Liver Hepatocellular Carcinoma Research Articles

FGA influences invasion and metastasis of hepatocellular carcinoma through the PI3K/AKT pathway.

Fibrinogen is an important plasma protein composed of three polypeptide chains, fibrinogen alpha (FGA), beta, and gamma. Apart from being an inflammation regulator, fibrinogen also plays a role in tumor progression. Liver cancer usually has a poor prognosis, with chronic hepatitis being the main cause of liver cirrhosis and hepatocellular carcinoma (HCC). FGA serves as a serological marker for chronic hepatitis, but its relationship with liver cancer remains unclear. Through bioinformatics analysis and agarose gel electrophoresis, we found that FGA was downregulated in HCC and correlated with tumor stage and grade. By constructing both FGA gene knockout and overexpression cell models, we demonstrated that overexpressing FGA inhibited migration and invasion of liver cancer cells through Transwell migration/invasion and wound healing assays. Western blotting experiments showed that FGA overexpression increased the expression of the epithelial-mesenchymal transition marker protein E-cadherin while decreasing N-cadherin and slug protein expression. In addition, FGA knockout activated the PI3K/AKT pathway. In a mouse model of metastatic tumors, overexpression of FGA restricted the spread of tumor cells. In conclusion, FGA exhibits an inhibitory effect on tumor metastasis, providing new insights for the treatment of advanced HCC metastatic tumors.

Comprehensive analysis of PSMG3 in pan-cancer and validation of its role in hepatocellular carcinoma.

Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC). We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines. PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells. Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC.

Membranoproliferative glomerulonephritis in a child with congenital portosystemic shunt.

Congenital portosystemic shunts (CPSS) are rare congenital vascular anomalies characterized by abnormal connections between the portal vein and systemic circulation, bypassing the liver. They can lead to complications such as recurrent encephalopathy, liver nodules, portopulmonary hypertension, and neurocognitive issues due to hyperammonemia and rarely kidney involvement. Hepatic hemodynamic changes can lead to liver nodules and hepatocellular carcinoma, particularly in extrahepatic shunts. We describe here an 11-year-old girl with type 1 intrahepatic portosystemic shunt with focal nodular hyperplasia in the liver, presenting with nephrotic syndrome that was diagnosed as membranoproliferative glomerulonephritis on kidney biopsy and that responded partially to therapy with immunosuppressants.

An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects.MethodsThe GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice.ResultsThrough machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive.ConclusionsData from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People’s Hospital in 2021 (ChiCTR1900024415).

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4weeks for new-onset LC and liver-related events. Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Evaluation of Serum Kallistatin in Patients with Hepatocellular Carcinoma

Abstract Background Liver cirrhosis is the most frequent long-term consequence of all chronic liver diseases. Cirrhosis is often asymptomatic and unsuspected until complications. The annual incidence rates of liver cirrhosis and hepatocellular carcinoma is related with chronic hepatitis B or C all over the world. The majority of patients with liver cirrhosis or hepatocellular carcinoma die from complications, which happened relatively early in the course of the disease. Thus, the early diagnosis of liver diseases is the only solution for this great problem. Aim of the Work In the current study we aimed to evaluate serum kallistatin in Egyptian patients with hepatitis C virus related liver cirrhosis and hepatocellular carcinoma. Patients and Methods This case control study enrolled 90 Egyptian subjects aged ≥ 18 years old at Ain shams university hospitals, participants were classified into 3 groups as follow: Group 1: 30 patients with hepatocellular carcinoma (patients have been diagnosed with triphasic CT). Group 2: 30 patients with hepatitis C virus related liver cirrhosis (patients diagnosed according to clinical, laboratory and radiological findings. Group 3: 30 healthy subjects serving as a control group. Results This study found that patients with liver cirrhosis and HCC have lower levels of serum Kallistatin compared to a control group. In the HCC group, patients with more severe liver disease (Child class C) had lower Kallistatin levels than those with less severe disease (Child class A and B). Kallistatin was negatively correlated with certain markers of liver disease and inflammation in both groups, and positively correlated with hemoglobin and albumin. The study also tested the diagnostic accuracy of Kallistatin for detecting liver cirrhosis and HCC, and found that it had 66.5% accuracy for cirrhosis and 98% accuracy for HCC at specific cutoff points. Conclusion Serum Kallistatin has a potential rule as a new biomarker for the diagnosis and evaluation of liver cirrhosis and HCC. The present study was limited by the small sample size. Also, all participants were from the Egyptian population with liver disease induced by HCV- infection with no information if our findings would be valid for other population with different etiologies. Thus, further investigation should be carried out in order to validate these findings

Safety Implications of Modulating Nuclear Receptors: A Comprehensive Analysis from Non-Clinical and Clinical Perspectives.

The unintended modulation of nuclear receptor (NR) activity by drugs can lead to toxicities amongst the endocrine, gastrointestinal, hepatic cardiovascular, and central nervous systems. While secondary pharmacology screening assays include NRs, safety risks due to unintended interactions of small molecule drugs with NRs remain poorly understood. To identify potential nonclinical and clinical safety effects resulting from functional interactions with 44 of the 48 human-expressed NRs, we conducted a systematic narrative review of the scientific literature, tissue expression data, and used curated databases (OFF-X™) (Off-X, Clarivate) to organize reported toxicities linked to the functional modulation of NRs in a tabular and machine-readable format. The top five NRs associated with the highest number of safety alerts from peer-reviewed journals, regulatory agency communications, congresses/conferences, clinical trial registries, and company communications were the Glucocorticoid Receptor (GR, 18,328), Androgen Receptor (AR, 18,219), Estrogen Receptor (ER, 12,028), Retinoic acid receptors (RAR, 10,450), and Pregnane X receptor (PXR, 8044). Toxicities associated with NR modulation include hepatotoxicity, cardiotoxicity, endocrine disruption, carcinogenicity, metabolic disorders, and neurotoxicity. These toxicities often arise from the dysregulation of receptors like Peroxisome proliferator-activated receptors (PPARα, PPARγ), the ER, PXR, AR, and GR. This dysregulation leads to various health issues, including liver enlargement, hepatocellular carcinoma, heart-related problems, hormonal imbalances, tumor growth, metabolic syndromes, and brain function impairment. Gene expression analysis using heatmaps for human and rat tissues complemented the functional modulation of NRs associated with the reported toxicities. Interestingly, certain NRs showed ubiquitous expression in tissues not previously linked to toxicities, suggesting the potential utilization of organ-specific NR interactions for therapeutic purposes.

The Association of Serum Ferritin with Disease Severity in Non-alcoholic Fatty Liver Disease

Abstract Background NONALCOHOLIC FATTY LIVER DISEASE is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. Aim of the Work The aim of this study is to evaluate the association of serum ferritin with non- alcoholic fatty liver disease. Patients and Methods The study was cross sectional study which conducted at Ain Shams University Hospital. This study was conducted on 80 patients both sexes, with age (18years old - 60 years), duration of study will be 6 months. All study patients approved to participate in this study. Patients were divided in to 2 groups as following: Results Our study reveals that patients with non alcoholic steatohepatitis (NASH) have significantly higher median serum ferritin levels, compared to those with non alcohoholic fatty liver disease (NAFLD). Also ROC curve shows that the best cutoff point of serum ferritin to differentiate between normal lipid profile group and elevated lipid profile group was found &amp;gt; 80 with sensitivity of 82.5%, specificity of 60.0% and AUC of 69.5% while the best cutoff point of fatty liver index to differentiate between normal lipid profile group and elevated lipid profile group was found &amp;gt; 89 with sensitivity of 67.5%, specificity of 80.0% and AUC of 76.8%. Conclusion Elevated serum ferritin may reflect increased disease severity in NAFLD either because of increased ongoing hepatic or systemic inflammation or increased body iron stores or a combination of these factors. Our study also reveals that patients with non alcoholic steatohepatitis (NASH) have significantly higher median serum ferritin levels, compared to those with non alcohoholic fatty liver disease (NAFLD).

X-ray Repair Cross Complementing 1 (XRCC1) Gene Polymorphism in Hepatocellular Carcinoma (HCC)

Abstract Background Several risk factors for hepatocellular carcinoma (HCC) have been identified, including chronic infection of hepatitis B virus (HBV) and hepatitis C virus (HCV). Nevertheless, only a fraction of infected patients develops HCC during their lifetime suggesting that genetic factors might modulate HCC development. The human X-ray repair cross- complementing protein 1 (XRCC1) gene encodes for one of the major repair factors involved in base excision repair (BER), which is reported to be associated with the risk of several cancers. A few studies have explored the association between risk of hepatocellular carcinoma (HCC) and single-nucleotide polymorphisms (SNPs) in different DNA repair genes. Aim of the Work to investigate the possible association between XRCC1-G28152A (rs25487) single nucleotide polymorphism (SNP) and hepatocellular carcinoma (HCC) in chronic hepatitis C patients. Patients and Methods The study included 35 patients who had HCC and 15 patients who had liver cirrhosis. XRCC1 gene polymorphism was done to all participants by RT-PCR After collection of relevant clinical data and basic laboratory tests. Results A statistically higher frequency of XRCC1 (GG, GA) genotypes and increased (G) allele frequency in patients with HCC was found in comparison to cirrhotic HCV patients as well as control group but Our results revealed that the genotypic and allelic frequencies of XRCC1 gene polymorphism rs25487 didn’t show statistically significant difference between HCC patients group and liver cirrhosis control group. Conclusion The present study had demonstrated that there was no significant association between XRCC1 gene polymorphism (rs25487) and HCC in the sample of Egyptian population included in our study. Also, non-significant differences among the XRCC1 genotypes and alleles were found regarding age, sex, BMI and laboratory data including CBC, AFP, coagulation profile (PT, INR), liver function test ( total protein, albumin, AST, total bilirubin and direct bilirubin), BCLC and Milan criteria. While a statistically significant difference was observed as regards PTT and ALT between genotypes.

71 Stereotactic Ablative Radiotherapy Is a Safe and Feasible Treatment Option for Patients with Hepatocellular Carcinoma

Abstract Aim Stereotactic ablative body radiotherapy (SABR) is a highly focused radiation treatment that delivers an intense dose of radiation to a tumour whilst limiting exposure of surrounding tissues. SABR has been associated with improvement in survival and good rates of local control in non-surgical candidates with hepatocellular carcinoma (HCC). The aim of this study was to evaluate the outcomes of HCC patients treated with SABR after its introduction in a tertiary referral hepatobiliary centre. Method A total of 32 patients (median age 73 years {47 to 85}, 78% male) who received SABR for HCC liver lesions between July 2020 and August 2022 were retrospectively analysed. Patient, treatment, and follow-up details were obtained from online patient records and imaging. Results Overall Survival rate was 78% at a median follow-up of 12 months (range 4 to 30). Local control was achieved in 72%, while progression occurred in 31%. Median time to progression was 6 months (range 3 to 31). The rate of progression-free survival at 12 months was 62.5%. Only 31% reported toxicities. No patients in the study group experienced any Grade ³ 3 toxicities. Conclusions Our experience following the introduction of SABR for patients with HCC is that SABR is a viable, well-tolerated and effective treatment option in this patient group. Further research is warranted to examine the clinical benefits of combination treatment with SABR and other treatment modalities to maximise disease control in patients with both early and advanced HCC.

TCBIR/CD320: a potential therapeutic target upregulated in endothelial cells and associated with immune cell infiltration in liver hepatocellular carcinoma

CD320, which is a transmembrane protein responsible for facilitating the absorption of vitamin B12, plays a key role in this process. However, the relationships between CD320 and immune cell infiltration levels remain unclear, with limited studies investigating the diagnostic and prognostic significance of CD320 in hepatocellular carcinoma. We used various databases, including the TIMER, GEPIA, UALCAN and TCGA databases to investigate the expression levels of CD320 in hepatocellular carcinoma. Subsequently, we analyzed the prognosis of hepatocellular carcinoma patients with different expression levels of CD320. Furthermore, we also performed Western blot, immunohistochemistry, and immunofluorescence analyses to validate the results of the database analysis. Finally, the functions of CD320 in hepatocellular carcinoma were also confirmed via relevant cell experiments and angiogenesis assays. We found that CD320 expression was significantly upregulated in tumor vascular endothelial cells. Moreover, the knockdown of CD320 led to a reduction in angiogenesis in endothelial cells. Increased expression of CD320 was also correlated with a poor prognosis in patients with hepatocellular carcinoma, which suggested that CD320 may be a potential prognostic marker. Finally, TIMER analysis demonstrated that the infiltration of six immune cell types was significantly associated with high expression levels of CD320 in hepatocellular carcinoma. Herein, we demonstrated that CD320 may play an important role in angiogenesis in hepatocellular carcinoma. These findings suggested that CD320 may be a potential clinical prognostic marker and immunotherapy target for hepatocellular carcinoma.

Targeting AFP-RARβ complex formation: a potential strategy for treating AFP-positive hepatocellular carcinoma.

Alpha-fetoprotein (AFP) is a glycoprotein primarily expressed during embryogenesis, with declining levels postnatally. Elevated AFP levels correlate with pathological conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent investigations underscore AFP's intracellular role in HCC progression, wherein it forms complexes with proteins like Phosphatase and tensin homolog (PTEN), Caspase 3 (CASP3), and Retinoic acid receptors and Retinoid X receptors (RAR/RXR). RAR and RXR regulate gene expression linked to cell death and tumorigenesis in normal physiology. AFP impedes RAR/RXR dimerization, nuclear translocation, and function, promoting gene expression favoring cancer progression in HCC that provoked us to target AFP as a drug candidate. Despite extensive studies, inhibitors targeting AFP to disrupt complex formation and activities remain scarce. In this study, employing protein-protein docking, amino acid residues involved in AFP-RARβ interaction were identified, guiding the definition of AFP's active site for potential inhibitor screening. Currently, kinase inhibitors play a significant role in cancer treatment and, the present study explores the potential of repurposing FDA-approved protein kinase inhibitors to target AFP. Molecular docking with kinase inhibitors revealed Lapatinib as a candidate drug of the AFP-RARβ complex. Molecular dynamics simulations and binding energy calculations, employing Mechanic/Poisson-Boltzmann Surface Area (MM-PBSA), confirmed Lapatinib's stability with AFP. The study suggests Lapatinib's potential in disrupting the AFP-RARβ complex, providing a promising avenue for treating molecularly stratified AFP-positive HCC or its early stages.

Gene signature developed based on programmed cell death to predict the therapeutic response and prognosis for liver hepatocellular carcinoma

BackgroundThe prognosis and therapeutic response of patients with liver hepatocellular carcinoma (LIHC) can be predicted based on programmed cell death (PCD) as PCD plays a crucial role during tumor progression. We developed a PCD-related gene signature to evaluate the therapeutic response and prognosis for patients with LIHC. MethodsMolecular subtypes of LIHC were classified using ConsensusClusterPlus according to the gene biomarkers related to PCD. To predict the prognosis of high- and low-risk LIHC patients, a risk model was established by LASSO regression analysis based on the prognostic genes. Functional enrichment analysis was conducted using clusterProfiler package, and relative abundance of immune cells was quantified applying CIBERSORT package. Finally, to determine drug sensitivity, oncoPredict package was employed. ResultsPCD was correlated with the clinicopathologic features of LIHC. Then, we defined four molecular subtypes (C1–C4) of LIHC using PCD-related prognostic genes. Specifically, subtype C1 had the worst prognosis with enriched T cells regulatory (Tregs) and Macrophage_M0 and higher expression of T cell exhaustion markers, meanwhile, C1 also had a relatively higher TIDE score and metastasis potential. A risk model was established using 5 prognostic genes. High-risk patients tended to have higher expression of T cell exhaustion markers and TIDE score and unfavorable outcomes, and they were more sensitive to small molecule drug 5.Fluorouracil. ConclusionA PCD-related gene signature was developed and verified to be able to accurately predict the prognosis and drug sensitivity of LIHC patients.

Strategies to enhance the response of liver cancer to pharmacological treatments.

In contrast to other types of cancers, there is no available efficient pharmacological treatment to improve the outcomes of patients suffering from major primary liver cancers, i.e., hepatocellular carcinoma and cholangiocarcinoma. This dismal situation is partly due to the existence in these tumors of many different and synergistic mechanisms of resistance, accounting for the lack of response of these patients, not only to classical chemotherapy but also to more modern pharmacological agents based on the inhibition of tyrosine kinase receptors (TKIs) and the stimulation of the immune response against the tumor using immune checkpoint inhibitors (ICIs). This review summarizes the efforts to develop strategies to overcome this severe limitation, including searching for novel drugs derived from synthetic, semisynthetic, or natural products with vectorial properties against therapeutic targets to increase drug uptake or reduce drug export from cancer cells. Besides, immunotherapy is a promising line of research that is already starting to be implemented in clinical practice. Although less successful than in other cancers, the foreseen future for this strategy in treating liver cancers is considerable. Similarly, the pharmacological inhibition of epigenetic targets is highly promising. Many novel "epidrugs," able to act on "writer," "reader," and "eraser" epigenetic players, are currently being evaluated in preclinical and clinical studies. Finally, gene therapy is a broad field of research in the fight against liver cancer chemoresistance, based on the impressive advances recently achieved in gene manipulation. In sum, although the present is still dismal, there is reason for hope in the non-too-distant future.

Correlation analysis of gamma-glutamyl transferase to lymphocyte ratio and patients with acute aortic syndrome in China: a propensity score-matched analysis.

Acute aortic syndrome (AAS) is a life-threatening condition in which there is a fracture in the integrity of the aortic wall. gamma-glutamyl transferase to lymphocyte ratio (GLR) is recognized as a risk factor for liver cirrhosis, fibrosis, and hepatocellular carcinoma. However, there are no clinical reports of GLR and AAS. We attempted to determine whether GLR level is associated with AAS in patients from the Chaoshan region of southern China. A total of 2,384 patients were recruited in this study and were divided into AAS and no-AAS groups according to the results of CT angiography of the thoracoabdominal aorta. Univariate and multivariate logistic regression was performed to identify risk factors for the occurrence of AAS. ROC was applied to assess the value of D-Dimer, GLR alone, or in combination for the diagnosis of AAS. And a 1:1 propensity score-matched analysis was performed. Multivariate logistics regression analysis indicated that male, age, hypertension, diabetes, creatinine, D-dimer, and GLR were independent risk factors of AAS patients in the before propensity score-matching cohort. After propensity score-matching, it showed that D-dimer, GLR [OR 3.558(1.891, 6.697); p < 0.001] were independent risk factors of AAS patients. Before propensity score-matching, the area under the curve (AUC) was 0.822 of GLR and 0.767 of D-dimer. When both clinical backgrounds were adjusted, the AUC was 0.773 of GLR and 0.631 of D-dimer. GLR showed high specificity (80.5% and 77.1%), and D-dimer showed high sensitivity (84.7% and 73.6%) in the before and after propensity score-matching cohort. GLR and D-dimer were independent risk factors of acute aortic syndrome. D-dimer in combination with GLR is more valuable than a single indicator for diagnosing acute aortic syndrome.

CDK1 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Pan-Cancer, Especially in Gastrointestinal Tumors.

Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between CDK1 expression and immune cell infiltration. CDK1 expression and its correlation with prognosis in pan-cancer were analyzed using online databases. Immune infiltration was assessed by ESTIMATE and CIBERSORT algorithms. We then evaluated the relationship between CDK1 expression and tumor mutational burden (TMB), microsatellite instability (MSI), or tumor-infiltrating immune cells. In addition, we performed the co-expression analysis of immune-related genes and GO analysis with CDK1 expression in pan-cancer. Finally, we compared the CDK1 expression profile with the immune-related genes in 30 pairs of clinical gastrointestinal tumor samples. Our analysis demonstrated overexpression of CDK1 in most tumor tissues, especially in gastrointestinal tumors. The high expression of CDK1 was associated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), and sarcoma (SARC). Besides, CDK1 expression was significantly associated with TMB in 22 cancer types and MSI in 8 cancer types as well as greater frequencies of MSI-high (MSI-H) status and high tumor mutational burden (TMB-H) in uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), sarcoma (SARC), rectum adenocarcinoma (READ), mesothelioma (MESO), head and neck squamous cell carcinoma (HNSC), and colon adenocarcinoma (COAD). In addition, CDK1 expression correlated with immune cell infiltrating levels, such as M0, M1, or M2 macrophages, memory CD4 T cells, T follicular helper cells, and naive B cells. Our data showed that CDK1 was remarkably correlated with 47 immune-related and immune checkpoint genes in many cancer types. Furthermore, CDK1 was up-regulated in gastrointestinal tumor samples, especially in gastric cancer and intestinal cancer. CDK1 was positively correlated with IDO1 in gastric cancer and PD-1 in intestinal cancer. Taken together, our data demonstrated the roles of CDK1 in oncogenesis and metastasis in pan-cancer. Thus, CDK1 is a potential prognostic biomarker and a target for tumor immunotherapy.

A Bioinformatics-Based Approach to Discover Novel Biomarkers in Hepatocellular Carcinoma

Background: Liver hepatocellular carcinoma (LIHC) is a common cancer with a poor prognosis and high recurrence rate. We aimed to identify potential biomarkers for LIHC by investigating the involvement of hub genes, microRNAs (miRNAs), transcription factors (TFs), and protein kinases (PKs) in its occurrence. Methods: we conducted a bioinformatics analysis using microarray datasets, the TCGA-LIHC dataset, and text mining to identify differentially expressed genes (DEGs) associated with LIHC. They then performed functional enrichment analysis and gene-disease association analysis. The protein-protein interaction network of the genes was established, and hub genes were identified. The expression levels and survival analysis of these hub genes were evaluated, and their association with miRNAs, TFs, and PKs was assessed. Results: The analysis identified 122 common genes involved in LIHC pathogenesis. Ten hub genes were filtered out, including CDK1, CCNB1, CCNB2, CCNA2, ASPM, NCAPG, BIRC5, RRM2, KIF20A, and CENPF. The expression level of all hub genes was confirmed, and high expression levels of all hub genes were correlated with poor overall survival of LIHC patients. Conclusion: Identifying potential biomarkers for LIHC can aid in the design of targeted treatments and improve the survival of LIHC patients. The findings of this study provide a basis for further research in the field of LIHC and contribute to the understanding of its molecular pathogenesis.

Exploring the Roles of Key Mediators IKBKE and HSPA1A in Alzheimer's Disease and Hepatocellular Carcinoma through Bioinformatics Analysis.

Recent studies have hinted at a potential link between Alzheimer's Disease (AD) and cancer. Thus, our study focused on finding genes common to AD and Liver Hepatocellular Carcinoma (LIHC), assessing their promise as diagnostic indicators and guiding future treatment approaches for both conditions. Our research utilized a broad methodology, including differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), gene enrichment analysis, Receiver Operating Characteristic (ROC) curves, and Kaplan-Meier plots, supplemented with immunohistochemistry data from the Human Protein Atlas (HPA) and machine learning techniques, to identify critical genes and significant pathways shared between AD and LIHC. Through differential gene expression analysis, WGCNA, and machine learning methods, we identified nine key genes associated with AD, which served as entry points for LIHC analysis. Subsequent analyses revealed IKBKE and HSPA1A as shared pivotal genes in patients with AD and LIHC, suggesting these genes as potential targets for intervention in both conditions. Our study indicates that IKBKE and HSPA1A could influence the onset and progression of AD and LIHC by modulating the infiltration levels of immune cells. This lays a foundation for future research into targeted therapies based on their shared mechanisms.

Comorbid background on the waiting list for liver transplantation. Clinical case of liver cirrhosis as a result of chronic viral hepatitis B with a delta agent in combination with cardiac arrhythmia

Hepatitis D virus is a dependent virus that depends on hepatitis B virus for replication and transmission. Chronic hepatitis D virus (HDV) is a severe form of viral hepatitis that can lead to end-stage liver disease and hepatocellular carcinoma. Liver transplantation (LT) is the only treatment option for patients with end-stage liver disease, hepatocellular carcinoma, or fulminant hepatitis caused by HDV coinfection. Also, the presence of a comorbid background is associated with a higher rate of complications, longer hospitalization and worse survival both before and after LT. We present a case of liver cirrhosis as a result of HBV+HDV co-infection in combination with arrhythmia in a patient on the waiting list for LT in the Rostov region.

Understanding the heterogeneity in liver hepatocellular carcinoma with a special focus on malignant cell through single-cell analysis

IntroductionHepatocellular carcinoma (HCC) is the most common form of liver cancer globally and remains a major cause of cancer-related deaths. HCC exhibits significant intra-tumoral and interpatient heterogeneity, impacting treatment efficacy and patient prognosis.MethodsWe acquired transcriptome data from the TCGA and ICGC databases, as well as liver cancer chip data from the GEO database, and processed the data for subsequent analysis. We also obtained single cell data from the GEO database and performed data analysis using the Seurat package. To further investigate epithelial cell subgroups and their copy number variations, we used the Seurat workflow for subgroup classification and the InferCNV software for CNV analysis, utilizing endothelial cells as a reference. Pseudo-time analysis and transcription factor analysis of epithelial cells were performed using the monocle2 and SCENIC software, respectively. To assess intercellular communication, we employed the CellChat package to identify potential ligand-receptor interactions. We also analyzed gene expression differences and conducted enrichment analysis using the limma and clusterProfiler packages. Additionally, we established tumor-related risk characteristics using Cox analysis and Lasso regression, and predicted immunotherapy response using various datasets.ResultsThe samples were classified into 23 clusters, with malignant epithelial cells being the majority. Trajectory analysis revealed the differentiation states of the malignant epithelial cells, with cluster 1 being in the terminal state. Functional analysis revealed higher aggressiveness and epithelial-mesenchymal transition (EMT) scores in cluster 1, indicating a higher propensity for metastasis. RBP4+ tumor cells were highly enriched with hypoxia process and intensive cell-to-cell communication. A prognostic model was established, and immune infiltration analysis showed increased infiltration in the high-risk group. TP53 demonstrated significant differences in mutation rate between the two risk groups. Validation analysis confirmed the up-regulation of model genes, including AKR1B10, ARL6IP4, ATP6V0B, and BSG in tumor tissues.ConclusionA prognostic model was established based on HCC malignant cell associated gene signature, displaying decent prognosis guiding effectiveness in the multiple cohorts. The study provided comprehensive insights into the heterogeneity and potential therapeutic targets of LIHC.