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Cited 8 time in webofscience Cited 7 time in scopus
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Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarkeropen access

Authors
Kim, Chang MinHwang, ShinKeam, BhumsukYu, Yun SukKim, Ji HoonKim, Dong-SikBae, Si HyunKim, Gun-DoLee, Jong KyuSeo, Yong BaeNam, Soon WooKang, Koo JeongBuonaguro, LuigiPark, Jin YoungKim, Yun SooWang, Hee Jung
Issue Date
Apr-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://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/903
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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2. Clinical Science > Department of Hepato-Biliary-Pancreatic Surgery > 1. Journal Articles
2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles

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Kim, Ji Hoon
구로병원 (Department of Gastroenterology and Hepatology, Guro Hospital)
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