Volume 154, Issue 1, Pages 17-20 (January 2018) The Role of Transforming Growth Factor-β in Human Hepatocarcinogenesis: Mechanistic and Therapeutic Implications From an Integrative Multiomics Approach  Jens U. Marquardt  Gastroenterology  Volume 154, Issue 1, Pages 17-20 (January 2018) DOI: 10.1053/j.gastro.2017.11.015 Copyright © 2018 AGA Institute Terms and Conditions

Figure 1 Clinical impact of transforming growth factor beta (TGF-β) alterations in human liver cancer. Hepatocellular carcinoma (HCC) is a molecularly heterogeneous disease. The study by Chen et al7 demonstrates the existence of numerous alterations in TGF-β pathway driving progression of molecularly diverse HCC. Activation of TGF-β signaling is commonly associated with enrichment of immunogenic and oncogenic signaling pathways and a better prognosis as compared with HCC characterized by inhibition of the tumor-suppressive properties of TGF-β signaling, leading to oxidative stress and repression of DNA repair mechanisms, thereby increasing mutational load. In particular, the SPTBN1-D1089Y mutation caused inhibition of functional TGF-β/SMAD3 signaling and a consecutive loss of TGF-β tumor suppressive function. The distinct TGF-β–dependent biological traits identified in this study might provide a promising approach for selection of patients with HCC who are most likely to benefit from the specific therapies. Patients with HCC with activated TGF-β signaling might be responsive to immunotherapeutic intervention as well as to a target inhibition of TGF-β and other key oncogenes. The patients with HCC lacking TGF-β tumor suppressive function might be sensitive to conventional chemotherapy using DNA cross-linking agents or irradiation. Gastroenterology 2018 154, 17-20DOI: (10.1053/j.gastro.2017.11.015) Copyright © 2018 AGA Institute Terms and Conditions