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Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
by
Nam, Soon Woo
, Bae, Si Hyun
, Kim, Chang Min
, Kim, Dong-Sik
, Seo, Yong Bae
, Park, Jin Young
, Yu, Yun Suk
, Kim, Gun-Do
, Kim, Yun Soo
, Wang, Hee Jung
, Kang, Koo Jeong
, Kim, Ji Hoon
, Keam, Bhumsuk
, Buonaguro, Luigi
, Lee, Jong Kyu
, Hwang, Shin
in
Biomarkers
/ Biopsy
/ Cancer
/ Cancer therapies
/ Care and treatment
/ Chemotherapy
/ Dehydrogenases
/ Disease susceptibility
/ Gene expression
/ Genes
/ Genetic aspects
/ Genetic transcription
/ Hepatoma
/ Inhibitor drugs
/ Liver cancer
/ Magnetic resonance imaging
/ Medical research
/ Medicine, Experimental
/ Original Paper
/ Patients
/ Platelet-derived growth factor
/ Targeted cancer therapy
/ Tumors
2020
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Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
by
Nam, Soon Woo
, Bae, Si Hyun
, Kim, Chang Min
, Kim, Dong-Sik
, Seo, Yong Bae
, Park, Jin Young
, Yu, Yun Suk
, Kim, Gun-Do
, Kim, Yun Soo
, Wang, Hee Jung
, Kang, Koo Jeong
, Kim, Ji Hoon
, Keam, Bhumsuk
, Buonaguro, Luigi
, Lee, Jong Kyu
, Hwang, Shin
in
Biomarkers
/ Biopsy
/ Cancer
/ Cancer therapies
/ Care and treatment
/ Chemotherapy
/ Dehydrogenases
/ Disease susceptibility
/ Gene expression
/ Genes
/ Genetic aspects
/ Genetic transcription
/ Hepatoma
/ Inhibitor drugs
/ Liver cancer
/ Magnetic resonance imaging
/ Medical research
/ Medicine, Experimental
/ Original Paper
/ Patients
/ Platelet-derived growth factor
/ Targeted cancer therapy
/ Tumors
2020
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Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
by
Nam, Soon Woo
, Bae, Si Hyun
, Kim, Chang Min
, Kim, Dong-Sik
, Seo, Yong Bae
, Park, Jin Young
, Yu, Yun Suk
, Kim, Gun-Do
, Kim, Yun Soo
, Wang, Hee Jung
, Kang, Koo Jeong
, Kim, Ji Hoon
, Keam, Bhumsuk
, Buonaguro, Luigi
, Lee, Jong Kyu
, Hwang, Shin
in
Biomarkers
/ Biopsy
/ Cancer
/ Cancer therapies
/ Care and treatment
/ Chemotherapy
/ Dehydrogenases
/ Disease susceptibility
/ Gene expression
/ Genes
/ Genetic aspects
/ Genetic transcription
/ Hepatoma
/ Inhibitor drugs
/ Liver cancer
/ Magnetic resonance imaging
/ Medical research
/ Medicine, Experimental
/ Original Paper
/ Patients
/ Platelet-derived growth factor
/ Targeted cancer therapy
/ Tumors
2020
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Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
Journal Article
Gene Signature for Sorafenib Susceptibility in Hepatocellular Carcinoma: Different Approach with a Predictive Biomarker
2020
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Overview
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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