Construction of an Oxidative Stress Risk Model to Analyze the Correlation Between Liver Cancer and Tumor Immunity.

BACKGROUND: Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Despite advancements in immunotherapy, the prognosis for patients with HCC continues to be poor. As oxidative stress plays a significant role in the onset and progression of various diseases, including metabolism-related HCC, comprehending its mechanism in HCC is critical for effective diagnosis and treatment. METHODS: This study utilized the TCGA dataset and a collection of oxidative stress genes to determine the expression of oxidative stress-related genes in HCC and their association with overall survival using diverse bioinformatics methods. A novel prognostic risk model was developed, and the TCGA cohort was divided into high-risk and low-risk groups based on each tumor sample's risk score. Levels of immune cell infiltration and the expression of immune checkpoint-related genes in different risk subgroups were analyzed to investigate the potential link between tumor immunity and oxidative stress-related features. The expression of model genes in actual samples was validated through immunohistochemistry, and their mRNA and protein expression levels were measured in cell cultures. RESULTS: Four oxidative stress-related genes (EZH2, ANKZF1, G6PD, and HMOX1) were identified and utilized to create a predictive risk model for HCC patient overall survival, which was subsequently validated in an independent cohort. A significant correlation was found between the expression of these prognostic genes and the infiltration of tumor immune cells. Elevated expression of EZH2, ANKZF1, G6PD, and HMOX1 was observed in both HCC tissues and cell lines. CONCLUSION: The combined assessment of EZH2, ANKZF1, G6PD, and HMOX1 gene expression can serve as a model to evaluate the risk of oxidative stress in HCC. Furthermore, there is a notable correlation between the expression of these risk model genes and tumor immunity.

The Role of Oxidative Stress in the Development and Therapeutic Intervention of Hepatocellular Carcinoma.

Oxidative stress (OS) is a condition in which the body has an unbalanced oxidative and antioxidant effect. Oxidative stress has emerged as a critical component in the onset and progression of numerous diseases, including liver cancer and chronic liver disease caused by the hepatitis C virus and hepatitis B virus. Reactive oxygen species (ROS) are the most prevalent reactive chemical species involved in the oxidative stress response during the progression of the disease. Oxidative stress has a unique role in the development of hepatocellular carcinoma (HCC), and excessive ROS production is a common occurrence in liver illnesses of various etiologies. In response to various deleterious stimuli, the liver shows manifestations of lipid accumulation, oxidative damage, inflammatory infiltration, and immune response, which interact with each other in a mutually reinforcing manner, collectively exacerbating liver damage and malignant transformation. The intracellular buildup of ROS is a two-edged sword for tumor advancement. ROS are tumorigenic, and low amounts of ROS can trigger different signaling pathways that promote proliferation, survival, and migration, among other aspects. However, excessive oxidative stress can induce tumor cell death. Understanding the mechanisms of oxidative stress in hepatocellular carcinogenesis is beneficial for the prevention and surveillance of hepatocellular carcinoma in humans. An improved knowledge of the impacts and potential implications of oxidative stress regulation in therapeutic strategies will likely allow us to find new therapeutic targets for cancer. Oxidative stress also plays a significant role in the treatment of hepatocellular carcinoma and the mechanisms of drug resistance involved. This paper reviews recent studies on oxidative stress in HCC that are more reliable and important, and provides a more comprehensive view of the development of the treatment of HCC based on the relevant summaries of the effect of oxidative stress on the treatment.

Cadherin-16 inhibits thyroid carcinoma cell proliferation and invasion.

Cadherin-16 (CDH16), a member of the cadherin family of adhesion molecules, serves an important role in the formation and maintenance of the thyroid follicular lumen. Decreased expression of CDH16 has been reported to be associated with tumor stage in papillary thyroid cancer (PTC); however, previous analyses have been limited and the biological role of CDH16 in different subtypes of TC is unknown. To investigate the role of CDH16 in the occurrence and development of TC, bioinformatic analysis of three TC subtypes (PTC, follicular cell-derived TC and anaplastic TC) was performed using an extended data set from the Gene Expression Omnibus database, with additional confirmation using data from The Cancer Genome Atlas, as well as biopsies from 35 patients with PTC and TC or follicular cell lines. According to the dataset analysis, CDH16 was downregulated in PTC and follicular cell-derived and anaplastic TC; the downregulation in PTC was independent of DNA copy number variation. Furthermore, low expression levels of CDH16 were significantly correlated with tumor size, lymph node metastasis status and disease stage in 35 patients with PTC. Gene Set Enrichment Analysis suggested that CDH16 participated in DNA replication and cell adhesion pathways. To evaluate CDH16 activity, CDH16 was overexpressed in TC-derived BCPAP cells. CDH16 overexpression inhibited cell proliferation, migration and invasion and induced apoptosis by downregulating proteins associated with DNA replication and cell adhesion. These results support the identification of CDH16 as a valuable target for TC prognosis and therapy and, to the best of our knowledge, represent the first direct demonstration of its mechanistic role in TC.