title: An investigation of the role of gene copy number variations in sorafenib sensitivity in metastatic hepatocellular carcinoma patients.
abstract: Background: Metastatic hepatocellular carcinoma (HCC) is a highly aggressive tumor with limited treatment options. While sorafenib has recently been shown to provide a survival advantage in patients with advanced HCC, the overall outcomes such as time to progression (TTP) and overall survival (OS) ought to be further improved. To that end, several targeted agents aimed at amplified oncogenes such asHER2andFGFR2have recently been developed. In this study, we aimed to identify genetic markers in the form of copy number variations (CNVs) that influence clinical outcomes post-sorafenib treatment in advanced HCC patients.Methods:We surveyed 38 metastatic HCC patients who were treated with sorafenib for the presence of CNVs using the NanoString nCounter assay.Results:The median TTP and OS for all patients were 2.7 months (95% confidence interval [CI]: 2.0-3.3 months) and 13.4 months (95% CI: 8.4-18.4 months), respectively. Several genes previously implicated in liver cancer were amplified, includingCCND1(n = 4),CDKN1A(n = 2),KRAS(n = 2),MDM2(n = 1), andERBB2(n = 1). However, we found no correlations between CNVs and survival in our sorafenib-treated patients.Conclusions:The clinical features and biomarkers that account for sensitivity to sorafenib in HCC are complicated and remain unclear. Further investigation to identify predictive biomarkers and therapeutic strategies, including combining sorafenib with other target agents, are warranted.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea;; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ji Yun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Center for Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea;; Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Mineui
authors.initials: M
authors.lastname: Hong
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Center for Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Seoul, Korea;; Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Cheolkeun
authors.initials: C
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
keywords: Hepatocellular carcinoma; copy number variations; metastatic disease; sorafenib.