Abstract 5852: Vimentin content associated with shear wave speed in hepatocellular carcinoma: Non-invasive identification of more aggressive tumor phenotypes

Abstract

Abstract Tumor stromal heterogeneity can negatively impact immune surveillance and treatment outcomes. Current cross-sectional imaging tools rely solely on tumor size and perfusion to monitor therapy and fail to characterize tumor biomechanics. Shear-wave elastography has emerged as a non-invasive technique that can quantify stromal elasticity. The goal of the present study is to characterize the molecular underpinnings associated with shear wave elastography measurements in liver cancer. To this end, rat hepatoma cell line McA-RH7777 stably expressing green fluorescent protein genes (fluc/GFP) were implanted in the left liver lobe of Buffalo rats. Three weeks after tumor implantation, adequate tumor size was verified by B-mode ultrasound. A 7-color panel was developed to assess the percentage of vimentin, α-smooth muscle actin, IBA-1, S100A4, TGF-β, and glial fibrillary acidic protein (GFAP) in tumor sections. Shear wave elastography data was used to stratify tumor nodules as stiff or soft according to the mean value of the shear wave (3.05 versus 2,26 m/s). Our results showed two distinct tumor phenotypes. Stiffer tumors, as determined by higher shear wave speed measurements on ultrasound, were characterized by higher percentages of vimentin-positive cells, low S100A4 and IBA-1 macrophages expressing TGF-b, and intermediate expression of IBA-1 macrophages and GFAP cells. Slow shear wave speed, characteristic of softer tumors, displayed the opposite phenotype (two-factor ANOVA; P≤0.001). The most remarkable difference between stiffness phenotypes was the percentage of cells expressing vimentin, with a mean percentage in stiffer tumors of 26.54 compared with 13.68% in softer tumors (P<0.003). Our results indicate that high expression of vimentin is highly correlated with increased shear wave speeds. Given the association between vimentin expression and epithelial-mesenchymal transition a marker of aggressive characteristics of tumor cells (increased migration and invasion), our findings suggest that longitudinal quantification of shear wave speed can be useful to assess functional changes in the stromal component and identify more aggressive tumor phenotypes with a higher likelihood of metastatic potential. Citation Format: Andrea C. Cortes, Kiyoyuki Minamiguchi, Patricia L. Da Costa Lopez, Simone Anfossi, Williams Malea L, Maria S. Stenkamp, Rony Avritscher, Natalie W. Fowlkes. Vimentin content associated with shear wave speed in hepatocellular carcinoma: Non-invasive identification of more aggressive tumor phenotypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5852.