<p>Gut Microbiota, Peroxisome Proliferator-Activated Receptors, and Hepatocellular Carcinoma</p>

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. HCC incidence rate is sixth and mortality is fourth worldwide. However, HCC pathogenesis and molecular mechanisms remain unclear. The incidence of HCC is associated with genetic, environmental, and metabolic factors. The role of gut microbiota in the pathogenesis of HCC has attracted researchers’ attention because of anatomical and functional interactions between liver and intestine. Studies have demonstrated the involvement of gut microbiota in the development of HCC and chronic liver diseases, such as alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and liver cirrhosis. Peroxisome proliferator-activated receptors (PPARs) are a group of receptors with diverse biological functions. Natural and synthetic PPAR agonists show potential for treatment of NAFLD, liver fibrosis, and HCC. Recent studies have demonstrated that PPARs take part in gut microbiota inhabitation and adaptation. This manuscript reviews the role of gut microbiota in the development of HCC and precancerous diseases, the role of PPARs in modulation of gut microbiota and HCC, and potential of gut microbiota for HCC diagnosis and treatment.

Systematic Construction and Validation of a Prognostic Model for Hepatocellular Carcinoma Based on Immune-Related Genes

“…PPARs, nuclear hormone receptors, could be activated by fatty acids and their derivatives and PPAR agonists are beneficial for the treatment of non-alcoholic fatty liver disease (NAFLD), liver fibrosis, and HCC ( Cao et al, 2009 ). Recent, studies demonstrated that PPARs participate in the progression of gut microbiota inhabitation and adaptation which is related to the pathogenesis of HCC ( Yu et al, 2020 ). These signaling pathways were shown to be associated with HCC progression in our analysis and were consistent with those reported in published literature.…”

Episodic Detectable Viremia Does Not Affect Prognosis in Untreated Compensated Cirrhosis With Serum Hepatitis B Virus DNA <2,000 IU/mL

“…AVT with potent oral nucleos(t)ide analogs (NUCs), such as entecavir or tenofovir disoproxil fumarate, can lead to virological and biochemical remission and prevent disease progression to hepatocellular carcinoma (HCC) and/or liver cirrhosis (1–4). HBV induces carcinogenesis via multiple pathways, and it is difficult to eradicate the risk of HCC, which remains a major issue from the perspective of public health and socioeconomic burden (5–11). Therefore, along with effective AVT, periodic surveillance is required to detect early-stage HCC and allow timely interventions with a curative intent (2,12–14).…”

Gut microbiota and immune system in liver cancer: Promising therapeutic implication from development to treatment

“…The pathways involving the peroxisome proliferator-activated receptors (PPARs) could have a role in the HCC development. Published data reported their protective role in chronic liver disease development through an interplay with the microbiome and their ability to reverse leaky gut conditions and dysbiosis[ 65 ].…”

“…Although specific studies on cancer progression are lacking, targeting the PPARs could represent, at least, a cancer prevention strategy. Further details can be found elsewhere[ 65 ].…”