Abstract 3379: Multi-cohort study shows HCC is associated with a relative regional reduction in TGFBR2 in liver biopsies from patients with cirrhosis

Abstract

Abstract Background: Early detection of hepatocellular carcinoma (HCC) is challenging partly because most patients also have cirrhosis. Furthermore, patients with cirrhosis are at high risk of developing HCC. Loss of function of the transforming growth factor β (TGF-β) pathway is associated with HCC. The goal of this study was to determine if a reduction in TGF-β receptors (TGFBR1, TGFBR2) was able to reliably and reproducibly predict HCC in cirrhotic tissue. Methods: We performed quantitative immunohistochemical (IHC) analysis of biopsy tissue from patients with cirrhosis with or without HCC using 3 separate sets of samples. We developed an automated image analysis pipeline to quantify IHC of TGFBR1 and TGFRB2 in liver biopsies. Using logistic regression modeling, we evaluated the predictive power of staining intensity of TGFBR1, TGFBR2, or the combination in differentiating HCC from cirrhosis. Results: We found a consistently significant reduction in TGFBR2 in HCC (p < 0.02) among independent patient cohorts from 3 separate institutions. With the data, we developed an artificial intelligence-based image analysis pipeline that confirmed the significant reduction in TGFBR2 staining intensity in HCC compared to cirrhotic tissue (p < 0.002). Unfortunately, logistic regression modeling of the quantitative data showed that there is not a simple threshold of TGFBR2 staining intensity that is diagnostic of HCC. Instead, in 84% of samples with HCC, HCC was associated with a relative regional reduction in TGFBR2 compared to tumor-adjacent cirrhotic tissue. Conclusions: The qualitative and quantitative analyses indicate that evaluating biopsy samples for a reduction in TGFBR2 abundance relative to the surrounding cirrhotic tissue could be an early indicator of the development of HCC in high-risk groups undergoing surveillance for HCC. Furthermore, an automated image analysis pipeline for quantitative IHC of TGFBR staining could improve the reliability of image analysis across institutions participating in clinical trials. Citation Format: Krishanu Bhowmick, Richard Amdur, Xiyan Xiang, Herbert Yu, Linda L. Wong, Shuyun Rao, Aiwu R. He, Karan Amin, Daewa Zaheer, Raj K. Narayan, Sanjaya K. Satapathy, Chandan Guha, Patricia S. Latham, Kirti Shetty, Nancy R. Gough, Lopa Mishra. Multi-cohort study shows HCC is associated with a relative regional reduction in TGFBR2 in liver biopsies from patients with cirrhosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3379.