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Recent investigations have highlighted the significant roles of inflammation and aging in the progression of non-viral liver cancers. Among these, the consumption of green tea has emerged as a promising avenue for mitigating some of the pathways involved in the disease’s development, alongside other therapeutic options.
Liver cancer can occur spontaneously in healthy liver tissues; however, a concerning trend has emerged linking certain liver cancers with non-viral chronic liver disease (CLD). Research indicates that hepatocellular carcinoma (HCC), a common form of liver cancer, is associated with CLD in approximately 15-25% of instances. Enhanced awareness and screening have led to earlier detection of liver cancer, which is crucial for successful treatment. Nevertheless, the focus on preventing cancer remains a top priority for healthcare professionals and researchers alike.
The rising incidence of CLD among patients with HCC raises questions about how this condition predisposes liver tissues to cancerous transformations. To explore the differences between healthy liver tissue and that affected by HCC in the context of CLD, scientists from Hiroshima University and affiliated institutions conducted a study comparing gene expression and metabolic profiles. Their findings were published on February 21 in the Journal of Proteome Research.
“Our study focused on analyzing non-cancerous liver tissues near HCC lesions from patients suffering from non-viral chronic liver disease. Through comprehensive multi-omics analysis, including transcriptomic and metabolomic data, we aimed to elucidate the molecular mechanisms that result in HCC and pinpoint new targets for preventive measures,” stated Hikaru Nakahara, a graduate student at Hiroshima University and the lead author of the study.
To achieve their goals, the research team employed RNA sequencing to investigate RNA transcripts, assessing which genes were active in both normal and CLD-affected tissues. By measuring the abundance of each RNA transcript, they were able to identify variations in gene expression and deduce the cellular pathways involved in the disease process.
Additionally, the team examined the metabolites present in both CLD and healthy tissues to detect dysregulated metabolic pathways. By comparing these aspects, they identified potential pathways that may drive disease progression and explore possible therapeutic targets for HCC prevention.
“Our findings indicate that the mechanisms leading to HCC from CLD are linked to the activation of inflammatory signals and metabolic issues related to aging. It is crucial to identify chemoprevention targets that reflect these distinct mechanisms,” commented Atsushi Ono, a lecturer at Hiroshima University and co-author of the research. He also noted that antioxidant supplementation, particularly with epigallocatechin gallate (EGCG), could be beneficial in addressing these metabolic disturbances.
The research team classified cases of CLD into two subtypes: Subtype 1, which shows heightened inflammatory activity, and Subtype 2, characterized by an older patient demographic. Previous studies have suggested that the aggravated inflammatory signaling in Subtype 1 may contribute to cancer risk. Interestingly, both subtypes exhibited diminished gene expression linked to fatty acid metabolism, with Subtype 2 showcasing an accumulation of fatty acids and metabolite deficiencies compared to healthy liver tissue.
Exploring Green Tea’s Impact and Other Potential Therapies
Dysregulation in the cellular pathways associated with CLD presents critical opportunities for therapeutic intervention in HCC prevention. The researchers investigated the effects of various treatments on gene expression patterns seen in the CLD subtypes. A related study using a mouse model of diet-induced non-alcoholic fatty liver indicated that green tea or EGCG substantially inhibited the heightened expression of inflammatory pathways. Hence, EGCG could play a role in reversing some of the pathway dysfunctions that contribute to HCC development.
While the current findings are promising, the research team emphasizes that further studies are necessary to establish the effectiveness of potential HCC preventive therapies. “In the future, we envision treatments tailored to the specific molecular abnormalities present, such as targeting inflammation in the CLD group with elevated inflammatory markers, or restoring metabolite levels that decline with age in the aging-related CLD group,” concluded Ono.
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