期刊
CANCER MEDICINE
卷 7, 期 5, 页码 1802-1813出版社
WILEY
DOI: 10.1002/cam4.1449
关键词
AlphaLISA; biomarker; esophageal squamous cell carcinoma; exosomes; stathmin-1
类别
资金
- National Natural Science Foundation [81572840, 91629105, 81572365, 81728015]
- National Key R D Program [2017YFC0906600, 2017ZX10203205-003, 2016YGC0901403]
- State Key Project for Basic Research of China [2014CBA02001, 2014CBA02002]
- CAMS Innovation Fund for Medical Sciences [2016-I2M-1-001, 2017-I2M-3-005]
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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