Liver cell carcinoma introduction and significance

Answer from top 10 papers

Liver cell carcinoma, also known as hepatocellular carcinoma (HCC), is a primary malignant neoplasm of the liver, originating from epithelial cells. It is recognized as one of the most common cancers globally and ranks as the third leading cause of cancer-related mortality (Song et al., 2021). The significance of HCC is underscored by its aggressive nature, rapid progression, and poor survival prognosis, which necessitates a deeper understanding of its genetic and epigenetic underpinnings for better diagnostic and therapeutic strategies (Kruel et al., 2017).
Interestingly, recent research has highlighted the role of epigenetic changes, including the deregulation of long noncoding RNAs (lncRNAs), in the development and progression of HCC. These lncRNAs can function as tumor suppressors or oncogenes, influencing gene expression through epigenetic mechanisms, which could be considered for targeted therapeutic approaches (Piechota, 2015). Additionally, the heterogeneity of HCC tumors contributes to drug resistance and clinical trial failures, but advancements in single-cell technology (SCT) offer new insights into this heterogeneity, potentially improving diagnosis and treatment (Amicone et al., 2015).
In summary, hepatocellular carcinoma is a significant health concern due to its high prevalence and mortality rate. The complexity of its pathogenesis, involving genetic mutations and epigenetic alterations, presents challenges in management and treatment. However, ongoing research into the molecular mechanisms of HCC holds promise for the development of more effective diagnostic tools and targeted therapies (Kruel et al., 2017; Piechota, 2015; Song et al., 2021).

Source Papers

Inhibition of RFX6 Suppresses Invasive Ability of Tumor Cells and Activates T Cell Immune Response Though Notch Pathway in Hepatocellular Carcinoma

Abstract Background DNA-binding protein RFX6 was overexpressed in hepatocellular carcinoma and its expression level was correlated with the prognosis and immune cell infiltration in liver hepatocellular carcinoma. However, the mechanism of abnormal expression and biological effects of RFX6 in liver cancer remains unknown. Methods To understand the specific expressing mechanism of RFX6 in liver cancer, we performed bioinformatic prediction, CHIP-qPCR assay, Co-IP and dual-luciferase assay to assess the regulating mechanism of RFX6. In the meantime, a series of biological experiments in vivo and vitro were conducted to analyze the biological significance of RFX6 in hepatocellular carcinoma. Results We demonstrated that the knockdown of RFX6 in liver cancer cells significantly suppressed the proliferation, migration and invasion of cancer cells. Moreover, inhibition of RFX6 could stimulate immune response of T cells. Among lots of interacting proteins, we revealed RFX6 directly binding to DTX2, regulator of Notch signaling pathway by targeting NOTCH1, and help it`s transcription stability. Furthermore, we discovered miRNA-542-3p, expression of which was decreased in hepatocellular carcinoma, was directly involved in negative regulation of the expression of RFX6. Conclusions In summary, we discovered a miRNA-542-3p-RFX6-DTX2-NOTCH1 regulatory pathway played significant roles in the tumor progression of liver hepatocellular carcinoma.

Liver Cell Carcinoma in Poland: Data Reported to the National Health Fund in the Years 2008-2012

Introduction: Liver cell carcinoma includes primary malignant liver neoplasms originating from epithelial cells. Liver cell carcinoma is one of the most common cancers and is the 3rd leading cause of cancer-related mortality worldwide. However, the epidemiology and the various available treatment options have not been sufficiently studied in Poland. The aim of the present study was to assess the frequency of use of various liver cell carcinoma treatments in Poland based on data reported by service providers to the National Health Fund in the years 2008-2012. Patients and methods: Data concerning patients with liver cell carcinoma were obtained by querying the National Health Fund databases. The data were collected from the databases using SQL tools and a filter in accordance with the accepted scope of ICD-10 diagnoses. The analysis was conducted using Excel and Statistica 10. The demographic data were collected from the Central Statistical Office’s website. Results: Data on the number of patients and the type of medical services available for patients with a diagnosis of liver cell carcinoma financed by NFZ in the years 2008-2012 are described. Conclusions: The health care system in Poland does not provide liver cell carcinoma patients with rapid access to required health care services, which decreases patient survival. Treatment of advanced stage liver cell carcinoma with Sorafenib, with public payer financing, represents a real and accessible alternative treatment option for this group of patients.

Open Access
An Overview on Single-Cell Technology for Hepatocellular Carcinoma Diagnosis.

Hepatocellular carcinoma is a primary liver cancer caused by the accumulation of genetic mutation patterns associated with epidemiological conditions. This lethal malignancy exhibits tumor heterogeneity, which is considered as one of the main reasons for drug resistance development and failure of clinical trials. Recently, single-cell technology (SCT), a new advanced sequencing technique that analyzes every single cell in a tumor tissue specimen, aids complete insight into the genetic heterogeneity of cancer. This helps in identifying and assessing rare cell populations by analyzing the difference in gene expression pattern between individual cells of single biopsy tissue which normally cannot be identified from pooled cell gene expression pattern (traditional sequencing technique). Thus, SCT improves the clinical diagnosis, treatment, and prognosis of hepatocellular carcinoma as the limitations of other techniques impede this cancer research progression. Application of SCT at the genomic, transcriptomic, and epigenomic levels to promote individualized hepatocellular carcinoma diagnosis and therapy. The current review has been divided into ten sections. Herein we deliberated on the SCT, hepatocellular carcinoma diagnosis, tumor microenvironment analysis, single-cell genomic sequencing, single-cell transcriptomics, single-cell omics sequencing for biomarker development, identification of hepatocellular carcinoma origination and evolution, limitations, challenges, conclusions, and future perspectives.

Open Access
GENETIC MECHANISMS OF HEPATOCELLULAR CARCINOMA:
 LITERATURE REVIEW

Relevance: Hepatocellular carcinoma (HCC) is the most common form of primary liver malignancy. This form of liver cancer is characterized
 by rapid progression and poor survival prognosis. Understanding the genetic mechanisms that underlie HCC is of great importance for
 developing new diagnostic and therapeutic approaches.
 The purpose is to study the genetic factors in the development of hepatocellular carcinoma.
 Materials and methods: This review used various sources of literature, including scientific articles and reviews. We reviewed the results
 of scientific and clinical studies published in 2018-2023 and indexed in the PubMed, Cochrane library, Scopus and Web of Science databases,
 using the keywords “hepatocellular carcinoma,” “genes,” and “genetic predictors.” Inclusion of articles in the review was based on their
 content and relevance to the research topic.
 Results: Various genes associated with hepatocellular carcinoma were analyzed, including genes frequently mutated in HCC, as well
 as genes that play a role in the regulation of cell growth, apoptosis, metastasis, and invasion. Epigenetic changes such as DNA methylation
 and chromatin modifications have been investigated. The roles of microRNAs, long non-coding RNAs, circulating microparticles and other
 biomarkers in the diagnosis and prognosis of HCC were also reviewed.
 Conclusion: The materials and methods used in this review allowed us to cover a wide range of genes and molecular mechanisms associated
 with hepatocellular carcinoma. Understanding these mechanisms plays an important role in the development of new diagnostic and therapeutic
 approaches to combat this dangerous form of liver cancer. Further research in this area will help expand our knowledge base and improve the
 HCC treatment.

Clinicopathological and Prognostic Significance of CCR5/CCL5 axis in Hepatocellular Carcinoma

Abstract Hepatocellular carcinoma (HCC) is one of the world’s most devastating malignancy which accounts for more than 90% liver cancer. The poor diagnosis of HCC lead’s scientists to search for novel treatment options to improve patient survival rates. There is accumulating evidence that chemokines and chemokine receptors (CCRs) contribute to tumor development and progression, as well as metastasis. Chemokine CCL5 (RANTES) has been reported to facilitate tumor progression and metastasis in various cancers, including liver cancer. However, the function of CCR5/CCL5 interaction in HCC proliferation and migration is poorly understood. Hence, the present study was undertaken to investigate the expression and role of the CCR5/CCL5 axis interface in the progression and invasiveness of HCC. In vitro study of liver cancer cell lines SNU387, PLC/PRF 5, and SK-HEP-1 showed higher expression of CCR5. Flow cytometry, RT-PCR, western blot, immunofluorescence techniques were used to quantify the expression of chemokine CCR5 and CCL5 in liver cancer cells. To determine the clinical significance of CCR5 expressed by HCC cell lines, a microarray of liver cancer tissues stained for CCR5 and CCL5 were analyzed. Our results show significantly (p< 0.001) higher expression of CCR5 and CCL5 in cancerous tissues compared to normal liver tissues. Furthermore, in order to delineate the role of CCR5/CCL5 interaction in HCC cell proliferation and migration, we pre-treated the HCC cell lines with the Maraviroc (CCR5 antagonist) in presence of CCL5. This data demonstrates both biological and clinical significance of CCR5 and CCL5 expression that may contribute to HCC metastasis, thus inhibition of its axis could be a promising avenue to treat liver cancer.

HEPATOCELLULAR CARCINOMA: DIAGNOSIS AND OPERATIVE MANAGEMENT.

ABSTRACT Introduction: Hepatocellular carcinoma is an aggressive malignant tumor with high lethality. Aim: To review diagnosis and management of hepatocellular carcinoma. Methods: Literature review using web databases Medline/PubMed. Results: Hepatocellular carcinoma is a common complication of hepatic cirrhosis. Chronic viral hepatitis B and C also constitute as risk factors for its development. In patients with cirrhosis, hepatocelular carcinoma usually rises upon malignant transformation of a dysplastic regenerative nodule. Differential diagnosis with other liver tumors is obtained through computed tomography scan with intravenous contrast. Magnetic resonance may be helpful in some instances. The only potentially curative treatment for hepatocellular carcinoma is tumor resection, which may be performed through partial liver resection or liver transplantation. Only 15% of all hepatocellular carcinomas are amenable to operative treatment. Patients with Child C liver cirrhosis are not amenable to partial liver resections. The only curative treatment for hepatocellular carcinomas in patients with Child C cirrhosis is liver transplantation. In most countries, only patients with hepatocellular carcinoma under Milan Criteria are considered candidates to a liver transplant. Conclusion: Hepatocellular carcinoma is potentially curable if discovered in its initial stages. Medical staff should be familiar with strategies for early diagnosis and treatment of hepatocellular carcinoma as a way to decrease mortality associated with this malignant neoplasm.

Open Access