stathmin-1是一种微管解聚蛋白,调节细胞的分裂、生长、迁移和侵袭。在多种人类肿瘤中,stathmin-1的过度表达与转移、预后不良和化疗耐药有关。我们先前的研究发现,通过ELISA检测,食管鳞癌(ESCC)患者血清stathmin-1显著升高。在这里,我们构建了高亲和力的单抗,然后建立了竞争性AlphaLISA,用于快速、准确地测定血清中stathmin-1的含量。与酶联免疫吸附试验相比,我们的均相AlphaLISA具有更高的灵敏度和准确度,更低的检测限和更宽的线性范围。对近1000例临床标本的检测表明,在鳞状细胞癌(SCC)尤其是ESCC患者中,血清stathmin-1水平显著升高,其敏感性和特异性分别为81%和94%。即使对于早期ESCC,stathmin-1在接收器工作特征曲线(AUC)下的面积也达到了0.88。同时,Stathmin-1浓度升高与淋巴结转移和肿瘤分期有关。值得注意的是,与腺癌相比,不同类型的鳞癌在血清stathmin-1检测中显示出显著更高的AUC。此外,我们证实stathmin-1在致癌外体中丰富,这可以解释它进入血液作为肿瘤替代物的原因。总之,我们新建立的AlphaLISA对血清stathmin-1进行的大规模和系统的研究表明,stathmin-1是一种非常有前途的临床鳞癌诊断和预测标记物,尤其是对ESCC。
Stathmin‐1 is a microtubule depolymerization protein that regulates cell division, growth, migration, and invasion. Overexpression of stathmin‐1 has been observed to be associated with metastasis, poor prognosis, and chemoresistance in various human cancers. Our previous studies found that serum stathmin‐1 was significantly elevated in patients with esophageal squamous cell carcinoma (ESCC) by ELISAs. Here, we constructed high‐affinity monoclonal antibodies and then developed a competitive AlphaLISA for rapid, accurate quantitation of stathmin‐1 in serum. Compared to ELISA, our homogeneous AlphaLISA showed better sensitivity and accuracy, a lower limit of detection, and a wider linear range. The measurements of nearly 1000 clinical samples showed that serum stathmin‐1 level increased dramatically in patients with squamous cell carcinoma (SCC), especially in ESCC, with a sensitivity and a specificity of 81% and 94%, respectively. Even for early stage ESCC, stathmin‐1 achieved an area under the receiver operating characteristic curve (AUC) of 0.88. Meanwhile, raised concentrations of stathmin‐1 were associated with lymph node metastasis and advanced cancer stage. Notably, various types of SCC showed significantly higher AUCs in serum stathmin‐1 detection compared to adenocarcinoma. Furthermore, we confirmed that stathmin‐1 was enriched in the oncogenic exosomes, which can explain the reason why it enters into the blood to serve as a tumor surrogate. In conclusion, this large‐scale and systematic study of serum stathmin‐1 measured by our newly established AlphaLISA showed that stathmin‐1 is a very promising diagnostic and predictive marker for SCC in the clinic, especially for ESCC.
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发表时间: 2015-03-10
期刊: BIOCHEMISTRY
影响因子: 2.9
作者:
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通讯作者: Bridges, Michael D.
DOI: 10.18632/oncotarget.18687
发表时间: 2017-09-22
期刊: Oncotarget
影响因子: --
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