Liver Hepatocellular Carcinoma Research Articles

A novel ubiquitination-related gene signature for overall survival prediction in patients with liver hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is a highly heterogeneous disease, necessitating the discovery of novel biomarkers to enhance individualized treatment approaches. Recent research has shown the significant involvement of ubiquitin-related genes (UbRGs) in the progression of LIHC. However, the prognostic value of UbRGs in LIHC has not been investigated. In this study, the mRNA expression profiles and clinical data were obtained from public databases of LIHC patients. The least absolute shrinkage and selection operator Cox regression model was employed to construct a multigene signature in the TCGA cohort. Our results showed that a twelve UbRGs signature was developed to categorize patients into two risk groups, with significant differences in expression between LIHC and normal tissues. Patients in the high-risk group exhibited significantly reduced overall survival (OS) and progression-free survival compared to those in the low-risk group. The risk score was identified as an independent predictor for OS in multivariate Cox regression analyses. Receiver operating characteristic curve analysis confirmed the predictive capacity of the signature. Functional analysis revealed enrichment of immune-related pathways and differences in immune status between the two risk groups. The risk score was correlated with 35 transcription factors and 26 eRNA enhancers, and positively associated with tumor mutation burden. Patients in the high-risk group demonstrated decreased sensitivity to targeted and chemotherapeutic drugs than those in the low-risk group. In conclusion, our study identified a twelve UbRGs signature that may serve as a prognostic predictor for LIHC patients and and provide valuable insights for cancer treatment.

Natural Compounds from Alhagi maurorum as Potential HCC and HepG2 Inhibitors: An Integrated Study using Pharmacophore Development, Molecular Docking, MD Simulation, and DFT Approaches.

The rise in the frequency of liver cancer all over the world makes it a prominent area of research in the discovery of new drugs or repurposing of existing drugs. This article describes the pharmacophore-based structure-activity relationship (3DQSAR) on the secondary metabolites of Alhagi maurorum to inhibit human liver cancer cell lines Hepatocellular carcinoma (HCC) and hepatoma G2 (HepG2) which represents the molecular level understanding for isolated phytochemicals of Alhagi maurorum. The definite features, such as hydrophobic regions, average shape, and active compounds' electrostatic patterns, were mapped to screen phytochemicals. The 3D-QSAR model generates pharmacophore-based descriptors and alignment of active compounds. Further, docking studies were performed on the active compounds to check out their binding affinity with the active site of the target proteins. It was further validated by applying molecular simulations, and the results were found to be accurate. The geometrical optimization and energy gap of the hit compound were calculated by the density functional theory (DFT). Then, ADMET was performed on this hit compound for drug-like features and toxicity. Out of 59 compounds, eight ligands were found active after the 3D-QSAR study. After that, molecular docking was performed on the active compounds F72, F52, F54, F29, F37, F38, F25, and F29, which were recognized as potential targets, and the docking results showed that compound F52 (also an FDA-approved drug) was the best hit. F52 was found to be the best hit against liver cancer cell lines HCC and HepG2. This study would be helpful for early drug discovery optimization and lead identification.

Lactulose use among patients with alcohol-related liver cirrhosis as a surrogate marker of hepatic encephalopathy: prevalence and association with mortality - a Danish nationwide cohort study

Background & aims: Hepatic encephalopathy (HE), one of the most serious prognostic factors for mortality in alcohol-related cirrhosis (ALD cirrhosis), is not recorded in Danish healthcare registries. However, treatment of HE with lactulose, the universal first-line treatment, can be identified through data on filled prescriptions. This study aimed to investigate if lactulose can be used as a surrogate marker of HE. Methods: We used Danish healthcare registries to establish a cohort of patients with ALD cirrhosis diagnosed in 2000–2018. Lactulose users were identified using data on filled prescriptions. We computed the prevalence and cumulative incidence of lactulose use, and then matched lactulose users with cohort members who were not using lactulose. This matched dataset was used to identify predictors of lactulose initiation, and to examine the association between lactulose use and all-cause mortality. Results: We included 23,089 patients, among whom we identified 4,789 first-time lactulose users. The prevalence of lactulose usage rose to 11% within the first 6 months after ALD diagnosis and reached 19% 5 years after inclusion. The 1-year cumulative incidence of lactulose use was 31%, and predictors of initiating lactulose use were history of severe liver disease (ascites, portal hypertension, spontaneous bacterial peritonitis or gastrointestinal bleeding) or hepatocellular carcinoma. Lactulose use was associated with higher mortality (adjusted hazard ratio 1.61 [95% confidence interval 1.53; 1.69]). Conclusions: Lactulose is used by 10–20% of patients with ALD cirrhosis, primarily those with severe cirrhosis, and lactulose users have a markedly higher mortality than nonusers. We conclude that lactulose use can be used to estimate the prevalence of HE and to reduce confounding from HE, but it should not be used as a surrogate for HE in studies with HE as an outcome.

Feasibility of indocyanine green fluorescence imaging to predict biliary complications in living donor liver transplantation: A pilot study.

Liver transplantation (LT) is now a critical, life-saving treatment for patients with liver cirrhosis or hepatocellular carcinoma. Despite its significant benefits, biliary complications (BCs) continue to be a major cause of postoperative morbidity. This study evaluates the fluorescence intensity (FI) of the common bile duct (CBD) utilizing near-infrared indocyanine green (ICG) imaging, and examines its association with the incidence of BCs within three months post-LT. This investigation analyzed data from nine living donor LT (LDLT) recipients who were administered 0.05 mg/kg of ICG prior to bile duct anastomosis. Real-time perfusion of the CBD was recorded for three minutes using an ICG camera, and FI was quantified using Image J (National Institutes of Health). Key parameters assessed included F max, F1/2 max, T1/2 max, and the slope (F max/T max) to evaluate the fluorescence response. BCs occurred in two out of nine patients. These two patients exhibited the longest T1/2 max values, which were linked with lower slope values, implicating a potential relationship between extended T1/2 max, reduced slope, and the occurrence of postoperative BCs. The study indicates that ICG fluorescence imaging may serve as an effective tool for assessing bile duct perfusion in LDLT patients. While the data suggest that an extended T1/2 max and lower slope may correlate with an increased risk of BCs, further validation through larger studies is required to confirm the predictive value of ICG fluorescence imaging in this setting.

Migrasome-related prognostic signature TSPAN4 correlates with immune infiltrates and metabolic disturbances in hepatocellular carcinoma.

We aim to comprehensively analyze and validate the prognostic efficacy of tetraspanin 4 (TSPAN4) and several other migrasome-related markers in hepatocellular carcinoma (HCC). The expression, diagnostic, and prognostic efficacy of five migrasome-related genes in HCC were analyzed using several databases. Five pairs of adjacent non-tumor tissues and HCC tissues were used to validate the expression. The prognostic efficacy of TSPAN4 was validated in a HCC cohort. TSPAN4 was knocked down in Huh-7 cells, EdU, and CCK-8, and wound healing assays were conducted to analyze its effects on cell proliferation and migration. In addition, transcriptomic sequencing was used to identify differentially expressed genes. Compared with those in normal tissues, four genes (TSPAN4, PIGK, NDST1, and CPQ) were elevated in liver hepatocellular carcinoma (LIHC), but not TSPAN7. Of these, only elevated TSPAN4 predicted unfavorable prognosis of HCC patients. The expression and prognostic efficacy of TSPAN4 were further confirmed in a HCC cohort (97 patients); and patients in the TSPAN4high group showed unfavorable overall survival (log-rank P = 0.0055). Functional analysis showed that TSPAN4 knockdown significantly suppressed cell migration, but not cell proliferation. Moreover, TSPAN4 knockdown induced disturbances of the metabolic pathways, mainly pentose and glucuronate interconversions. TPSAN4 is a promising prognostic and therapeutic target for HCC treatment and may be involved in the metabolic pathways that affect disease progression.

Lifestyle and Pharmacologic Approaches to Prevention of MASLD-related HCC.

Hepatocellular carcinoma (HCC) is a major concern for public health. Fatty liver disease, related to alcohol misuse or metabolic syndrome, has become the leading cause of chronic liver disease and HCC. The strong association between type 2 diabetes mellitus and HCC can be partly attributed to the development of metabolic dysfunction associated steatotic liver disease (MASLD). There is a strong interest in strategies that may mitigate HCC risk and reduce HCC incidence in this growing population of at-risk individuals. In this review, we describe the pathogenesis of HCC in patients with MASLD and discuss potential emerging pharmacological and lifestyle interventions for MASLD-related HCC. HCC risk has been observed to be lower with healthy lifestyle behaviors, such as healthy dietary patterns, e.g., high consumption of vegetables, whole grains, fish, and poultry, yogurt, and olive oil, and low consumption of red and processed meats and dietary sugar) and increased physical activity. Selecting an appropriate anti-diabetic therapy for individuals with liver disease and diabetes may also decrease the occurrence of HCC. Metformin, PPAR activators, sodium-glucose cotransporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RA), aspirin, and statins have all shown promise to reduce the risk of HCC, although guidelines do not recommend their use for the sole purpose of chemoprevention at this time given a dearth of data defining their risk-benefit ratio.

Investigating the Immunogenic Properties of a Mutagenized NS3/4A-Based HCV Genotype 3a DNA Vaccine.

Chronic hepatitis C virus (HCV) infection poses a major health risk worldwide, with patients susceptible to liver cirrhosis and hepatocellular carcinoma. This study focuses on the development of effective therapeutic strategies for HCV infection through the investigation of immunogenic properties of a DNA construct based on the NS3/4A gene of HCV genotype (g)3a. Gene expression of the mutagenized (mut) NS3/4A target genes was assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Additionally, bioinformatics tools were employed to evaluate the impact of the mut-NS3/4A-based DNA vaccine. Analysis revealed increased mut-NS3/4A mRNA levels and target protein abundance compared with the native sequence. Elevated mut-NS3/NS4A levels could result from increased RNA stability and proper protein folding. Physicochemical analyses of the protein demonstrated favorable attributes such as thermostability and solubility. Three-dimensional mut-NS3/4A protein modeling confirmed its high stability and agreement with known protein structures. Additionally, potential immunogenic regions of both T and B cell epitopes were discovered based on peptide binding to major histocompatibility complex molecules of Asian origin. Importantly, these epitopes exhibited nonallergenic and nontoxic characteristics. These findings highlight the potential of the NS3/4A-based DNA construct as a promising candidate for an HCVg3a vaccine tailored for the Asian population, providing valuable insights for future immunotherapeutic approaches.

DECODING THE RISK PROFILE OF NON-ALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: This is a systematic review and meta-analysis that aims to evaluate the prevalence of non-alcoholic fatty liver disease (NAFLD) and the risk factors such as type 2 diabetes mellitus (T2DM), hypertension, obesity, PCOS, and sleep apnea associated with it. NAFLD is one of the most prevalent diseases that affect approximately 40% of diabetic, hypertensive, dyslipidemic obese individuals. Its asymptomatic nature often leads to under diagnosis and progress to severe liver cirrhosis and hepatocellular carcinoma. Methods: A total of 1819 studies from database from 2019 to 2024 were identified, finally 10 studies were selected, the Statistical Package for the Social Sciences software was used for data analysis. Results: The analyses across different geographic regions with 620,3969 patients with NAFLD, T2DM prevalence came out to be 15% among males, whereas 22.2% in females. A prevalence of 52.55% was noted in the obese population and 26.74% in lean individuals, with PCOS 43%, metabolic syndrome 75.3%, and sleep apnea 40% and various risk factors were also identified. Conclusion: This review throws light on the nature of NAFLD, focusing on the need for increased awareness and screening among people at risk, strategies could help avert liver disease progression.

Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy.

To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival. Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC. To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model. Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features. Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis. Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.

The Human Pathology Atlas for deciphering the prognostic features of human cancers

Cancer is one of the leading causes of mortality worldwide, highlighting the urgent need for a deeper molecular understanding and the development of personalized treatments. The present study aims to establish a solid association between gene expression and patient survival outcomes to enhance the utility of the Human Pathology Atlas for cancer research. In this updated analysis, we examined the expression profiles of 6918 patients across 21 cancer types. We integrated data from 10 independent cancer cohorts, creating a cross-validated, reliable collection of prognostic genes. We applied systems biology approach to identify the association between gene expression profiles and patient survival outcomes. We further constructed prognostic regulatory networks for kidney renal clear cell carcinoma (KIRC) and liver hepatocellular carcinoma (LIHC), which elucidate the molecular underpinnings associated with patient survival in these cancers. We observed that gene expression during the transition from normal to tumorous tissue exhibited diverse shifting patterns in their original tissue locations. Significant correlations between gene expression and patient survival outcomes were identified in KIRC and LIHC among the major cancer types. Additionally, the prognostic regulatory network established for these two cancers showed the indicative capabilities of the Human Pathology Atlas and provides actionable insights for cancer research. The updated Human Pathology Atlas provides a significant foundation for precision oncology and the formulation of personalized treatment strategies. These findings deepen our understanding of cancer biology and have the potential to advance targeted therapeutic approaches in clinical practice. The Knut and Alice Wallenberg Foundation (72110), the China Scholarship Council (Grant No. 202006940003).

Morbid Obesity and Liver Transplant.

The progressive increase in the prevalence of morbid obesity (MO) in the general population is a pressing issue. This rise in MO has also been observed in patients with liver disease who are candidates for liver transplantation (LT). A retrospective study of a single-center series was conducted to analyze the impact of MO on morbidity, mortality, and patient survival after LT. Fifteen patients with a body mass index (BMI) of ≥ 40 kg/m2 (mean 40.4 ± 2.99 SD) were transplanted from 2004 to 2023. Thirteen were 13 men (87%) and 2 women (13%), with a mean age of 55 years (±9). The most common indication for LT was liver cirrhosis (93%: 6 alcohol related, 4 hepatitis C virus [HCV] related, and 3 from other causes), and only one case was due to hepatocellular carcinoma in a non-cirrhotic liver (7%). The median stay in the Intensive Care Unit was 5 days (range 2-52), with a median total hospital stay of 15 days (range 10-103). Five patients had a major complication each (≥ IIIa on the Clavien-Dindo scale): liver re-transplantation due to primary graft failure, reoperation due to hemoperitoneum, late superior mesenteric vein (SMV) thrombosis, acute renal failure that required hemodialysis, and surgical wound infection that required drainage. The only patient who required urgent re-transplantation (7%) had an adequate subsequent recovery without other complications. None of the patients underwent obesity surgery pre-, post-, or concurrently with the LT. Patient and graft survival after 5 years was 97%. In our experience, the outcomes of LT in patients with MO were satisfactory in terms of postoperative morbimortality, as well as in patient survival. Therefore, we do not support the notion of considering MO as a contraindication for LT.

Overview of chronic hepatitis B management.

Chronic hepatitis B remains a substantial global health challenge, impacting approximately 254 million people worldwide. A cure for this condition is yet to be discovered. Early identification and effective treatments coupled with vigilant monitoring can help alleviate associated morbidity and mortality due to potential complications such as liver cirrhosis and hepatocellular carcinoma.

Cost-effectiveness of monitoring and liver cancer surveillance among patients with inactive chronic hepatitis B.

Patients with chronic hepatitis B infection (CHB) have an increased risk for death from liver cirrhosis and hepatocellular carcinoma (HCC). In the United States, only an estimated 37% of adults with chronic hepatitis B diagnosis without cirrhosis receive monitoring with at least an annual alanine transaminase (ALT) and hepatitis B deoxyribonucleic acid (DNA), and an estimated 59% receive antiviral treatment when they develop active hepatitis or cirrhosis. A Markov model was used to calculate the costs, health impact and cost-effectiveness of increased monitoring of adults with HBeAg negative inactive or HBeAg positive immune tolerant CHB who have no cirrhosis or significant fibrosis and are not recommended by the current American Association for the Study of Liver Diseases (AASLD) clinical practice guidelines to receive antiviral treatment, and to assess whether the addition of HCC surveillance would be cost-effective. For every 100,000 adults with CHB who were initially not recommended for treatment, if the monitoring rate increased from the current 37% to 90% and treatment rate increased from 59% to 80%, 4,600 cases of cirrhosis, 2,450 cases of HCC and 4,700 HBV-related deaths would be averted with a gain of 45,000 QALYs and a savings of $180 million in lifetime health care costs. At a willingness to pay threshold of $100,000/QALY, the addition of HCC surveillance with the standard recommended biannual liver ultrasound and alfa fetoprotein levels is likely cost-effective if the HCC risk ≥ 0.55%/year. Regular monitoring of persons with inactive or immune tolerant CHB who are initially not recommended to receive antiviral treatment in the United States is cost-saving. The addition of HCC surveillance with biannual US and AFP would be cost-effective for individuals with HCC incidence ≥ 0.55%/year.

Current Role of Intraoperative Ultrasonography in Hepatectomy

Introduction: In the past decade, hepatectomy was associated with a high mortality rate due to insufficient surgical techniques, excessive intraoperative blood loss, errors in assessing liver function reserves, and various postoperative complications. Intraoperative ultrasonography (IOUS) offers real-time insights into the tumor’s quantity, size, location, and the vascular structure of the portal and hepatic veins. It assists the surgeon in identifying resection planes, contributing to improved surgical outcomes. This study aims to evaluate the current role of IOUS in hepatectomy. Methods: A descriptive cross-sectional study was conducted at Kathmandu Medical College Teaching Hospital, Nepal, from March 2022 to March 2024. Twenty-three patients undergoing various hepatectomy procedures, primarily for colorectal liver metastasis and hepatocellular carcinoma, were included. Intraoperative IOUS complemented preoperative triphasic CT scans and. data analysis was performed using SPSS Statistics version 16. Results: Out of 23 patients, 14 (60.8%) patients underwent segmentectomy, five (21.7%) right hemihepatectomy, two (8.6%) left hemihepatectomy, one (4.3%) left lateral sectionectomy and one (4.3%) right posterior sectionectomy. In seven patients (30.4%), IOUS provided additional information beyond what was seen on triphasic CT, resulting in a change in the surgical approach for four of them (17%). In all four patients, the change in surgical approach was proved to be correct based on the histological results. Notably, IOUS facilitated detailed anatomical mapping in 43% of cases, aiding in precise tumor localization relative to critical vascular structures. Conclusions: IOUS provides information on the hepatic anatomy in addition to supporting the final decision regarding which portion to resect. It is a safe technique that ensures favorable oncologic outcomes, especially in ultrasoundguided parenchyma-sparing surgeries for colorectal liver metastases.

Non-alcoholic Steatohepatitis Diagnosis and Treatment – Current Concepts

NAFLD (Non-alcoholic fatty liver disease) is a condition of high importance due to its increased prevalence, estimated at 24% of the global population, and its potential progression to advanced liver disease, cirrhosis, and hepatocellular carcinoma. One-quarter of NAFLD patients have NASH (non-alcoholic steatohepatitis), which is histologically described as liver steatosis, inflammation, fibrosis, hepatocyte injury, and death. Metabolic disruptions, such as obesity, diabetes, and dyslipidemia, are considered to have a great impact on the development of NASH. Patients may have NAFLD for a long time before progressing into NASH, which highlights the necessity of periodic imaging and biochemical evaluation of the liver, and also presents an optimal window of therapeutic intervention. The challenge in developing treatment for NASH stems from the slow progression of the disease and the reliance on sequential biopsies as the diagnostic and staging tools. Several non-invasive tests have been developed as potential future alternatives to the current invasive gold standard. This review aims to assess the current available methods of diagnosis and treatment targeting inflammation.

Hepatocellular carcinoma: Revising the surgical approach in light of the concept of multiparametric therapeutic hierarchy.

The clinical management of hepatocellular carcinoma (HCC) is strongly influenced by several prognostic factors, mainly tumor stage, patient's health, liver function and specific characteristics of each intervention. The interplay between these factors should be carefully evaluated by a multidisciplinary tumor board. To support this, the novel "multiparametric therapeutic hierarchy" (MTH) concept has been recently proposed. This review will present the main features of available surgical treatments for HCC (liver transplantation, liver resection, ablation). Strengths and weaknesses are reported in the light of clinical decision making and of treatment allocation, with a special focus on the collocation of each treatment in the MTH framework and on how MTH may be useful in supporting clinical decision. Sequential treatments and their role to allow further surgical treatments will also be analyzed.

Roles of Cellular Neighborhoods in Hepatocellular Carcinoma Pathogenesis.

The development of hepatocellular carcinoma (HCC) involves an intricate interplay among various cell types within the liver. Unraveling the orchestration of these cells, particularly in the context of various etiologies, may hold the key to deciphering the underlying mechanisms of this complex disease. The advancement of single-cell and spatial technologies has revolutionized our ability to determine cellular neighborhoods and understand their crucial roles in disease pathogenesis. In this review, we highlight the current research landscape on cellular neighborhoods in chronic liver disease and HCC, as well as the emerging computational approaches applicable to delineate disease-associated cellular neighborhoods, which may offer insights into the molecular mechanisms underlying HCC pathogenesis and pave the way for effective disease interventions.

Advancements in Antiviral Therapeutics: A Comprehensive Review of Hepatitis C Virus and Novel Flavone Leads

This review explores the fundamental characteristics and implications of viruses, focusing on their classification, structure, and the specific case of Hepatitis C Virus (HCV). Viruses, nonliving biological entities reliant on host cells for replication, have been historically pivotal in understanding infectious diseases. The classification of viruses has evolved significantly, leading to a hierarchical system that categorizes them by order, family, genus, and species based on genomic characteristics and structural features. HCV, a member of the Flaviviridae family, presents a significant global health concern, affecting over 150 million people and causing approximately 500,000 deaths annually. The virus is characterized by its enveloped structure and single-stranded RNA genome, which encodes a polyprotein that is cleaved into functional proteins essential for viral replication and assembly. The epidemiology of HCV reveals regional prevalence variations, with higher rates observed in developing countries. Notably, the virus exhibits considerable genetic diversity, categorized into seven genotypes, each demonstrating different responses to treatment. The natural history of HCV infection is complex, often remaining asymptomatic for extended periods, which complicates diagnosis and treatment initiation. Chronic infections can lead to severe complications, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. Understanding the mechanisms of HCV entry, replication, and immune evasion is crucial for developing effective antiviral therapies and preventive measures. This review aims to provide a comprehensive overview of the current knowledge surrounding HCV, highlighting the need for ongoing research to better understand its biology and to improve therapeutic strategies against this pervasive virus.

Pan-cancer analysis of the potential of PEA3 subfamily genes as tumor markers

Polyomavirus enhancer activator 3 (PEA3), an ETS transcription factor, has been documented to regulate the development and metastasis of human cancers. Nonetheless, a thorough analysis examining the relationship between the PEA3 subfamily members and tumour development, prognosis, and the tumour microenvironment (TME) across various cancer types has not yet been conducted. The expression profiles and prognostic significance of the PEA3 subfamily were evaluated using data from the GEO, TCGA, and PrognoScan databases, in conjunction with COX regression analyses and the Kaplan–Meier Plotter. Furthermore, the relationships between PEA3 subfamily expression, stemness scores, tumor microenvironments, immune subtypes, and drug susceptibility across multiple cancer types were explored. We found that ETV1, ETV4 and ETV5 are highly expressed in cancer, and their biological functions are synergistic. In the prognostic analysis of the Cancer Genome Atlas, the PEA3 subfamily genes were found to be associated with the prognosis of multiple cancers such as Lung adenocarcinoma (LUAD), Liver hepatocellular carcinoma (LIHC), etc., and marked a worse prognosis at different endpoints. In addition, it was significantly correlated with the stromal and immune scores of pan-cancer, and also significantly associated with the RNA stemness score and DNA stemness score of pan-cancer. Expression levels of the PEA3 subfamily genes correlate with immune subtypes of LIHC, LUAD, and Lung squamous cell carcinoma. We also found a variety of drugs with positive and negative associations of ETV1, ETV4 and ETV5. These findings elucidate the role of the PEA3 subfamily gene as a biomarker for carcinogenesis and cancer progression, offering valuable insights for future research into the PEA3 subfamily gene as a potential therapeutic target across various cancer types.

CYB561 a potential prognostic biomarker for liver hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is a malignancy characterized by a high rate of recurrence, metastasis, and poor prognosis. Cytochrome b561 (CYB561) has been previously reported to be associated with tumor progression, but it has not been revealed in LIHC. The aim of this study was to investigate the prognostic value and potential function of CYB561 in LICH. The expression level, clinical correlation, prognosis, and biological function of CYB561 in LIHC were analyzed using The Cancer Genome Atlas（TCGA), Gene Expression Omnibus (GEO), TIMER2, Kaplan–Meier Plotter, and GEPIA2 databases. The expression of CYB561 in LIHC tissue samples was analyzed by immunohistochemical staining. The effect of CYB561 on the proliferation and migration of LIHC cells was investigated by using CYB561 knockdown in vitro. GSE149614 dataset was used to analyze the expression distribution of CYB561 in LIHC on a single-cell dimension. This study showed that CYB561 mRNA and protein were highly expressed in LIHC. High expression of CYB561 suggests poor prognosis in LICH patients and is an independent risk factor for LIHC. Wound-healing experiment, transwell experiment, and clonal formation experiment confirmed that CYB561 knockdown could inhibit the proliferation and migration of LIHC cells. Functional enrichment analysis showed that CYB561 was related to biological processes such as cell adhesion and immune response. KEGG enrichment analysis showed that CYB561 interacts with tumor-related signaling pathways. Single-cell analysis showed that CYB561 was mainly expressed in hepatocytes. Cells with high CYB561 expression had a higher degree of malignancy. Our study found that abnormal expression of CYB561 in LIHC suggested poor prognosis of LIHC and was related to tumor migration and proliferation. CYB561 is a potential prognostic predictor or therapeutic biomarker.