Published online Sep 28, 2022. doi: 10.3748/wjg.v28.i36.5250
Peer-review started: March 9, 2022
First decision: April 11, 2022
Revised: April 30, 2022
Accepted: August 16, 2022
Article in press: August 16, 2022
Published online: September 28, 2022
Processing time: 197 Days and 22 Hours
Transforming growth factor-beta (TGF-β) is a multifunctional cytokine that performs a dual role as a tumor suppressor and tumor promoter during cancer progression. Among different ligands of the TGF-β family, TGF-β1 modulates most of its biological outcomes. Despite the abundant expression of TGF-β1 in the liver, steatosis to hepatocellular carcinoma (HCC) progression triggers elevated TGF-β1 levels, contributing to poor prognosis and survival. Additionally, elevated TGF-β1 levels in the tumor microenvironment create an immunosuppressive stage via various mechanisms. TGF-β1 has a prime role as a diagnostic and prognostic biomarker in HCC. Moreover, TGF-β1 is widely studied as a therapeutic target either as monotherapy or combined with immune checkpoint inhibitors. This review provides clinical relevance and up-to-date information regarding the potential of TGF-β1 in diagnosis, prognosis, and therapy against HCC.
Core Tip: Transforming growth factor-beta 1 (TGF-β1) exhibits a progressive elevation throughout hepatic dysfunction starting from hepatitis to hepatocellular carcinoma (HCC) as an inflammatory cytokine, pro-fibrogenic marker, immunosuppressive agent and pro-carcinogenic growth factor. Aberrant TGF-β1 activation in HCC is associated with poor prognosis and survival. TGF-β1 mediated immunosuppression disturbs the anticancer surveillance and the efficacy of the immunotherapeutic agent. This pleiotropic effect of TGF-β1 in the context of HCC makes it ideal as a diagnostic, prognostic, and therapeutic candidate in HCC.