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

Zhi Dong, Kun Huang, Bing Liao, Huasong Cai, Yu Dong, Mengqi Huang, Xiaoqi Zhou, Yingmei Jia, Ling Xu, Yanji Luo, Zi Ping Li, Shi Ting Feng

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)2272-2282
Number of pages11
JournalEuropean Radiology
Volume29
Issue number5
DOIs
Publication statusPublished - 1 May 2019

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Capsules
Hepatocellular Carcinoma
Magnetic Resonance Imaging
Gene Expression
Neoplasms
Image Enhancement
sorafenib
Genetic Therapy
Logistic Models

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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. / Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma : preoperative MRI and histopathological correlation. In: European Radiology. 2019 ; Vol. 29, No. 5. pp. 2272-2282.
@article{746125231d254db788b578945c8f1187,
title = "Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation",
abstract = "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.",
keywords = "Gadoxetic acid, Gene therapy, Hepatocellular carcinoma, Magnetic resonance imaging",
author = "Zhi Dong and Kun Huang and Bing Liao and Huasong Cai and Yu Dong and Mengqi Huang and Xiaoqi Zhou and Yingmei Jia and Ling Xu and Yanji Luo and Li, {Zi Ping} and Feng, {Shi Ting}",
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Dong, Z, Huang, K, Liao, B, Cai, H, Dong, Y, Huang, M, Zhou, X, Jia, Y, Xu, L, Luo, Y, Li, ZP & Feng, ST 2019, 'Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation' European Radiology, vol. 29, no. 5, pp. 2272-2282. https://doi.org/10.1007/s00330-018-5882-4

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

In: European Radiology, Vol. 29, No. 5, 01.05.2019, p. 2272-2282.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma

T2 - preoperative MRI and histopathological correlation

AU - Dong, Zhi

AU - Huang, Kun

AU - Liao, Bing

AU - Cai, Huasong

AU - Dong, Yu

AU - Huang, Mengqi

AU - Zhou, Xiaoqi

AU - Jia, Yingmei

AU - Xu, Ling

AU - Luo, Yanji

AU - Li, Zi Ping

AU - Feng, Shi Ting

PY - 2019/5/1

Y1 - 2019/5/1

N2 - 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.

AB - 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.

KW - Gadoxetic acid

KW - Gene therapy

KW - Hepatocellular carcinoma

KW - Magnetic resonance imaging

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U2 - 10.1007/s00330-018-5882-4

DO - 10.1007/s00330-018-5882-4

M3 - Article

VL - 29

SP - 2272

EP - 2282

JO - European Radiology

JF - European Radiology

SN - 0938-7994

IS - 5

ER -