RAF1 Expression is Correlated with HAF, a Parameter of Liver Computed Tomographic Perfusion, and may Predict the Early Therapeutic Response to Sorafenib in Advanced Hepatocellular Carcinoma Patients

Ninzi Tian; Dong Wu; Ming Tang; Huichuan Sun; Yuan Ji; Cheng Huang; Lingli Chen; Gang Chen; Mengsu Zeng

doi:10.1515/med-2020-0024

RAF1 Expression is Correlated with HAF, a Parameter of Liver Computed Tomographic Perfusion, and may Predict the Early Therapeutic Response to Sorafenib in Advanced Hepatocellular Carcinoma Patients

Open Med (Wars). 2020 Mar 8:15:167-174. doi: 10.1515/med-2020-0024. eCollection 2020.

Authors

Ninzi Tian^{1

2}, Dong Wu^{1

2}, Ming Tang^{2

1}, Huichuan Sun³, Yuan Ji⁴, Cheng Huang³, Lingli Chen⁴, Gang Chen^{2

1}, Mengsu Zeng^{2

1}

Affiliations

¹ Department of Radiology, Zhongshan Hospital of Fudan University, 180 Fenglin Rd, Xuhui District, Shanghai 200032, China.
² Shanghai Institute of Medical Imaging, Shanghai Medical College, Fudan University, Shanghai 200032, China.
³ Department of Liver Surgery, Zhongshan hospital of Fudan University, Shanghai 200032, China.
⁴ Department of Pathology, Zhongshan hospital of Fudan University, Shanghai 200032, China.

Abstract

Objectives: Monitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.

Methods: A total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.

Results: According to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.

Conclusion: RAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

Keywords: Hepatocellular carcinoma; Liver computed tomography perfusion; Sorafenib.