Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation

• Published in: European radiology Vol. 29; no. 5; pp. 2272 - 2282
• Main Authors: Dong, Zhi, Huang, Kun, Liao, Bing, Cai, Huasong, Dong, Yu, Huang, Mengqi, Zhou, Xiaoqi, Jia, Yingmei, Xu, Ling, Luo, Yanji, Li, Zi-Ping, Feng, Shi-Ting
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2019; Springer Nature B.V
• Subjects: Acids; Adult; Aged; Antineoplastic Agents - therapeutic use; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Contrast Media; Diagnostic Radiology; Feasibility Studies; Female; Gadolinium DTPA; Gene expression; Gene therapy; Hepatocellular carcinoma; Homogeneity; Humans; Image contrast; Image enhancement; Image Enhancement - methods; Imaging; Inhibitor drugs; Internal Medicine; Interventional Radiology; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Magnetic Resonance; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Materials selection; Medical imaging; Medicine; Medicine & Public Health; Middle Aged; Neuroradiology; NMR; Nuclear magnetic resonance; Patients; Preoperative Period; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins c-raf - genetics; Radiology; Regression analysis; Retrospective Studies; Risk analysis; Risk Factors; Sorafenib - therapeutic use; Targeted cancer therapy; Tumors; Ultrasound; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-3 - genetics; Vascular endothelial growth factor receptors; Vessels; Hepatocellular carcinoma; Gadoxetic acid; Magnetic resonance imaging; Gene therapy
• ISSN: 0938-7994; 1432-1084
• DOI: 10.1007/s00330-018-5882-4

Purpose To investigate the feasibility of prediction for targeted therapy-related gene expression in hepatocellular carcinoma (HCC) using preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI). Materials and methods Ninety-one patients (81 men, mean age 53.9 ± 12 years) with solitary HCC who underwent preoperative enhanced MRI were retrospectively analyzed. Features including tumor size, signal homogeneity, tumor capsule, tumor margin, intratumoral vessels, peritumor enhancement, peritumor hypointensity, signal intensity ratio on DWI, T1 relaxation times, and the reduction rate between pre- and post-contrast enhancement images were assessed. The operation and histopathological evaluation were performed within 2 weeks after MRI examination (mean time 7 days). The expression levels of BRAF, RAF1 , VEGFR2 , and VEGFR3 were evaluated. The associations between these imaging features and gene expression levels were investigated. Results Tumor incomplete capsules or non-capsules ( p  = 0.001) and intratumoral vessels ( p  = 0.002) were significantly associated with BRAF expression, and tumor incomplete capsules or non-capsules ( p  = 0.001) and intratumoral vessels ( p  = 0.013) with RAF1 expression. There was no significant association between the expression of VEGFR2 , VEGFR3 , and all examined MRI features. Multivariate logistic regression showed that incomplete tumor capsule ( p  = 0.002) and non-capsule ( p  = 0.004) were independent risk factors of HCC with high BRAF expression; incomplete tumor capsule ( p  < 0.001) and non-capsule ( p  = 0.040) were independent risk factors of HCC with high RAF1 expression. Conclusion The presence of incomplete capsule or intratumoral vessels and the absence of capsule are potential indicators of high BRAF and RAF1 expression. Gadoxetic acid–enhanced MRI may facilitate the choice of gene therapy for patients with HCC. Key Points • Incomplete tumor capsule and non-capsule were independent risk factors of HCC with high BRAF and RAF1 expression. • The presence of intratumoral vessels was a potential indicator of high BRAF and RAF1 expression. • Gadoxetic acid-enhanced MRI may be a predictor of efficacy of treatment with sorafenib.