Abstract
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.
Highlights
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in Asia and Africa
In our subsequent assays, the working concentrations of recombinant stathmin-1 protein (rSTMN) and 3P9 antibody were fixed to 25 and 156 ng/mL, respectively. In this system, biotinylated rSTMN1 protein competed with natural stathmin-1 in the samples to bind against the anti-stathmin-1 antibody, which forms the basis for the competing AlphaLISA (Fig. 1C)
We constructed high-affinity monoclonal antibodies of stathmin-1 and developed a competitive AlphaLISA for rapid, accurate quantitation of serum stathmin1 based on the homogeneous reaction
Summary
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer in Asia and Africa. Due to its asymptomatic nature in the early stage, most cases are diagnosed at advanced stages with poor prognosis. In China, it remains the fourth leading cause of cancer-related death [1]. Early detection of ESCC still depends on invasive endoscopic examinations [2]. There are no available serum markers for ESCC in AlphaLISA Detection of Stathmin-1 in ESCC the clinic. Squamous cell carcinoma antigen (SCC-Ag) and Cyfra21-1 showed low sensitivity in ESCC patients [3]. There is an urgent need to discover specific diagnostic markers for ESCC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
