Marker For Hepatocellular Carcinoma Research Articles

Molecular and immune landscape of hepatocellular carcinoma for therapeutic development.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with an estimated 750,000 deaths in 2022. Recent emergence of molecular targeted agents (MTAs) and immune checkpoint inhibitors (ICIs) and their combination therapies have been transforming HCC care, but their prognostic impact in advanced-stage disease remains unsatisfactory. In addition, their application to early-stage disease is still an unmet need. Omics profiling studies have elucidated recurrent and heterogeneously present molecular aberrations involved in pro-cancer tumor (immune) microenvironment that may guide therapeutic strategies. Recurrent aberrations such somatic mutations in TERT promoter and TP53 have been regarded undruggable, but recent studies have suggested that these may serve as new classes of therapeutic targets. HCC markers such as alpha-fetoprotein (AFP), glypican-3 (GPC3), and epithelial cell adhesion molecule (EpCAM) have also been explored as therapeutic targets. These molecular features may be utilized as biomarkers to guide the application of new approaches as companion biomarkers to maximize therapeutic benefits in patients who are likely to benefit from the therapies, while minimizing unnecessary harm in patients who will not respond. The explosive number of new agents in the pipelines have posed challenges in their clinical testing. Novel clinical trial designs guided by predictive biomarkers have been proposed to enable their efficient and cost-effective evaluation. These new developments collectively facilitate clinical translation of personalized molecular-targeted therapies in HCC and substantially improve prognosis of HCC patients.

The fabrication of phosphotungstate@UIO-Au/reduced graphene oxidation for electrochemical ultrasensitive detection of alpha-fetoprotein.

As an early multi-purpose tumor marker of hepatocellular carcinoma, alpha-fetoprotein (AFP) plays a vital role in early diagnosis and treatment. To achieve the early and accurate determination of AFP, the POMOF was fabricated by embedding H3PW12O40 (PW12) into UIO-66-NH2, further immobilized on reduced GO (rGO) and fabricated an innovative POMOF nanocomposite (PW@UIO-Au/rGO) as an electrochemical immunosensor (ECI-sensor). The PW@UIO-Au/rGO achieved 17-fold signal enhancement owing to their synergistic effect, enabling PW@UIO-Au/rGO exhibit high oxidase-like catalytic activity, facilitating their sensing performance. Under optimal experimental conditions, the proposed PW@UIO-Au/rGO ECI-sensor presented excellent sensing performance over a wide range from 0.01 ng mL-1 to 500 ng mL-1 with ultra-low detection of 4.0 pg mL-1. Notably, sensing results in real serum samples were verified by the clinical enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence immunoassay (ECL) methods with excellent accuracy and consistency, indicating the excellent environmental tolerance of the proposed ECI-sensor. This work provided a promising strategy for designing feasible ultra-sensitive probe for sensing AFP in clinical test.

Preoperative prediction of Ki-67 expression in hepatocellular carcinoma by spectral imaging on dual-energy computed tomography (DECT).

The Ki-67 expression level, which represents the proliferation status of cells, serves as a prognostic marker for hepatocellular carcinoma (HCC); however, the immunochemistry method currently used to evaluate Ki-67 is invasive and is not suitable for patients who have lost the chance for surgery, such as those with advanced tumors or those with other serious organic diseases. This study aimed to investigate the value of quantitative dual-energy computed tomography (DECT) parameters in predicting the expression level of Ki-67 in HCC. This study analyzed the data of 123 consecutive patients with HCC who underwent both Ki-67 immunohistochemistry analysis and two-phase contrast-enhanced DECT imaging. The patients were divided into the following two groups based on the positive rate of Ki-67 (Ki-67%): the high-expression group (Ki-67% >20%, n=74); and the low-expression group (Ki-67% ≤20%, n=49). The computed tomography (CT) values in the 130 and 140 keV monochromatic energy images (HU130-140keV), normalized effective atomic number (NeffZ), fat density (Dfat), and water density (Dwater) were measured and calculated at the arterial phase (AP) and portal venous phase (PVP). A Spearman correlation coefficient analysis, a comparison of parameters between groups, a receiver operating characteristic (ROC) curve analysis for evaluating predictive efficacy, and a multivariable logistic regression analysis were conducted. The NeffZ-AP, HU130 keV-PVP, HU140 keV-PVP, Dfat-PVP, and Dwater-PVP were positively correlated with the Ki-67% (all P<0.05), and the DECT parameter values in the high-expression group were significantly higher than those in the low-expression group (all P<0.05). The Dwater-PVP [odds ratio (OR) =1.353, 95% confidence interval (CI): 1.204-1.521, P<0.001] and tumor diameter (OR =1.258, 95% CI: 1.08-1.465, P=0.003) were independent predictive factors for high Ki-67 expression. Dwater-PVP had the highest predictive efficacy with an area under the curve (AUC) of 0.810. The multivariable analysis combining the DECT parameters and morphological characteristics improved the predictive efficacy of the model in predicting high Ki-67 expression (AUC =0.857). DECT provides a non-invasive method to evaluate the proliferation status of HCC cells, and the predictive efficacy of high Ki-67 expression could be improved by combining DECT parameters and morphologic features.

SLC1A3 is a novel prognostic biomarker associated with immunity and EMT in hepatocellular carcinoma

PurposeSolute carrier family 1 member 3(SLC1A3), a member of the glutamate transporter family, is implicated in the progression of gastric carcinoma and the renewal of thyroid carcinoma stem cells. The purpose of this work is to use experimental validation and bioinformatics analysis to look at the possible involvement of SLC1A3 in hepatocellular carcinoma (HCC).Materials and methodsWe examined the levels of SLC1A3 within HCC and its implications on immunological and epithelial–mesenchymal transition (EMT) features using the TCGA, ImmPort, and Molecular Signatures databases. The relationship between drug sensitivity and SLC1A3 expression was investigated using the GDSC database. Real-time quantitative polymerase chain reaction (qRT-PCR), Western blotting (WB), and cellular function assays were performed to assess SLC1A3 expression and its carcinogenic effects in HCC.ResultsAccording to our research, SLC1A3 overexpression in HCC is associated with a poor prognosis. Elevated levels of SLC1A3 promote HCC cell motility and invasion and can affect the prognosis of HCC by modifying immune responses and epithelial–mesenchymal transition. SLC1A3 has emerged as a novel prognostic marker in HCC and is associated with resistance to certain antitumor drugs.ConclusionSLC1A3 functions as a cancer-promoting factor contributing to poor HCC prognosis by affecting immune cell infiltration and regulating the EMT process. Elevated SLC1A3 expression may also serve as a predictor of treatment response to specific antitumor drugs.

Non-Coding RNAs as Potential Diagnostic/Prognostic Markers for Hepatocellular Carcinoma.

The increasing incidence of hepatocellular carcinoma (HCC), together with the poor effectiveness of the available treatments, make early diagnosis and effective screening of utmost relevance. Liquid biopsy represents a potential novel approach to early HCC detection and monitoring. The identification of blood markers has many desirable features, including the absence of any significant risk for the patients, the possibility of being used as a screening tool, and the ability to perform multiple tests, thus allowing for the real-time monitoring of HCC evolution. Unfortunately, the available blood markers for HCC have several limitations, mostly related to specificity and sensitivity. In this context, employing non-coding RNAs (ncRNAs) may represent an interesting and novel diagnostic approach. ncRNAs, which include, among others, micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), regulate human gene expression via interactions with their target mRNA. Notably, their expression can be altered in HCC, thus reflecting disease status. In this review, we discuss some notable works that describe the use of miRNAs, lncRNAs, and circRNAs as HCC biomarkers. Despite some open aspects related to ncRNA use, the presented works strongly support the potential effectiveness of these molecules as diagnostic/prognostic markers for HCC.

Serum amyloid A level as a marker of hepatocellular carcinoma in HCV-induced liver cirrhosis

Serum amyloid A level as a marker of hepatocellular carcinoma in HCV-induced liver cirrhosis

SLC41A1 overexpression correlates with immune cell infiltration in HCC and promotes its malignant progression.

Solute carrier 41 (SLC41) has been identified as a family of magnesium (Mg2+) transporters that participate in various diseases, including tumor development and progression. Recent studies revealed SLC41A3 acted as an oncogene and predicted poor survival for hepatocellular carcinoma (HCC) patients. However, the potential function of SLC41A1 in HCC remains unclear. In our study, we focused on the levels and putative mechanisms of SLC41A1 in HCC. Using bioinformatics techniques, we found SLC41A1 was upregulated in HCC, which was verified by immunostaining of HCC patients. SLC41A1 was correlated with clinicopathological characteristics, and could be utilized as independently diagnostic and prognostic markers for HCC. By exploring MethSurv website, DNA methylation was identified in SLC41A1, and several methylated CpG sites might affect overall survival of HCC patients. Using Gene Ontology (GO) , Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), protein-protein interaction (PPI) network, we found SLC41A1 overexpression was related to several tumor-promoting pathways and molecules, such as degradation of extracellular matrix, cell adhesion and O-linked glycosylation, and expression of CXCL1, CXCL5 and MUC1. The results of single-sample GSEA (ssGSEA) showed SLC41A1 might regulate infiltration of multiple immune cells, resulting in the imbalance between immune suppression and immune surveillance. Cellular experiments showed that knockdown of SLC41A1 inhibited proliferation, migration and invasion of HCC, whereas SLC41A1 overexpression exerted the tumor-promoting effects. Collectively, our results shed light on new insights into expression, putative roles and mechanisms of SLC41A1 in HCC, providing novel diagnostic biomarkers and therapeutic targets for HCC.

Unveiling Tim-3 immune checkpoint expression in hepatocellular carcinoma through abdominal contrast-enhanced CT habitat radiomics.

Immune checkpoint inhibitors (ICIs) are important systemic therapeutic agents for hepatocellular carcinoma (HCC), among which T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3) is considered an emerging target for ICI therapy. This study aims to evaluate the prognostic value of Tim-3 expression and develop a predictive model for Tim-3 infiltration in HCC. We collected data from 424 HCC patients in The Cancer Genome Atlas (TCGA) and data from 102 pathologically confirmed HCC patients from our center for prognostic analysis. Multivariate Cox regression analyses were performed on both datasets to determine the prognostic significance of Tim-3 expression. In radiomics analysis, we used the K-means algorithm to cluster regions of interest in arterial phase enhancement and venous phase enhancement images from patients at our center. Radiomic features were extracted from three subregions as well as the entire tumor using pyradiomics. Five machine learning methods were employed to construct Habitat models based on habitat features and Rad models based on traditional radiomic features. The predictive performance of the models was compared using ROC curves, DCA curves, and calibration curves. Multivariate Cox analyses from both our center and the TCGA database indicated that high Tim-3 expression is an independent risk factor for poor prognosis in HCC patients. Higher levels of Tim-3 expression were significantly associated with worse prognosis. Among the ten models evaluated, the Habitat model constructed using the LightGBM algorithm showed the best performance in predicting Tim-3 expression status (training set vs. test set AUC 0.866 vs. 0.824). This study confirmed the importance of Tim-3 as a prognostic marker in HCC. The habitat radiomics model we developed effectively predicted intratumoral Tim-3 infiltration, providing valuable insights for the evaluation of ICI therapy in HCC patients.

Fibroblast Heterogeneity in Hepatocellular Carcinoma and Identification of Prognostic Markers Based on Single-cell Transcriptome Analysis.

HCC is a malignant tumor with high morbidity and mortality. Fibroblasts play a key role in the tumor microenvironment (TME). However, the transcriptional regulatory mechanisms of fibroblasts remained unclear in HCC. The aim of this study was to explore the complex role of fibroblasts in hepatocellular carcinoma (HCC) and to reveal their transcriptional regulatory mechanisms. The goal of this study was to discover potential prognostic markers for HCC by analyzing the genetic variations and differentiation process of fibroblasts. Single-cell transcriptome data from the non-tumor liver site and primary tumor site of HCC were acquired from GSE149614, processed, and clustered using the Seurat pipeline. The inferCNV algorithm was applied to infer copy number variations (CNVs) in fibroblasts. Subsequently, the mechanism underlying the interaction between fibroblasts and other cells in the TME of HCC was analyzed using CellChat software. The trajectory of cellular differentiation of fibroblasts from normal state to malignant state was examined using Monocle 2. SCENIC analysis was performed to identify key transcription factors (TFs) in fibroblasts and assess their correlation with HCC prognosis. Finally, qRT-PCR and Transwell assays were carried out to analyze the mRNA expression and cell metastasis. We identified a total of nine different cell types (B cells, cycling cells, endothelial cells, epithelial cells, fibroblasts, hepatocytes, macrophages, plasma cells, and T cells) based on the single-cell transcriptomic data of HCC. Among them, fibroblasts were highly enriched at the primary tumor site, and their number increased with advanced stages. In addition, significant deletions were detected on chromosome 6p of fibroblasts, and genes in this region were remarkably enriched in pathways associated with antigen processing and presentation. Intercellular communication showed that epithelial cells regulated fibroblasts the most. The differentiation of fibroblasts was mainly accompanied by a transition from normal to malignant state. Importantly, CEBPD and FOSB, the TFs most associated with the putative timing of fibroblasts, were under-expressed in human hepatocytes and showed a significant correlation with HCC prognosis. Overexpressed CEBPD inhibited HCC cell migration and invasion. In conclusion, our study revealed that fibroblast recruitment and differentiation, as well as copy number loss at chromosome 6p, were associated with a higher degree of malignancy and immune dysfunction in HCC. The current discoveries provided new insights into the clinical treatment and diagnosis of HCC.

Regulatory Role of Long Noncoding RNAs LINC00449 in Hepatocellular Carcinoma Mechanism and Prognosis Via Sponge miR-329-3p/KIF5A Axis.

Hepatocellular carcinoma (HCC) is a globally prevalent malignant tumor with high recurrence and mortality rates. Long noncoding RNAs (lncRNAs) have been utilized to investigate the progression of various cancers, including HCC. The objective of this research is to explore the mechanism and prognostic impact of lncRNA LINC00449 on HCC. LINC00449 and miR-329-3p levels in HCC were measured using RT-qPCR. The impact of high- or lowLINC00449 expression on survival was tested. CCK-8, plate cloning, flow cytometry, and Transwell assays were selected to assess the biological functions of HCC cells. Kaplan-Meier and multivariate Cox analyses were conducted to evaluate the potential of LINC00449 as a prognostic marker for HCC. The interaction between LINC00449, miR-329-3p, and KIF5A was investigated through luciferase activity assays. LINC00449 expression in HCC tissues was increased. Silencing of LINC00449 improved the survival prospects of patients with HCC. Moreover, LINC00449 targeting the miR-329-3p/KIF5A axis influences the progression of HCC. LINC00449 may become a biomarker for the prognosis of HCC, and the LINC00449/miR-329-3p/KIF5A regulatory network mediates the deterioration of HCC.

Role of Serum Alpha-fetoprotein in Assessing the Resectability of Hepatocellular Carcinoma

Background: Serum AFP is a well-established tumor marker of hepatocellular carcinoma (HCC) which has already proved its acceptability in confirming the diagnosis and predicting the prognosis of HCC. Objective: The current study is aimed to evaluate the role of serum alpha-fetoprotein in assessing the resectability of HCC. Methods: This was a single-center, cross-sectional study done from September 2020 to August 2021 at the department of Hepatobiliary, pancreatic, and liver transplantation surgery at BSMMU. A total of 27 HCC patients who met the inclusion criteria were enrolled in the study. Clinical, laboratory, and imaging findings were obtained using a standardized data collecting sheet with the patients' informed agreement. AFP was measured by automated chemiluminescence analyzer (LIAISON XL, DiaSorin, Italy) in the Department of Biochemistry &amp; Molecular Biology, BSMMU. Based on the ROC curve of this study, the patients were divided into group 1 with AFP levels 38.45 ng/ml and group 2 with AFP levels &gt;38.45 ng/ml. According to the resectable criteria (TNM stage: I, II, BCLC stage: 0, A, B, CTP grade: A, B, ECOG PS: 0) established for the study, each AFP group was further subdivided into resectable and unresectable subgroups. Finally, the parameters (tumor size, number, location, CTP grade, fibrosis score, performance status, HBV positive, HBV DNA, BCLC and TNM stage) of the resectable and unresectable patients in each AFP group were evaluated. Statistical analyses were performed using SPSS version 22. Quantitative variables were expressed as mean±standard deviation and examined using an unpaired t-test. The qualitative data were represented by frequencies and percentages, and the Chi-Square test and Fisher exact test (where applicable) were used to determine any correlation. The statistical tests were conducted with a 95% confidence interval, and P0.05 was deemed statistically significant. Results: In this study, thirty seven percent (37%) patients ...........

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.

Nlrp6 overexpression inhibits lipid synthesis to suppress proliferation of hepatocellular carcinoma cells by regulating the AMPK-Srebp1c axis

To investigate the mechanism of Nlrp6 for regulating hepatocellular carcinoma (HCC) progression in light of lipid synthesis regulation. Nlrp6 expression level in HCC tissues of different pathological grades was investigated using RNA-seq data from The Cancer Genome Atlas (TCGA) database, and its correlation with the patients' survival was analyzed with Kaplan-Meier survival analysis. HepG2 cells with adenovirus-mediated Nlrp6 overexpression or knockdown were treated with palmitic acid (PA), and the changes in lipid deposition and cell proliferation were evaluated using Oil Red O staining, CCK-8 assay, EdU staining, and colony formation assay. RT-qPCR and Western blotting were used to detect the changes in expression of lipid synthesis-related genes and the proteins in the AMPK-Srebp1c axis. In a mouse model of hepatic steatosis established in liver-specific Nlrp6 knockout mice by high-fat diet feeding for 24 weeks, liver fibrosis was examined with histological staining, and the changes in expressions of HCC markers and the AMPK-Srebp1c signaling pathway were detected. Nlrp6 expression was significantly reduced in HCC tissues with negative correlations with the pathological grades and the patients' survival (P < 0.0001). In HepG2 cells, Nlrp6 overexpression significantly inhibited lipid deposition and cell proliferation, whereas Nlrp6 knockdown produced the opposite effects. Nlrp6 overexpression strongly suppressed the expression of lipid synthesis-related genes, promoted AMPK phosphorylation, and inhibited Srebp1c expression. The mice with liver-specific Nlrp6 knockout and high-fat feeding showed increased hepatic steatosis, collagen deposition, and AFP expression with reduced AMPK phosphorylation and increased Srebp1c expression. Nlrp6 overexpression inhibits lipid synthesis in HCC cells by regulating the AMPK-Srebp1c axis, which might be a key pathway for suppressing HCC cell proliferation.

Thrombospondin 2 as a Predictive Biomarker for HCC inHepatitis C Patients: A Longitudinal Study Following DAA Therapy.

This multicentre study investigated the dynamics of thrombospondin 2 (TSP2) levels during direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV) infected patients and evaluated TSP2's potential as a predictive marker for hepatocellular carcinoma (HCC). All 134 participants achieved sustained virological response at 12 weeks (SVR12) with DAA therapy, and serum TSP2 levels significantly decreased from before and after treatment (p < 0.001). During the median follow-up period of 6.0 years, HCC after DAA therapy was observed in 16 patients (11.9%). Patients with serum TSP2 High (≥ 32 ng/mL) at SVR12 had a significantly higher cumulative occurrence of HCC than did those without (26.5% vs. 7.0%, p = 0.0033). A multivariate Cox proportional hazards model identified male gender (HR 4.84, p = 0.005), HCC history (HR 4.61, p = 0.017) and TSP2 High (HR 3.93, p = 0.009) as significant independent predictors of HCC occurrence after DAA therapy. The model had a high concordance index of 0.878. Additionally, combining TSP2 High and FIB-4 High (≥ 3.538) at SVR12 yielded high specificity and negative predictive value (0.941 and 0.917, respectively) for predicting HCC. Kaplan-Meier analysis showed a higher HCC incidence in the TSP2 High + FIB-4 High group (log-rank p < 0.0001). In conclusion, TSP2 may be a promising biomarker for personalised HCC surveillance in DAA-treated hepatitis C patients.

Study of role of melanoma-associated antigen D1 (MAGE-D1) in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) ranks as the fifth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Current serum biomarkers for HCC surveillance and early diagnosis, particularly alpha-fetoprotein (AFP) the most commonly used marker, lack satisfactory sensitivity and specificity, highlighting an urgent need for more effective markers with higher accuracy for early HCC detection. The downregulation of melanoma-associated antigen D1 (MAGE-D1) transcription plays a crucial role in apoptosis and inhibits cancer cell proliferation when expressed ectopically. Moreover, reduced MAGE-D1 expression correlates with improved prognosis in many cancers. Therefore, this study aims to evaluate the diagnostic role of MAGE-D1 in HCC, proposing it as a novel biomarker for early diagnosis and monitoring of tumor progression. Serum MAGE-D1 expression was measured using RT-qPCR on 198 subjects, divided into three groups: 88 with HCC, 56 with chronic liver conditions, and 54 as healthy controls. With a sensitivity of 93.3% and a specificity of 97.5%, MAGED-1 shows strong potential as a diagnostic marker for HCC. The performance of serum MAGED-1 expression in discrimination between HCC and chronic liver condition revealed an area under the curve (AUC) of 0.939 using the cutoff (0.752) yielded a sensitivity of 90%, specificity of 85%, and an accuracy of 91%. Evaluation of the diagnostic significance of MAGED-1 demonstrated an AUC value of 0.726, with a sensitivity of 63.6% and a specificity of 73.5%. In conclusion, MAGED-1 might be a specific and sensitive biomarker for HCC, potentially improving the malignancy diagnosis and prognosis.

Diagnostic Value of Glypican 3 as a Marker of Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

Abstract Background Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third cause of cancer-related mortality world-wide. Early detection improves survival, and several HCC biomarkers have been studied for this purpose. However, aside from alpha- fetoprotein (AFP), none have entered broad clinical use globally. Aim of the Work to assess the diagnostic value of Glypican 3 as a marker of hepatocellular carcinoma in Egyptian cirrhotic patient. Patients and Methods This study is a comparative case control study. The period of the study is a 6th months. Post viral cirrhotic Egyptian patients treated in Ain Shams University hospitals. The study will be conducted on 60 Egyptian Cirrhotic patients with HBV OR HCV infection with or without HCC treated in Ain Shams University Hospitals Results In our study, The AFP level was significantly higher in high group [1700 (1122 – 5200)] than low group [700 (100 – 855)] and also significantly higher in both low and high groups than control group [2.6 (1.7 – 3.6)] and cirrhotic group [3.4 (1.5 – 5.8)] with p-value &amp;lt;0.001 and with no difference between cirrhotic and control. Regarding serum Glypican 3 which is the new marker addressed in this study, show that The GP3 level was significantly higher in low group [6.4 (5.6 – 7.53)] and high group [6.21 (5.16 – 7.98)] than control group [1.38 (1.22 – 1.54)] and cirrhotic group [1.65 (1.22 – 6.18)] with p-value &amp;lt;0.001 and with no difference between cirrhotic and control. In our study, there was statistically significant positive correlation found between GP3 level, total and direct bilirubin with (p value 0.004, 0.001) which is agreed with many studies as A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Conclusion Serum Glypican 3 level was significantly higher in patients with HCC regardless of other characteristics as presence of combined conditions as DM and HTN or Viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. Using of Glypican 3 will improve the diagnostic field and can help in early detection of HCC in surveillance programs Together with AFP. Glypican 3 can be used as prognostic factor and predictor of mortality from oesphogeal bleeding in patients with HCC

Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients with Chronic Hepatitis B or C Infection

Abstract Background Hpatocellular carcinoma HCC is now the sixth most common cause of cancer worldwide. The second leading cause of cancer death after lung cancer in men is HCC. The most frequently used screening tests for HCC patients are hepatic ultrasound (US) with or without assessment of alpha-fetoprotein, but the diagnostic value of AFP is recently challenged due to its low sensitivity and specificity. So the aim of this study was to evaluate the role of mac 2 as a diagnostic marker in HCC Egyptian patients. Objective This study will assess the role of Mac-2 Binding Protein Glycosylation Isomer as a Hepatocellular Carcinoma Marker in Patients With Chronic Hepatitis B or C Infection. Patients and Methods This study had been carried out on 70 subjects, age range more than 18 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain Shams university hospitals from august 2022 to june 2023, after informed consent were taken from the patients Results This study was carried out on 70 participants divided into 2 group: 35 patient post viral cirrhotic patients with Hepatocellular Carcinoma, 35 patient post viral cirrhotic patients without hepatocellar Carcinoma selected from Ain Shams university hospitals, after informed consent were taken from the patients. Subjects were divided as follow: Group A (Hcc): 35 patients with Hepatocellular carcinoma, More than 18 years. Group B (Cirrhotic): 35 patients with liver cirrhosis without Hepatocellular carcinoma, age more than 18 years Conclusion We concluded from this study that: Serum Mac2 level was significantly higher in patients with HCC regardless of other characteristics as presence of combined conditions as DM and HTN or Viral markers and mildly elevated in patients with liver cirrhosis compared to HCC group. MAC 2 is more sensitive than AFP in differentiation between HCC and cirrhoitic patients but AFP is more specific. Using of mac 2 will improve the diagnostic field and can help in early detection of HCC in surveillance programs Together with AFP.

Serum Myostatin Predicts the Risk of Hepatocellular Carcinoma in Patients with Alcoholic Cirrhosis: A Multicenter Study

Abstract Background Sarcopenia, characterized by age-related muscle loss, is common in patients with liver cirrhosis (LC). LC's metabolic burdens include protein and energy metabolism disorders, potentially leading to secondary sarcopenia. This study explores the prognostic role of serum myostatin levels in predicting hepatocellular carcinoma (HCC) development in individuals with alcoholic liver cirrhosis (ALC). Aim of the Work The aim of this study is to investigate the prognostic performance of serum myostatin levels on HCC development in patients with alcoholic liver cirrhosis (ALC). Patients and Methods We conducted a retrospective observational study using stored serum samples from a single center. We analyzed serum myostatin levels and assessed their correlation with HCC development in ALC patients. Results Serum myostatin levels were significantly higher in patients with HCC compared to those without (p &amp;lt; 0.001). Our analysis revealed a significant correlation between baseline myostatin levels and various clinical parameters, including gender (p &amp;lt; 0.0001), serum albumin (p &amp;lt; 0.0001), prothrombin time (PT) (p = 0.0188), serum ammonia (p &amp;lt; 0.002), and Child Pugh score (p &amp;lt; 0.0001). Multivariate Cox analyses identified age, gender, body mass index (BMI), platelet counts, and serum myostatin levels as independent risk factors for HCC development (p &amp;lt; 0.001). Conclusion Elevated serum myostatin levels are associated with an increased risk of HCC development in ALC patients. Myostatin may play a role in hepatic fibrogenesis and carcinogenesis, making it a potential prognostic marker for HCC in this population. A serum myostatin level cutoff of 3.9 ng/ml exhibited high sensitivity (92.3%) and specificity (82.35%) for detecting HCC. These findings suggest that serum myostatin levels could serve as a valuable tool for identifying high-risk ALC patients who may benefit from closer monitoring for HCC development.

Role of Serum Alpha-1-Acid Glycoprotein as a New Biomarker for Cirrhotic and Hepatocellular Carcinoma Patients

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it is the second leading cause of malignancy related mortality all over the world and is primarily due to the hepatitis C virus (HCV) epidemic. Aim of the Work to evaluate the diagnostic value of serum AAG level as a novel biomarker for HCC and cirrhotic patients Patients and Methods This study was conducted on ninety cases chosen from El Demerdash hospital (Ain Shams University) divided into three groups group (A) ten normal control people, group (B) forty known HCC patients which was further subdivided into two small subgroups B (I) twenty with low AFP level and B (II) twenty with high AFP level, as well as forty patients with liver cirrhosis group (C) during the period from June 2022 to December 2022. Results The mean value of AAG in HCC low AFP cases was 1307 μg/ml which was higher than that of patients with HCC high AFP (850 μg/ml) and chronic liver disease patients (309 μg/ml). AAG as a diagnostic marker for HCC the cut-off value was 740 ng/ml with sensitivity 73% and specificity 74% for HCC low AFP, which was higher than that of patients with HCC high AFP sensitivity 68% and specificity 71%. Conclusion Alpha 1 Acid Glycoprotein had better performance in diagnosing HCC patients with low AFP. Serum Alpha 1 Acid Glycoprotein (AAG) concentrations can used as a potential marker for hepatocellular carcinoma.

Evaluation the Role of Serum Epidermal Growth Factor Like Domain 7 as a New Non-Invasive Diagnostic Marker for Hepatocellular Carcinoma in Egyptian Cirrhotic Patients

Abstract Background Hepatocellular carcinoma (HCC) is a significant global health concern, ranking as the sixth most common cancer worldwide. In Egypt, it is the fourth most prevalent malignancy. The rising incidence of HCC has been attributed to advancements in screening programs, improved diagnostic tools, increased survival rates in cirrhotic patients, and a higher prevalence of hepatitis C virus (HCV) infections. Objective Point this study is to assess job serum epidermal development factor like space 7 as a demonstrative marker in HCC Egyptian cirrhotic patients. Methods A total of 90 subjects were enrolled in this study, categorized into two groups: Group A (HCC), comprising 45 patients with Hepatocellular carcinoma, and Group B (Cirrhotic), comprising 45 patients with liver cirrhosis without HCC. The study subjects underwent history taking, physical examination, routine laboratory tests, measurement of AFP and EGFL7 levels, and radiological evaluations. Results EGFL7, a molecule with signaling and EGF-like domains, was significantly upregulated in HCC tissues compared to cirrhotic tissues. High EGFL7 expression was associated with adverse clinicopathological features and poor prognosis in HCC patients. The study demonstrated that EGFL7 exhibited higher diagnostic performance in distinguishing between cirrhosis and HCC compared to AFP. Moreover, EGFL7 levels were positively correlated with the Child-Pugh score and the size of hepatic lesions in the HCC group. Conclusion This research highlights that serum EGFL7 is substantially elevated in HCC patients, particularly those with co-existing conditions such as diabetes, hypertension, or viral markers. EGFL7 emerges as a more sensitive and accurate marker than AFP for early HCC detection. Incorporating EGFL7 into diagnostic algorithms could enhance the effectiveness of surveillance programs for early HCC detection, ultimately leading to improved clinical outcomes and patient management.