The liver is a shocking organ that regulates our body’s metabolism and detoxifies our blood. The liver is made from several different cell types that work professionally, and when we are healthy, each cell does a great job, and the entire organ works like an oiled robot. Sometimes, when the disease affects the liver, cells no longer perform their work well and undergo what is called transformation. This blurs the boundaries between the different types of cells that make up our liver and the machine booth, making it impossible for our liver to perform its important work. As more and more cells transform, one or both of the two types of cancers are more likely to develop: hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). HCC is the more common HCC in both rooted in a range of chronic liver conditions, from viral hepatitis to metabolic syndrome. On the other hand, CCA, while not so common, casts shadows with a severe survival rate. At the heart of the battle between these two cancers is a molecular switch controlled by the oncogene MYC, which determines the cell’s allegiance to HCC or CCA, affected by the transcription factor (TFS), which is invisible to the fate of the cell Master of puppets.
Led by Dr. Amanda Craig and Dr. Xin Wei Wang of the National Cancer Institute (NIH), a pioneering study published in the Cell Reports, delving into the genetic complexity of primary liver cancer. The research team used single-cell assay to perform transposase-accessible chromatin sequencing (SCATAC-SEQ) and began to explore the transcriptional kinetics (HCC) and intrahepatic cholangiocarcinoma (ICCA) of hepatic cell carcinoma (HCC) (HCC). , different transcription factor (TF) isoforms that characterize these characteristics.
Primary liver cancer is mainly divided into hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICCA). The role of transcription factors (TFS) in guiding malignant progression between HCC and ICCA is not fully understood. “Dr. Craig clarified. Through a detailed analysis of chromatin characteristics of patient cells, the study depicts a comprehensive picture of the cell composition in liver cancer and determines the TF that distinguishes HCC from ICCA, thus elucidating its unique genetic regulation mechanism.
“To delve into chromatin accessibility and genetic regulation of primary liver cancer, we performed SCATAC-SEQ in selected patients, mainly patients with HCC and a small number of patients with ICCA. We evaluated thousands of patients with passes Our rigorous quality-examined chromatin accessibility profiles in cells. “The insights gained from this study not only improve our understanding of the liver cancer gene framework, but also highlight the prognostic importance of the POU TF family in ICCA, will Its presence is linked to adverse patient outcomes.
“In our analysis, the POU TF family showed extensive expression in liver tumors. The presence of the POU TF family is more pronounced in tumors with TP53 mutations and is significantly associated with reduced survival.” Dr. Craig further Explain.
Despite significant progress in treatment, liver cancer remains the leading cause of cancer-related mortality worldwide. Dr. Craig and colleagues stressed the urgent need to reveal different developments in these malignant tumors to enhance therapeutic efficacy. Their study elucidates various transcriptional landscapes in liver cancer, demonstrating the specific role of nuclear receptors and ETS transcription factor families in distinguishing from ICCA. Although certain families of transcription factor are prevalent in both HCC and ICCA, their association with prognostic factors is subtype-specific, suggesting that their effect on cancer progression depends on specific cellular characteristics. The findings of Dr. Craig and her team provide valuable insight into the transcriptional mechanisms that drive liver cancer, suggesting that potential therapeutic targets may have a positive impact on patient outcomes. Future studies are expected to explore therapeutic vulnerabilities associated with abnormal transcription factor activity, marking a significant step in personalized treatment for patients with liver cancer.
Journal Reference
Craig et al., “Genome-wide analysis of transcription factor activity in primary liver cancer using single-cell ATAC sequencing”, Cell report.
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