Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
- Authors
- Kim, Chang Min; Hwang, Shin; Keam, Bhumsuk; Yu, Yun Suk; Kim, Ji Hoon; Kim, Dong-Sik; Bae, Si Hyun; Kim, Gun-Do; Lee, Jong Kyu; Seo, Yong Bae; Nam, Soon Woo; Kang, Koo Jeong; Buonaguro, Luigi; Park, Jin Young; Kim, Yun Soo; Wang, Hee Jung
- Issue Date
- 4월-2020
- Publisher
- KARGER
- Keywords
- Sorafenib; Biomarker; Gene signature; Hepatocellular carcinoma
- Citation
- LIVER CANCER, v.9, no.2, pp.182 - 192
- Indexed
- SCIE
SCOPUS
- Journal Title
- LIVER CANCER
- Volume
- 9
- Number
- 2
- Start Page
- 182
- End Page
- 192
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/56698
- 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.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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