Biomarker For Hepatocellular Carcinoma Research Articles

Bioinformatics combined with network pharmacology and experimental validation to identify key biomarkers of hepatocellular carcinoma and corresponding compounds in Radix Astragali and Pueraria Mirifica.

The occurrence and death rates of primary hepatocellular carcinoma (HCC) are increasing, and there remains a shortage of effective oral medications with minimal side effects. We aim to identify potential biomarkers and compounds from Radix Astragali (RA) and Pueraria Mirifica (PM) to treat liver cancer and improve prognosis. Differentially expressed genes (DEGs) associated with HCC were identified by bioinformatics analysis of three datasets, GSE112791, GSE101685, and GSE45114. Using public databases to predict the bioactive components and possible targets of RA and PM. Target crossover from Gene Expression Omnibus (GEO) and public databases were used to identify potential biomarkers for HCC. Subsequently, validation and prognostic value analyses were performed using the Gene Expression Profile Interaction Analysis (GEPIA) platform. The Cytoscape software created a network of "compound targets" to pinpoint compounds linked to the biomarkers. Molecular docking techniques were utilized to validate the connection between these compounds and the identified biomarkers. Ultimately, the HepG2 liver cancer cell line was chosen to assess the inhibitory effect of Hederagenin (HDG) and to confirm the expression of ADH1B through Western blot analysis. In this study, four key biomarkers (NR1I2, ADH1B, NQO1, GHR) were identified. Molecular docking showed that these four core targets could form stable conformations with the corresponding compounds. As the drug concentration decreases, the inhibitory effect on HepG2 diminishes, and the survival rate of HepG2 cells significantly declines following the administration of 100 µmol/L HDG. Compared to the control, the expression of ADH1B protein is significantly increased in HepG2 cells treated with 100 µmol/L HDG. The study identified four key biomarkers (ADH1B, GHR, NQO1, NR1I2) that have prognostic ability for HCC. This study provides biomarkers and potential targeted monomeric medicines for treating HCC.

Peripheral immune signatures associated with the risk of hepatocarcinogenesis in cirrhotic Egyptian HCV patients before and after treatment with direct-acting antivirals.

Although direct-acting antivirals (DAAs) have revolutionized the management of chronic HCV, the debatable association with hepatocellular carcinoma (HCC) occurrence/recurrence has raised major concerns about their long-term use, especially in cirrhotic cases. The role of epithelial tight junction proteins (TJPs) in hepatocarcinogenesis has been highlighted; however, the association of their expression in peripheral blood mononuclear cells (PBMCs) with HCC has rarely been reported. This study aimed to explore the role of peripheral claudin (Cldn)1 in liver pathogenesis and its crosstalk with soluble immune mediators in HCC prognosis. The study population included six independent subgroups: healthy controls, cirrhotic/non-cirrhotic treatment-naïve HCV patients, DAA-SVR patients, and anticancer treatment-naïve de novo HCC patients. The laboratory tests included serum levels of alpha-fetoprotein (AFP), albumin, liver transaminases, total bilirubin, and CBC profiling. The serum levels of soluble cluster of differentiation (sCD)163, IL-10, and IL-12 were estimated by corresponding ELISA kits, whereas the levels of Cldn1 and transforming growth factor (TGF)-β in PBMCs were quantified using quantitative PCR (qPCR). Serum sCD163, IL-10, and IL-12 levels were significantly higher in the HCC patient group than in the control and non-malignant patient groups (P < 0.0001). No significant difference was detected in the serum levels of the three markers between cirrhotic and non-cirrhotic patients, whereas their levels were significantly different between cirrhotic and non-cirrhotic patients (P < 0.0001). Similarly, the transcriptional levels of peripheral Cldn1 and TGF-β were significantly higher in patients with HCC and non-malignant cirrhosis than in patients without cirrhosis (P = 0.0185-<0.0001 and 0.0089-<0.0001, respectively). Logistic regression analysis revealed a significant association between all the abovementioned markers and HCC (P = 0.0303 to < 0.0001), which was further confirmed by the results of receiver operating characteristic (ROC) analysis, which revealed an area under the curve (AUC) value ranging from 0.883 to 0.996. The calculated cutoff values demonstrated remarkable prognostic capacity, with ranges of 88-99.41% and 82.14-97.92% and positive/negative predictive values ranging from 84.62 to 98.3% and 92-98%, respectively. The proposed HCC predictors are novel non-invasive HCC biomarkers that maintain their predictive power under different pathological conditions and circumvent the drawbacks of conventional prognostic markers in patients with mild cirrhosis and/or normal AFP, albumin, and/or platelet counts.

Acid Sphingomyelinase Activation and ROS Generation Potentiate: Antiproliferative Effects of Mitomycin in HCC

Sphingolipids play a major role in the regulation of hepatocellular apoptosis and proliferation. We have previously identified sphingolipid metabolites as biomarkers of chronic liver disease and hepatocellular carcinoma. Human hepatocellular carcinoma cell lines were transfected with a plasmid vector encoding for acid sphingomyelinase. Overexpressing cells were subsequently treated with mitomycin and cell proliferation, acid sphingomyelinase activity, sphingolipid concentrations, and generation of reactive oxygen species were assessed. The stimulation of acid sphingomyelinase-overexpressing cell lines with mitomycin showed a significant activation of the enzyme (p &lt; 0.001) followed by an accumulation of various ceramide species (p &lt; 0.001) and reactive oxygen radicals (p &lt; 0.001) as compared to control transfected cells. Consequently, a significant reduction in cell proliferation was observed in acid sphingomyelinase-overexpressing cells (p &lt; 0.05) which could be diminished by the simultaneous application of antioxidant agents. Moreover, the application of mitomycin induced significant alterations in mRNA expression levels of ceramidases and sphingosine kinases (p &lt; 0.05). Our data suggest that the overexpression of the acid sphingomyelinase in human hepatoma cell lines enhances the in vitro antiproliferative potential of mitomycin via accumulation of ceramide and reactive oxygen species. The selective activation of acid sphingomyelinase might offer a novel therapeutic approach in the treatment of hepatocellular carcinoma.

Identification of alternative lengthening of telomeres-related genes prognosis model in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide, characterized by high mortality. This study aimed to explore the prognostic value and function of alternative lengthening of telomeres (ALT)-related genes in HCC. Differentially expressed genes (DEGs) were identified based on The Cancer Genome Atlas (TCGA) and then intersected with ALT-related genes to obtain ALTDEGs. Risk score model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression and validated with Gene Expression Omnibus (GEO) datasets. The predictive efficacy of the risk score and ALTs-score was evaluated by Kaplan-Meier curves, time-ROC curves, and the nomogram analyses. The impacts of SMG5 silencing on the HCC cell behaviors were assessed by CCK-8, wound healing, and Transwell assays. A total of 500 ALTDEGs were screened and 13 genes (CDCA8, SMG5, RAD54B, FOXD2, NOL10, RRP12, CCT5, CCT4, HDAC1, DDX1, HRG, HDAC2, and PPP1CB) were identified for constructing a prognostic model. The overall survival (OS) curves, time-ROC curves, and nomograms based on the risk score or ALTs-score were developed to optimally predict the survival of HCC patients. ALTs-score was correlated with immune infiltration and confirmed its value in predicting immunotherapy outcomes. Furthermore, RT-qPCR demonstrated that eight risk signature genes were up-regulated in HCC cells. SMG5 silencing suppressed the proliferation, migration, and invasion of HCC cells. It was also found that SMG5 silencing reduced C-circle level in SNU-387 cells. We identified new ALT-related prognostic biomarkers for HCC. SMG5 knockdown inhibited the HCC progression, which might be a promising target for HCC therapy.

Expression and clinical significance of PIKFYVE gene in hepatocellular carcinoma analyzed based on TCGA database and experimental validation

Objective: To investigate the expression and clinical significance of human FYVE finger-containing phosphoinositide kinase (PIKFYVE) in hepatocellular carcinoma (HCC) on the basis of cancer genome atlas (The cancer genome atlas, TCGA) database analysis and clinical samples experimental validation. Methods: Based on the data information of 424 clinical samples (including 374 cases of HCC tissues and 50 cases of nontumorous liver tissues) in the TCGA database, Cox regression analysis and Kaplan-Meier method were used to analyse the relationship between the PIKFYVE mRNA expression and the clinical characteristics, prognosis for survival of HCC patients. The relationship between the PIKFYVE gene and immune cell infiltration was examined by correlation analysis between the PIKFYVE gene and 24 immune cells. In addition, we analysed the correlation between the mRNA expression of PIKFYVE gene and RAC-alpha serine/threonine-protein kinase (AKT1), phosphatase and tensin homolog (PTEN), protein kinase C, alpha (PRKCA), inositol polyphosphate-5-phosphatase (INPP5D), phosphoinositide-3-kinase regulatory subunit 1(PIK3R1), Inositol Polyphosphate 4-phosphatase Type II (INPP4B) and phospholipase-C4 gene (PLCB4) in HCC tissues. Meanwhile, paraffin sections of highly differentiated, moderately differentiated, poorly differentiated, and nontumorous liver tissue in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University were collected, each of which was 30 cases, and the histopathological observation was carried out by HE staining, and the expression levels of PIKFYVE and Ki67 proteins were verified by immunohistochemistry in each clinical sample. Results: The expression level of PIKFYVE gene in HCC tumours was significantly higher than that in normal liver tissues (P=0.000 2, P<0.01), and the overall survival of patients in the low PIKFYVE expression group was significantly longer than that in the high expression group (HR=1.57, 95%CI: 1.10～2.25, P=0.014). The results of Univariate Cox regression analysis showed that there was an effect of TNM stage, pathological stage, tumour status and residual tumour on Overall survival (OS) (P<0.05), and the expression level of PIKFYVE had an effect on OS survival (P<0.05); the PIKFYVE prognostic risk model score ratio was HR=1.533 (1.077-2.181, P=0.018). Multivariate Cox regression analysis showed a PIKFYVE prognostic risk model score ratio HR=1.481 (0.886-2.476, P=0.134) and an area under the Receiver Operating Characteristic curve of 0.640, which was greater than 0.5, suggesting that the PIKFYVE prognostic risk model has a predictive value in survival prediction. Correlation analysis showed that the expression level of PIKFYVE was highly correlated with immune cell infiltration and TP53 (P<0.01). The immunohistochemistry staining results showed that the expression of PIKFYVE in HCC tissues was significantly higher than that of nontumorous tissues (P<0.05), and there was a negative correlation with the degree of differentiation. Conclusion: PIKFYVE, as an independent risk factor for HCC, is expected to be developed as a clinical diagnostic biomarker for HCC, which will provide a reference for new drugs for the treatment of HCC.

Deciphering the oncogenic potential of ADAM9 in hepatocellular carcinoma through bioinformatics and experimental approaches

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. This study investigates the role and mechanisms of ADAM9 as a biomarker and potential therapeutic target in HCC. Utilizing RNA-sequencing data and clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we conducted survival and meta-analyses, functional enrichment, and immune infiltration studies. Additionally, we evaluated the effects of ADAM9 silencing on HCC cell proliferation, migration, and invasion through in vitro experiments. Our results demonstrate that high ADAM9 expression is associated with poor prognosis and increased immune infiltration in HCC patients. Furthermore, ADAM9 knockdown significantly inhibited tumor cell proliferation and migration. These findings indicate that ADAM9 is a promising prognostic biomarker and potential therapeutic target in HCC. In conclusion, ADAM9 could offer avenues for developing strategies to inhibit tumor progression and improve patient outcomes.

The Prognostic Significance of Plasma Beta2-Glycoprotein I Levels in Hepatocellular Carcinoma Patients.

Beta2-glycoprotein I (β2-GPI) is a plasma glycoprotein with multiple physiological functions, but its relationship with hepatocellular carcinoma (HCC) is still poorly understood. HCC is one of the most common forms of liver cancer and is a leading cause of cancer-related death worldwide. This study aimed to investigate the association between β2-GPI and liver cancer and further validate its potential as a biomarker for HCC. Thirty-six patients diagnosed with HCC at the Division of Gastroenterology and Hepatology, E-Da Hospital, Taiwan, were included in the study. The expression levels of β2-GPI in plasma specimens from patients with HCC were determined by enzyme immunoassay and analyzed in relation to clinicopathological variables using the Chi-square test or Fisher's exact test. The predictive significance of β2-GPI for both overall survival (OS) and disease-free survival (DFS) was assessed using Kaplan-Meier estimates, and the statistical significance of differences was evaluated through the log-rank test. Cox proportional hazards regression models were used to evaluate the association between OS/DFS time and clinicopathological characteristics. Results: Plasma β2-GPI levels were significantly lower in patients with HCC compared to non-cancer controls and significantly correlated with aspartate aminotransferase (AST) levels of HCC. High plasma β2-GPI levels were significantly associated with better OS and DFS in HCC patients. Furthermore, in multiple variates analyses, OS was found to be significantly better in HCC patients with higher plasma β2-GPI expression. Elevated levels of β2-GPI protein in the plasma of HCC patients were identified as an independent factor predictive of improved OS and DFS. Activating β2-GPI in individuals at high risk could serve as a promising way for mitigating the progression of HCC.

Screening of cancer-specific biomarkers for hepatitis B-related hepatocellular carcinoma based on a proteome microarray

Hepatocellular carcinoma (HCC) is associated with one of the highest mortality rates among cancers, rendering its early diagnosis clinically invaluable. Serum biomarkers, specifically alpha-fetoprotein (AFP), represent the most promising and widely used diagnostic biomarkers for HCC. However, its detection rate is low in the early stages of HCC progression, and distinguishing specific false positives for other liver-related diseases, such as cirrhosis and acute hepatitis, remains challenging. Therefore, this study was conducted to identify biomarkers for hepatitis B (HBV)-related liver diseases by screening differentially expressed autoantibodies against tumor-associated antigens (TAAbs). We designed a large-scale multistage investigation, encompassing initial screening, HCC-focused, and ELISA validation cohorts to identify potential TAAbs in HBV-related liver diseases, spanning from healthy control (HC) individuals to patients with chronic hepatitis B (CHB), hepatitis B-related cirrhosis (HBC), and HCC, using protein microarray technology. The differential biological characteristics of TAAbs were analyzed using bioinformatics analysis. Validation of tumor-specific biomarkers for HCC was performed using ELISA. In the screening cohort, 547 candidate TAAbs were identified in the HCC group compared to those in the HC group. In the HCC-focused cohort, 64, 61, and 65 candidate TAAbs were identified in the CHB, HBC, and HCC groups, respectively, compared to those in the HC group. Thirty-four proteins exhibited continuously elevated expression from HCs to patients with CHB, HBC, and HCC. Among these, nine were identified as cancer-specific proteins. In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.

Circulating Galectin-3: A Prognostic Biomarker in Hepatocellular Carcinoma.

Galectin-3 plays critical roles in the adhesion, proliferation, and differentiation of tumor cells. Recent data have suggested that galectin-3 plays a role in the development of hepatocellular carcinoma (HCC); however, its prognostic value has not been validated. The aim of our study was to evaluate the clinical and prognostic value of galectin-3 in patients with HCC. We prospectively enrolled and collected clinicopathologic data and serum samples from 767 patients with HCC between 2001 and 2014 at The University of Texas MD Anderson Cancer Center. Two hundred patients without HCC were also enrolled and had data collected. The Kaplan-Meier method was used to estimate overall survival (OS) distributions. The median OS in this cohort was 14.2 months (95% CI, 12-16.1). At the time of analysis, the 1-year OS rate was 45% (95% CI, 0.4-0.51) among patients with high galectin-3 levels and 59% (95% CI, 0.54-0.63) among patients with low galectin-3 levels. OS was significantly inferior in patients with high galectin-3 levels than in patients with lower galectin-3 levels (median OS: 10.12 vs. 16.49 months; p = 0.0022). Additionally, the multivariate model showed a significant association between high galectin-3 level and poor OS (hazard ratio [HR] = 1.249; 95% CI, 1.005-1.554). Comparison between low ( n = 464 patients) and high ( n = 302 patients) galectin-3 levels showed that mean serum galectin-3 levels were significantly higher in patients with HCC who had hepatitis C virus (HCV) infection ( p = 0.0001), higher Child-Pugh score (CPS) ( p = 0.0009), and higher Cancer of the Liver Italian Program (CLIP) score ( p = 0.0015). Our study shows that serum galectin-3 level is a valid prognostic biomarker candidate.

Genes of DLK1-DIO3 Locus and miR-379/656 Cluster is a Potential Diagnostic and Prognostic Marker in Patients with Hepatocellular Carcinoma: A Systems Biology Study

BackgroundHepatocellular carcinoma is the sixth most common malignancy reported globally. This highlights the need for reliable biomarkers that can be employed for diagnostic and prognostic applications. The present study aimed to classify and characterize the clinical potential of DLK1-DIO3 and miR-379/656 cluster genes in hepatocellular carcinoma. MethodsWe extensively studied the clinical potential of DLK1-DIO3 genes through a comprehensive systems biology approach and assessed the diagnostic and prognostic potential of the genes associated with the region. Additionally, we have predicted the gene targets of the miR-379/656 cluster associated with the locus and have identified the gene ontology, pathway, and disease associations. ResultsWe report this region as a potential biomarker for hepatocellular carcinoma. About thirty clustered miRNAs, a long-non-coding RNA, and two coding genes of the region were underexpressed in tumors. ROC analysis identified 11 clustered miRNAs with diagnostic potential. Survival analyses identified MEG3 and the miR-379/656 cluster as prognostically significant. Further, the Random-Forest model predicted that the miRNA cluster classifies patients according to TNM staging. Furthermore, overrepresentation analysis identified several key pathways, molecular functions, and biological processes associated with the cluster gene targets. ConclusionOur study suggests that DLK1-DIO3 genes, miR-379/656 cluster, and its target gene network might be potential diagnostic and prognostic markers for HCC management and therapy.

High throughput sequencing reveals alterations in B cell receptor repertoires associated with the progression of hepatic cirrhosis to hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is developed as a consequence of chronic liver cirrhosis, and both diseases are difficult to diagnose and differentiate. Accurate noninvasive biomarkers for HCC and liver cirrhosis are urgently needed. Here we used high-throughput sequencing to characterize the B cell receptor (BCR) repertoires from 36 HCC tumor samples and 10 liver cirrhosis (LC) tissue biopsies to understand the immune alterations during hepatic carcinogenesis. The principal components analysis (PCA) showed that the pattern of BCR in HCC was distinct from that in LC. As measured by Clonality and Shannon indexes, the diversity of BCR repertoire was significantly lower in HCC than in LC (P < 0.01). Our results corroborated that the BCR diversity and composition could be closely correlated with hepatic carcinogenesis. And BCR repertoire may be used to predict the progression of HCC and design targeting immunotherapy in the near future.

Extracellular vesicles in hepatocellular carcinoma: unraveling immunological mechanisms for enhanced diagnosis and overcoming drug resistance.

Current research is focused on utilizing EVs as a biopsy tool to improve the diagnostic accuracy of HCC, reduce surgical risk, and explore their potential in modulating drug resistance and advancing immunotherapeutic strategies. Extracellular vesicles (EVs) have been increasingly recognized as important non-invasive biomarkers in hepatocellular carcinoma (HCC) due to the presence of a variety of biomolecules within them, such as proteins and RNAs, etc. EVs play a key role in the early detection, diagnosis, treatment, and prognostic monitoring of HCC. These vesicles influence the development of HCC and therapeutic response in a variety of ways, including influencing the tumor microenvironment, modulating drug resistance, and participating in immune regulatory mechanisms. In addition, specific molecules such as miRNAs and specific proteins in EVs are regarded as potential markers for monitoring treatment response and recurrence of HCC, which have certain research space and development prospects. In this paper, we summarize the aspects of EVs as HCC diagnostic and drug resistance markers, and also discuss the questions that may be faced in the development of EVs as markers.

Unveiling miRNA-Gene Regulatory Axes as Promising Biomarkers for Liver Cirrhosis and Hepatocellular Carcinoma.

Liver cirrhosis, a severe scarring condition of the liver with the potential to progress to hepatocellular carcinoma (HCC), necessitates the development of reliable biomarkers for early detection due to the asymptomatic nature of its early stages. Recent discoveries in microRNAs (miRNAs) hold promise for a noninvasive test, with the potential to significantly improve patient outcomes. Building upon these promising findings, this study investigates gene expression data, identifying distinct sets of DEGs and DEMs using GEO2R. Subsequently, a gene-miRNA network was constructed using Cytoscape to explore potential interactions between DEMs and their target genes (DEGs). Boxplot analysis was carried out to identify and validate differences in gene expression between healthy and diseased tissues. This analysis revealed four significantly differentially expressed genes: CAV1, PEA15, EMP1, and ENAH. Notably, subsequent survival analysis demonstrated that EMP1 and ENAH significantly impact overall patient survival. Intriguingly, the constructed network identified several potential regulatory axes: hsa-miR-191-5p/ENAH, hsa-miR-3158-3p/ENAH, hsa-miR-371a-5p/ENAH, and hsa-miR-6753-5p/EMP1. Crucially, a direct comparison of DEGs and DEMs between liver cirrhosis and HCC pinpointed AGO3, NCOA3, and TNPO1, along with their regulatory elements, as potential key drivers of HCC development in cirrhotic patients, underscoring their importance as targets for early diagnostic and therapeutic strategies. Finally, immunohistochemical (IHC) analysis not only validates our findings but also reiterates the novelty of the identified genes. Overall, elucidating the role of these novel genes and regulatory elements could pave the way for an earlier and more accurate diagnosis of liver diseases.

Serum laminin γ2 monomer as a predictive biomarker for hepatocellular carcinoma in patients with chronic hepatitis B virus infection: a retrospective cohort study

This retrospective study evaluated the use of laminin γ2 monomer (LG2m) as a predictive biomarker for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. Serum LG2m levels were measured in two cohorts of patients: cohort 1 comprised 56 patients with chronic liver disease for assessing LG2m stability, whereas cohort 2 included 89 patients with chronic HBV infection who did not have HCC for evaluating the usefulness of LG2m measurement in HCC prediction. LG2m was highly stable in cryopreserved serum, and an increased LG2m level was significantly associated with a higher risk of HCC in chronically HBV-infected patients (P = 0.012). Multivariable Cox regression analysis revealed that high LG2m was an independent significant risk factor for HCC (hazard ratio, 7.16; 95% confidence interval, 1.31–39.2; P = 0.023). These findings suggest that LG2m may serve as a useful biomarker for the prediction of future HCC in patients with chronic HBV infection.

Evaluation of glypican‑3 in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers occurring worldwide, including Mongolia. Although alpha-fetoprotein (AFP) is a widely used marker for HCC, conflicting studies have been published regarding its specificity and sensitivity towards HCC. Glypican-3 (GPC3) is a different promising biomarker for HCC, and there is some evidence to suggest that this protein may be a more specific marker compared with AFP. GPC3 has been shown to fulfill important roles in cell proliferation and division during embryogenesis, and is rarely found in the tissues of healthy adults. The aim of the present study was to investigate the levels of serum GPC3 (sGPC3) and tissue GPC3 in Mongolian patients with HCC. Serum samples from a total of 270 individuals [HCC group, 90 patients; risk group (RG), 90 subjects; and control group, 90 subjects] were evaluated using enzyme-linked immunosorbent assay to identify the sGPC3 levels. In addition, immunohistochemical analysis of the GPC3 was performed on tissue samples from 50 patients with HCC to evaluate the expression of GPC3. sGPC3 level was found to be significantly increased in the HCC group compared with the RG and the control group, with the area under the curve=0.85 (P<0.001). sGPC3 was found to be significantly associated with hepatitis C virus status and cirrhosis (P<0.05). In addition, the tissue expression of GPC3 was associated with the serum AFP (sAFP) level. Finally, positive staining of GPC3 was observed when the sAFP level of the patient was >20 ng/ml. In conclusion, the results from the present study have supported that GPC3 may be a promising marker for HCC, and can be used as a diagnostic marker alongside AFP.

Glycomics as prognostic biomarkers of hepatocellular carcinoma: A systematic review.

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, which is associated with a low 5-year survival rate. The importance of effective disease monitoring and prognostic evaluation is undeniable. For the present study, a systematic review was performed using extensive searches in Medline, Embase, Web of Science and Scopus up to December 29, 2023. The aim of the present study was to examine whether N-glycomics could predict the risk of developing HCC in adults with chronic liver disease and, if HCC was present, predict overall survival. As a secondary outcome, the prediction capability of HCC recurrence was assessed. After deduplication, 3,904 studies were identified, of which 30 were included. Overall, the median size of the study cohort was 144 patients, with a median follow-up time of 63.6 months. Three studies explored N-glycomics in whole serum, whereas the rest focused on individual glycoproteins, with Mac-2 binding protein glycosylation isomer (M2BPGi) being the most commonly studied. Most articles investigated baseline M2BPGi values as predictors for the development of HCC and demonstrated a median area under the curve of 0.83 with a cut-off index value of 1.8. In conclusion, it was revaled that N-glycan changes exhibit added value in determining patient prognosis in terms of survival, monitoring HCC development and recurrence.

Detection and validity of long non-coding RNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 as biomarkers for hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers in the world. Long noncoding RNAs (lncRNAs) could contribute significantly to HCC development through diverse mechanisms, such as the recruitment of many regulatory protein complexes. This study aimed to evaluate the expression levels of the lncRNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 in liver cirrhosis and HCC and also assess their diagnostic performance as biomarkers for HCC. MethodsIn total, 180 participants were in this study, classified into three groups (60 participants in each): Group I (hepatocellular carcinoma patients), Group II (liver cirrhosis patients), and Group III (apparently healthy individuals). The expressions of the HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were detected using a reverse-transcriptase real-time polymerase chain reaction (qRT-PCR). ResultsThe expression levels of HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were markedly increased in the HCC patients compared with those in the cirrhotic patients and controls. They also exhibited greater sensitivity as diagnostic biomarkers than alpha-fetoprotein. ConclusionsThe HOTAIR, HOST2, HOXA-AS2, and MALAT1 lncRNAs exhibit promising potential as valuable diagnostic biomarkers of HCC and in differentiating HCC from liver cirrhosis. Furthermore, combining alpha-fetoprotein can yield higher accuracy.

Female and diabetes are risk factors for alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II negative in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common type of tumor with a high incidence. Alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II or des-gamma-carboxy prothrombin) are proven effective biomarkers for HCC. Combining them can enhance detection rates. However, when both AFP and PIVKA-II are negative, clinical diagnosis may be missed. This study aims to explore the risk factors for AFP and PIVKA-II negativity in HCC, thereby reducing missed diagnoses. A retrospective study enrolled 609 HCC patients at Shandong Public Health Clinical Center Affiliated with Shandong University from January 2010 to March 2022. Patients with negative AFP and PIVKA-II were the observed group, and others with at least 1 positive were controls. Epidemiological, clinical, laboratory, and radiological data were collected and analyzed to identify the frequency and factors influencing AFP and PIVKA-II negativity. Receiver operating characteristic (ROC) curves were used to assess the prediction model's ability to detect negative AFP and PIVKA-II in HCC. Gender (P = .045, 95% confidence interval [95%CI] = 1.013-3.277), diabetes mellitus (P = .018, 95%CI = 1.151-4.422), tumor size (P = .000, 95%CI = 0.677-0.841), glutamate transpeptidase (P = .003, 95%CI = 0.239-0.737), total bilirubin (P = .001, 95%CI = 0.235-0.705), and hepatitis B virus-associated infections (P = .007, 95%CI = 0.077-0.661) were significantly associated with AFP and PIVKA-II negativity in HCC. The prediction model had an area under curve of 0.832 (P < .001, 95%CI = 0.786-0.877), with a sensitivity of 81.2% and specificity of 75.5% in all HCC patients. Female diabetic patients with levels closer to normal for glutamate transpeptidase and total bilirubin are more likely to develop AFP and PIVKA-II-negative HCC. Imaging is crucial for screening liver cancer in these patients.

TMEM209 promotes hepatocellular carcinoma progression by activating the Wnt/β-catenin signaling pathway through KPNB1 stabilization

Hepatocellular carcinoma (HCC) is the most common malignancy in the liver, with a poor prognosis. Transmembrane protein 209 (TMEM209) involves multiple biological processes, such as substance transportation and signal transduction, and is abundantly expressed in tumor tissues. However, the relationship between TMEM209 and HCC has not been comprehensively elucidated. In this study, we aimed to illustrate this issue by in vitro and in vivo experiments. Bioinformatic analysis and clinical sample validation revealed that TMEM209 was upregulated in HCC and correlated with reduced survival duration. Functionally, TMEM209 promoted the proliferation, migration, invasion, and EMT of HCC cells in vitro and facilitated tumor growth and metastasis in xenograft models. Mechanistically, TMEM209 promoted the proliferation and metastasis of HCC in a KPNB1-dependent manner. Specifically, TMEM209 could bind to KPNB1, thereby competitively blocking the interaction between KPNB1 and the E3 ubiquitin ligase RING finger and CHY zinc finger domain-containing protein 1 (RCHY1) and preventing K48-associated ubiquitination degradation of KPNB1. Ultimately, the Wnt/β-catenin signaling pathway was activated, contributing to the progression of the malignant phenotype of HCC. In conclusion, the molecular mechanism underlying the TMEM209/KPNB1/Wnt/β-catenin axis in HCC progression was elucidated. TMEM209 is a potential biomarker and therapeutic target for HCC.

The potential role of Circular RNA New biomarkers for the prognosis of hepatocellular carcinoma

Abstract Introduction/Objective Hepatocellular carcinoma (HCC) is the most commonly diagnosed cancer with related deaths worldwide. The non-coding RNAs as the functions of circRNAs in tumor progression have attracted great attention to the clinicopathological characteristics of HCC. Methods/Case Report The present study was conducted to investigate and evaluate the expression level of hsa_circ_2124, and hsa_circ_4018 downstream target gene pathways related to clinico-pathological parameters of HCC. Cell proliferation was examined by West-1 assay and protein expression levels by using western blotting analysis. Results (if a Case Study enter NA) The hsa_circ_2124 expression level was up-regulated in HepG2 and Hep3B cells, respectively compared to normal liver cells. Furthermore, hsa_circ_4018 was down-regulated in two HCC cell lines compared to the normal cell line (LO2 cells), demonstrating the heterogeneity characteristics of the circRNA expressions in different HCC cell lines. Our data showed a significant inhibition of hsa_circ_4018 in HCC cell lines which in turn inhibited cell proliferation and migration. Besides, there is an inhibition in cell proliferation after hsa_circ_2124 knockdown in the tested cell lines. In addition, our data reported that the Knockdown of hsa_circ_2124 reduced the expression of ERK, c-Myc, and β-catenin expression in Hep-G2 cells. Furthermore, hsa_circ_4018 showed significant inhibition in β-catenin and c-Myc expression levels in Hep3B cells compared to the control. The knockdown of hsa_circ_2124 induced G1-phase arrest in HepG2 cells compared to control, suggesting the role of hsa_circ_2124 in the inhibition of HCC progression. Conclusion All in all, our data revealed that hsa_circ_2124 or hsa_circ_4018 plays a role in the regulation of MAPK and Wnt/β-catenin signaling pathways, which might be potential therapeutic biomarkers for HCC.