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

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.

Novel protein and immune response markers of human serous tubal intraepithelial carcinoma of the ovary

“…Until now, besides the established markers (TP53, p16, and Ki-67), several proteins were reported to be differentially expressed in STIC lesions including Stathmin 1 [19], signal transducer and activator of transcription 3 (phosphorylated STAT3 Tyr705) and suppression or loss of protein inhibitor of activated STAT3 (PIAS3) [20], Bcl-2 and γH2AX [21], Rsf-1 (HBXAP), cyclin E, and fatty acid synthase (FASN) [22], CD117 and ALDHA1 [23] and HMGA2 [24]. Of these proteins, differential circulating levels of Stathmin 1, FASN, ALDH1 were observed in esophageal, colorectal and lung cancers, and differential levels of Bcl-2 in OC, although none demonstrated high classification power [25][26][27][28][29]. With a better understanding in STIC development, new and better biomarkers for screening purposes can be envisioned.…”

Oncoprotein 18 is necessary for malignant cell proliferation in bladder cancer cells and serves as a G3-specific non-invasive diagnostic marker candidate in urinary RNA

“…Regarding OP18, also termed oncoprotein 18 and stathmin-1, immunohistochemical analyses of human donors and studies in the bladder cancer cell line T24 indicated that over-expression of OP18 is related to malignant cell characteristics. It is noteworthy that the role of increased expression of OP18 for tumor development and metastatic growth seems to be true also for other tumor types including esophageal squamous cell carcinoma [20,21] and lung adenocarcinoma [22]. In summary, these studies warrant a closer look at OP18 transcripts as an RNA-based tumor marker in BCa.…”

Exosomes in esophageal cancer: A review on tumorigenesis, diagnosis and therapeutic potential

“…Knockdown stathmin-1 expression enhanced the sensitivity of ESCC cell line to docetaxel and radiation[42]. Stathmin-1 can be delivered by exosomes and then promote the division, growth, migration, and invasion of esophageal squamous cells[43].…”

“…Studies have confirmed that the number or contents (including RNA and proteins) of exosomes in the circulating blood are of use as a biomarker for cancers, such as lung cancer[46], prostate cancer[47], colorectal cancer[48], as well as EC[18,28,43,49].…”

“…Stathmin-1 was abundant in exosomes and could enter peripheral blood loaded by exosomes[43]. Yan et al[43] found that the serum levels of stathmin-1 in ESCC patients with lymph node metastasis were significantly higher compared with the cases without lymph node metastasis. As the stage increased, its sensitivity improved accordingly.…”