Prediction of sorafenib treatment–related gene expression for hepatocellular carcinoma: preoperative MRI and histopathological correlation
- 54 Downloads
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.
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.
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.
• 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.
KeywordsMagnetic resonance imaging Hepatocellular carcinoma Gene therapy Gadoxetic acid
Apparent diffusion coefficient
Percentage of decrease in T1 relaxation time in the hepatocellular phase
T1 Relaxation time in the hepatocellular phase
T1 Relaxation time on non-enhanced scan
Vascular endothelial growth factor receptor
Volume interpolated breath-hold examination
This work was funded by the National Natural Science Foundation of China (81771908, 81571750, 81770654).
Compliance with ethical standards
The scientific guarantor of this publication is Zi-Ping Li.
Conflict of interest
The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.
Statistics and biometry
One of the authors has significant statistical expertise.
Written informed consent was obtained from all subjects (patients) in this study.
Institutional Review Board approval was obtained.
• performed at one institution
- 1.Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108Google Scholar
- 7.Burrell RA, Mcgranahan N, Bartek J, Swanton C (2013) The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501(7467):338–345Google Scholar
- 8.Bedard PL, Hansen AR, Ratain MJ, Siu LL (2013) Tumour heterogeneity in the clinic. Nature 501(7467):355–364Google Scholar
- 17.Stigliano R, Marelli L, Yu D, Davies N, Patch D, Burroughs AK (2007) Seeding following percutaneous diagnostic and therapeutic approaches for hepatocellular carcinoma. What is the risk and the outcome? Seeding risk for percutaneous approach of HCC. Cancer Treat Rev 33(5):437–447Google Scholar
- 18.Silva MA, Hegab B, Hyde C, Guo B, Buckels JA, Mirza DF (2008) Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut 57(11):1592–1596Google Scholar
- 19.Ahn SS, Kim MJ, Lim JS, Hong HS, Chung YE, Choi JYl (2010) Added value of gadoxetic acid-enhanced hepatobiliary phase MR imaging in the diagnosis of hepatocellular carcinoma. Radiology 255(2):459–466Google Scholar
- 22.Thaiss WM, Kaufmann S, Kloth C, Nikolaou K, Bösmüller H, Horger M (2016) VEGFR-2 expression in HCC, dysplastic and regenerative liver nodules, and correlation with pre-biopsy dynamic contrast enhanced CT. Eur J Radiol 85(11):2036–2041Google Scholar
- 23.Purysko AS, Remer EM, Coppa CP, Leão Filho HM, Thupili CR, Veniero JC (2012) LI-RADS: a case-based review of the new categorization of liver findings in patients with end-stage liver disease. Radiographics 32:1977–1995Google Scholar
- 32.Wang B, Ding YM, Fan P, Wang B, Xu JH, Wang WX (2014) Expression and significance of MMP2 and HIF-1alpha in hepatocellular carcinoma. Oncol Lett 8(2):539–546Google Scholar
- 39.Huang Z, Meng X, Xiu J et al (2014) MR imaging in hepatocellular carcinoma: correlations between MRI features and molecular marker VEGF. Med Oncol 31(12):313Google Scholar