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

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

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)


    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 languageEnglish
    Pages (from-to)182-192
    Number of pages11
    JournalLiver Cancer
    Issue number2
    Publication statusPublished - 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.


    • Biomarker
    • Gene signature
    • Hepatocellular carcinoma
    • Sorafenib

    ASJC Scopus subject areas

    • Hepatology
    • Oncology


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