A Novel Correlation of Preoperative Gd-EOB-DTPA-contrast-enhanced MRI with FGFR4 Expression and Its Value in Targeted Therapy for Hepatocellular Carcinoma

Abstract Purpose: To assess the relationship between preoperative gadolinium ethoxy-benzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) features and fibroblast growth factor receptor 4 (FGFR4) gene expression in hepatocellular carcinoma (HCC). Materials and methods: Fifty-nine HCC patients (54 males, 5 females) who underwent preoperative enhanced MRI were retrospectively enrolled in this study. Quantitative and qualitative features of Gd-EOB-DTPA-enhanced MRI were analyzed in these pathologically confirmed HCC patients. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were performed to determine the mRNA and protein levels of FGFR4 in HCC. The relationship between these image features and the level of FGFR4 gene expression in HCC was evaluated by correlation analysis. Results: The FGFR4 mRNA and protein expression has significant correlation with the change of signal intensity in the phase of hepatobiliary, IHC analysis revealed significant correlation between the protein expression of FGFR4 and the qualitative enhanced MRI feature, mainly the manifestation of the intratumoral vessels at the arterial phase. Furthermore, the presence of intratumoral vessels (P =0.034, OR=4.71) and heterogeneous 3 signal performance in the hepatobiliary phase (P =0.008, OR=4.2) were identified as independent indicators for high FGFR4 expression in HCC. Conclusions: The findings demonstrate novel correlation between enhanced MRI features and FGFR4 gene expression, suggesting the heterogeneous signal intensity at the phase of hepatobiliary and the present of intratumoral vessels in the arterial phase as indicators for high FGFR4 expression in HCC. Our study may have clinical implication that enhanced MRI holds promise as useful modality in treatment selection of targeted therapies to HCC patients.