Open AccessExtra-domain B of fibronectin as an alternative target for drug delivery and a cancer diagnostic and prognostic biomarker for malignant glioma
Author(s) -
Phei Er Saw,
Xiaoding Xu,
Bo Kang,
Jungsul Lee,
Yeo Song Lee,
Chungyeul Kim,
Hyungsin Kim,
ShinHyuk Kang,
Yoo Jin Na,
Hong Joo Moon,
Joo Han Kim,
Youn-Kwan Park,
Won Ki Yoon,
Jong Hyun Kim,
Taek-Hyun Kwon,
Chulhee Choi,
Sangyong Jon,
Kyuha Chong
Publication year - 2021
Publication title -
theranostics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.689
H-Index - 97
ISSN - 1838-7640
DOI - 10.7150/thno.44948
Subject(s) - fibronectin , in vivo , glioma , cancer research , cancer , microarray , biomarker , tissue microarray , docetaxel , chemistry , extracellular matrix , medicine , microbiology and biotechnology , biology , gene expression , gene , biochemistry
Extra-domain B of fibronectin (EDB-FN) is an alternatively spliced form of fibronectin with high expression in the extracellular matrix of neovascularized tissues and malignant cancer cells. In this study, we evaluated the practicality of using EDB-FN as a biomarker and therapeutic target for malignant gliomas (MGs), representative intractable diseases involving brain tumors. Methods: The microarray- and sequence-based patient transcriptomic database 'Oncopression' and tissue microarray of MG patient tissue samples were analyzed. EDB-FN data were extracted and evaluated from 23,344 patient samples of 17 types of cancer to assess its effectiveness and selectivity as a molecular target. To strengthen the results of the patient data analysis, the utility of EDB-FN as a molecular marker and target for MG was verified using active EDB-FN-targeting ultrasmall lipidic micellar nanoparticles (~12 nm), which had a high drug-loading capacity and were efficiently internalized by MG cells in vitro and in vivo . Results: Brain tumors had a 1.42-fold cancer-to-normal ratio ( p < 0.0001), the second highest among 17 cancers after head and neck cancer. Patient tissue microarray analysis showed that the EDB-FN high-expression group had a 5.5-fold higher risk of progression than the EDB-FN low-expression group ( p < 0.03). By labeling docetaxel-containing ultrasmall micelles with a bipodal aptide targeting EDB-FN (termed APT EDB -DSPE-DTX), we generated micelles that could specifically bind to MG cells, leading to superior antitumor efficacy of EDB-FN-targeting nanoparticles compared to nontargeting controls. Conclusions: Taken together, these results show that EDB-FN can be an effective drug delivery target and biomarker for MG.