scholarly journals Comparison of circulating tumor cell (CTC) detection rates with epithelial cell adhesion molecule (EpCAM) and cell surface vimentin (CSV) antibodies in different solid tumors: a retrospective study

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10777
Author(s):  
Yang Gao ◽  
Wan-Hung Fan ◽  
Zhengbo Song ◽  
Haizhou Lou ◽  
Xixong Kang

Purpose Status of epithelial-mesenchymal transition (EMT) varies from tumors to tumors. Epithelial cell adhesion molecule (EpCAM) and cell surface vimentin (CSV) are the most common used targets for isolating epithelial and mesenchymal CTCs, respectively. This study aimed to identify a suitable CTC capturing antibody for CTC enrichment in each solid tumor by comparing CTC detection rates with EpCAM and CSV antibodies in different solid tumors. Methods Treatment-naive patients with confirmed cancer diagnosis and healthy people who have performed CTC detection between April 2017 and May 2018 were included in this study. CTC detection was performed with CytoSorter® CTC system using either EpCAM or CSV antibody. In total, 853 CTC results from 690 cancer patients and 72 healthy people were collected for analysis. The performance of CTC capturing antibody was determined by the CTC detection rate. Results EpCAM has the highest CTC detection rate of 84.09% in CRC, followed by BCa (78.32%). CTC detection rates with EpCAM antibody are less than 40% in HCC (25%), PDAC (32.5%) and OC (33.33%). CSV has the highest CTC detection rate of 90% in sarcoma, followed by BC (85.71%), UC (84.62%), OC (83.33%) and BCa (81.82%). CTC detection rates with CSV antibody are over 60% in all 14 solid tumors. Except for CRC, CSV has better performances than EpCAM in most solid tumors regarding the CTC detection rates. Conclusion EpCAM can be used as a target to isolate CTCs in CRC, LC, GC, BCa, EC, HNSCC, CC and PCa, especially in CRC, while CSV can be used in most solid tumors for isolating CTCs.

2015 ◽  
Vol 61 (1) ◽  
pp. 259-266 ◽  
Author(s):  
Arun Satelli ◽  
Zachary Brownlee ◽  
Abhisek Mitra ◽  
Qing H Meng ◽  
Shulin Li

Abstract BACKGROUND Detection, isolation, and enumeration of circulating tumor cells (CTCs) from cancer patients has become an important modality in clinical management of patients with breast cancer. Although CellSearch, an epithelial cell adhesion molecule (EpCAM)-based method that is used to isolate epithelial CTCs, has gained prominence, its inability to detect mesenchymal CTCs from breast cancer patients raises concerns regarding its utility in clinical management. METHODS To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma tumors. In the present study, we tested the sensitivity and specificity of detecting CTCs from blood collected at a random time during therapy from each of 58 patients with metastatic breast cancer by use of 84-1 (a monoclonal antibody against CSV to detect epithelial/mesenchymal-transition CTCs) and CellSearch methods. Additionally, we tested the possibility of improving the sensitivity and specificity of detection by use of additional parameters including nuclear EpCAM localization and epithelial mesenchymal ratios. RESULTS CTC counts with CSV were significant (P = 0.0053) in differentiating populations responsive and nonresponsive to treatment compared with CTC counts with CellSearch (P = 0.0564). The specificity of CTC detection was found to be highest when the sum of CTC counts from the 2 methods was above a threshold of 8 CTCs/7.5 mL. CONCLUSIONS The sum of CTC counts from the CellSearch and CSV methods appears to provide new insights for assessment of therapeutic response and thus provides a new approach to personalized medicine in breast cancer patients.


Author(s):  
Fatemeh Sadat Javadian ◽  
Majid Basafa ◽  
Aidin Behravan ◽  
Atieh Hashemi

Abstract Background Overexpression of the EpCAM (epithelial cell adhesion molecule) in malignancies makes it an attractive target for passive immunotherapy in a wide range of carcinomas. In comparison with full-length antibodies, due to the small size, the scFvs (single-chain variable fragments) are more suitable for recombinant expression in E. coli (Escherichia coli). However, the proteins expressed in large amounts in E. coli tend to form inclusion bodies that need to be refolded which may result in poor recovery of bioactive proteins. Various engineered strains were shown to be able to alleviate the insolubility problem. Here, we studied the impact of four E. coli strains on the soluble level of anti-EpEX-scFv (anti-EpCAM extracellular domain-scFv) protein. Results Although results showed that the amount of soluble anti-EpEX-scFv obtained in BL21TM (DE3) (114.22 ± 3.47 mg/L) was significantly higher to those produced in the same condition in E. coli RosettaTM (DE3) (71.39 ± 0.31 mg/L), and OrigamiTM T7 (58.99 ± 0.44 mg/L) strains, it was not significantly different from that produced by E. coli SHuffleTM T7 (108.87 ± 2.71 mg/L). Furthermore, the highest volumetric productivity of protein reached 318.29 ± 26.38 mg/L in BL21TM (DE3). Conclusions Although BL21TM (DE3) can be a suitable strain for high-level production of anti-EpEX-scFv protein, due to higher solubility yield (about 55%), E. coli SHuffleTM T7 seems to be better candidate for soluble production of scfv compared to BL21TM (DE3) (solubility yield of about 30%).


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