Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
- Authors
- Kim C.M.; Hwang S.; Keam B.; Yu Y.S.; Kim J.H.; Kim D.-S.; Bae S.H.; Kim G.-D.; Lee J.K.; Seo Y.B.; Nam S.W.; Kang K.J.; Buonaguro L.; Park J.Y.; Kim Y.S.; Wang H.J.
- Issue Date
- Apr-2020
- Publisher
- S. Karger AG
- Keywords
- Biomarker; Gene signature; Hepatocellular carcinoma; Sorafenib
- Citation
- Liver Cancer
- Journal Title
- Liver Cancer
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/26324
- DOI
- 10.1159/000504548
- ISSN
- 2235-1795
- Abstract
- Background/Aim: Uniform treatment of hepatocellular carcinoma (HCC) with molecular targeted drugs (e.g., sorafenib) results in a poor overall tumor response when tumor subtyping is absent. Patient stratification based on actionable gene expression is a method that can potentially improve the effectiveness of these drugs. Here we aimed to identify the clinical application of actionable genes in predicting response to sorafenib. Methods: Through quantitative real-time reverse transcription PCR, we analyzed the expression levels of seven actionable genes (VEGFR2, PDGFRB, c-KIT, c-RAF, EGFR, mTOR, and FGFR1) in tumors versus noncancerous tissues from 220 HCC patients treated with sorafenib. Our analysis found that 9 responders did not have unique clinical features compared to nonresponders. A receiver operating characteristic curve evaluated the predictive performance of the treatment benefit score (TBS) calculated from the actionable genes. Results: The responders had significantly higher TBS values than the nonresponders. With an area under the curve of 0.779, a TBS combining mTOR with VEGFR2, c-KIT, and c-RAF was the most significant predictor of response to sorafenib. When used alone, sorafenib had a 0.7-3% response rate among HCC patients, but when stratifying the patients with actionable genes, the tumor response rate rose to 15.6%. Furthermore, actionable gene expression is significantly correlated with tumor response. Conclusions: Our findings on patient stratification based on actionable molecular subtyping potentially provide a therapeutic strategy for improving sorafenib's effectiveness in treating HCC. © 2020 The Author(s).
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 의과대학 > 의학과 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/26324)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.