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Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker

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Author(s)
Chang Min Kim Shin Hwang Bhumsuk Keam Yun Suk Yu Ji Hoon Kim Dong-Sik Kim Si Hyun Bae Gun-Do Kim Jong Kyu Lee Yong Bae Seo Soon Woo Nam Koo Jeong Kang Luigi Buonaguro Jin Young Park Yun Soo Kim Hee Jung Wang
Keimyung Author(s)
Kang, Koo Jeong
Department
Dept. of Surgery (외과학)
Journal Title
Liver cancer
Issued Date
2020
Volume
9
Issue
2
Keyword
SorafenibBiomarkerGene signatureHepatocellular carcinoma
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.
Keimyung Author(s)(Kor)
강구정
Publisher
School of Medicine (의과대학)
Citation
Chang Min Kim et al. (2020). Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker. Liver cancer, 9(2), 182–192. doi: 10.1159/000504548
Type
Article
ISSN
1664-5553
Source
https://www.karger.com/Article/FullText/504548
DOI
10.1159/000504548
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43235
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Surgery (외과학)
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