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.
Original language | English |
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Pages (from-to) | 182-192 |
Number of pages | 11 |
Journal | Liver Cancer |
Volume | 9 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2020 Apr 1 |
Bibliographical note
Funding Information:The research was supported in part by the Korea Cancer Biomarker Consortium.
Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (Grant No. NRF-2013R1A1A4A01009053) and the Gil Medical Center, Gachon University College of Medicine (Grant No. CBS2013-10), South Korea.
Publisher Copyright:
© 2020 The Author(s) Published by S. Karger AG, Basel.
Keywords
- Biomarker
- Gene signature
- Hepatocellular carcinoma
- Sorafenib
ASJC Scopus subject areas
- Hepatology
- Oncology