Marker For Hepatocellular Carcinoma Research Articles

The Value of Serum MidKine as a Marker of Hepatocellular Carcinoma on Top of Hepatitis C Virus Related Cirrhosis

Background: Hepatocellular carcinoma (HCC) is characterized by the deficiency of specific symptoms in the early stages of the disease and a poor prognosis. Biomarkers that have the diagnostic ability to distinguish between inflammation, cirrhosis, and HCC are needed for early case detection. MidKine (MK) is overexpressed in many malignancies, including hepatocellular carcinoma, gastric carcinoma, colon carcinoma, lung carcinoma, urinary bladder carcinoma and prostate carcinoma. Objective: The objective is to evaluate serum MidKine as a marker of HCC in HCV-related liver cirrhosis. Patients and Methods: This study included 50 patients with HCC (on top of hepatitis C virus-related cirrhosis), 20 cirrhotic patients due to chronic HCV infection, and 10 normal subjects as a control group. History, examination, and laboratory investigations were performed on all subjects in the three groups including MK and Alpha fetoprotein (AFP) serum levels. Results: Serum levels of AFP and MK were higher in the HCC group than in the other study groups (P < 0.001). AFP was positive in 35 (70%) and negative in 15 (30%) whereas MK was positive in all HCC cases. There was a statistically significant correlation between MK serum levels and AFP serum levels, tumor size, and tumor stage. Conclusion: MidKine is a novel sensitive biomarker that could be used for early detection of HCC and has a high significance in differentiation between cirrhosis and HCC cases. MidKine levels are correlated with HCC stages and sizes.

External Validation of LCR1-LCR2, a Multivariable Hepatocellular Carcinoma Risk Calculator, in a Multiethnic Cohort of Patients With Chronic Hepatitis B.

The liver cancer risk test (LCR1-LCR2) is a multianalyte blood test combining proteins involved in liver cell repair (apolipoprotein A1, haptoglobin), hepatocellular carcinoma (HCC) risk factors (gender, age, gamma glutamyl transpeptidase), a marker of fibrosis (alpha2-macroglobulin), and alpha-fetoprotein, a specific marker of HCC. The aim was to externally validate LCR1-LCR2 in hepatitis B. Preincluded patients were from the Hepather cohort, a multicenter, multiethnic prospective study in 6071 patients. The coprimary study outcome was the negative predictive value of LCR1-LCR2 at 5 years for the occurrence of HCC and survival without HCC according to the predetermined LCR1-LCR2 cutoffs, adjusted for risk covariables and for chronic hepatitis B treatment and quantified using time-dependent Cox proportional hazards models. A post hoc analysis compared the number of patients needed to screen one cancer by LCR1-LCR2 and PAGE-B. A total of 3520 patients, 191 (5.4%) with cirrhosis, with at least 1 year of follow-up were included. A total of 76 HCCs occurred over a median (interquartile range) of 6.0 years (4.8-7.3) of follow-up. Among the 3367 patients with low-risk LCR1-LCR2, the 5-year negative predictive value was 99.3% (95% confidence interval= 99.0-99.6), with a significant Cox hazard ratio (6.4, 3.1-13.0; P < .001) obtained after adjustment for exposure to antivirals, age, gender, geographical origin, HBe-Ag status, alcohol consumption, and type-2 diabetes. LCR1-LCR2 outperformed PAGE-B for number of patients needed to screen mean (95% CI), 8.5 (3.2-8.1) vs 26.3 (17.5-38.5; P < .0001), respectively. The performance of LCR1-LCR2 to identify patients with chronic hepatitis B at very low risk of HCC at 5 years was externally validated. ClinicalTrials.gov: NCT01953458.

Immune-related DNA methylation signature associated with APLN expression predicts prognostic of hepatocellular carcinoma

This study used transcriptome and epigenetic data to predict the prognosis of immune-related genes (IRGs) Apelin (APLN) in patients with hepatocellular carcinoma (HCC). The TCGA database has gene expression and clinical data for HCC. And DNA methylation 450 k data for HCC was download from the University of California Santa Cruz (UCSC) Xena browser. Performing clinical and prognostic analysis of APLN expression, results show that APLN is highly expressed in tumor samples. And it has an increasing trend with the development of clinical stage and T stage. To explore the prognostic role of APLN, the Immune-related DNA methylation (DNAm) sites associated with APLN analyzed by bioinformatics. Univariate COX screened the methylation sites that are related to both APLN and survival. The risk score related to methylation site signature was determined according to their least absolute shrinkage and selection operator (LASSO) coefficients. Then the patients were divided into high-risk groups and low-risk groups. Significant differences in overall survival (OS) were found in the training cohort. Nomogram shows that APLN or methylation signature can effectively predict the prognosis of HCC patients. In summary, APLN may be a diagnostic and prognostic marker for HCC.

Study of hepatitis B core-related antigen as a predictor marker of hepatocellular carcinoma in patients with chronic hepatitis B

Background Cirrhosis and hepatocellular cancer are the most common complications of chronic hepatitis B and therefore it is necessary to avoid these complications in high-risk patients with high replicative capability. Conventional serum indicators are insufficient for detecting hepatocellular carcinoma in these patients early. Aim The goal of this study was to see if hepatitis B core-related antigen (HBcrAg) could be used as a marker for hepatocellular cancer in people who had hepatitis B. Patients and methods This research was conducted on 90 people who attended the Hepatitis Outpatient Clinics at the Department of Tropical Medicine and Tanta University Educational Hospital between January 2019 and August 2020. Results In comparison to the control group, hepatocellular carcinoma (HCC), and chronic hepatitis B (CHB) patients had a marked decline in hemoglobin, serum albumin, white blood cells count, and platelet count. Aspartate transaminase (AST), Alanine aminotansferase (ALT), bilirubin, and international normalization ratio (INR) levels all increased considerably. Hepatocellular carcinoma and CHB patients had relatively high levels of alkaline phosphatase (ALP) and Alpha-feto protien (AFP) than the control group. In both patient groups, there was a strong whereas ALT. Levels was within normal values. In the HCC group, HBcrAg levels were closely linked with ALP, AFP, and DNA levels. In both patient groups, the AST to Platelet Ratio Index (APRI) score indicated a strong association. Conclusion As an excellent biomarker of intrahepatic cccDNA, HBcrAg demonstrated encouraging results as a potential biomarker of HCC incidence in CHB patients.

Mac-2 Binding Protein Glycosylation Isomer as a Prognostic Marker for Hepatocellular Carcinoma With Sustained Virological Response.

Mac2-binding protein glycosylation isomer (M2BPGi) is a non-invasive marker for assessing liver fibrosis. This was a retrospective study investigating whether M2BPGi predicts recurrence of hepatocellular carcinoma (HCC) after hepatectomy in patients with HCC who achieved a sustained virological response (SVR). We retrospectively reviewed the clinicopathological factors from 60 patients who underwent hepatectomy for HCC after achieving a SVR. We divided all patients into high M2BPGi and low M2BPGi groups and analyzed the clinicopathological and surgical outcomes. High M2BPGi (>1.54, n=23) was significantly associated with lower serum albumin, higher ICGR15, higher Fib-4 index, large blood loss, and worse recurrence-free survival compared to low M2BPGi (≤1.54, n=37). Multivariate analysis identified high M2BPGi and large tumor size as being associated with reduced recurrence-free survival. Multivariate analysis identified lower serum albumin, larger tumor size and higher DCP as associated with reduced overall survival. There was no difference regarding recurrence pattern. Preoperative M2BPGi is a useful biomarker for HCC recurrence after hepatectomy for SVR-HCC.

Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma.

Methods MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. Results It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA (AUCMCM4 = 0.9461, AUCAFP = 0.7056) and GEO (GSE19665: AUCMCM4 = 0.8800, AUCAFP = 0.5100; GSE64041 AUCMCM4 = 0.8038, AUCAFP = 0.6304). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. Conclusion MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.

Large-Scale Tissue Microarray Evaluation Corroborates High Specificity of High-Level Arginase-1 Immunostaining for Hepatocellular Carcinoma.

Arginase-1 catalyzes the conversion of arginine to ornithine and urea. Because of its predominant expression in hepatocytes, it serves as a marker for hepatocellular carcinoma, although other tumor entities can also express arginase-1. To comprehensively determine arginase-1 expression in normal and neoplastic tissues, tissue microarrays containing 14,912 samples from 117 different tumor types and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, arginase-1 was expressed in the liver, the granular layer of the epidermis, and in granulocytes. Among tumors, a nuclear and cytoplasmic arginase-1 immunostaining was predominantly observed in hepatocellular carcinoma, where 96% of 49 cancers were at least moderately positive. Although 22 additional tumor categories showed occasional arginase immunostaining, strong staining was exceedingly rare in these entities. Staining of a few tumor cells was observed in squamous cell carcinomas of various sites. Staining typically involved maturing cells with the beginning of keratinization in these tumors and was significantly associated with a low grade in 635 squamous cell carcinomas of various sites (p = 0.003). Teratoma, urothelial carcinoma and pleomorphic adenomas sometimes also showed arginase expression in areas with squamous differentiation. In summary, arginase-1 immunohistochemistry is highly sensitive and specific for hepatocellular carcinoma if weak and focal staining is disregarded.

Single-Cell Sequencing of Hepatocellular Carcinoma Reveals Cell Interactions and Cell Heterogeneity in the Microenvironment.

BackgroundHepatocellular carcinoma (HCC) is the main histological subtype of liver cancer, which has the characteristics of poor prognosis and high fatality rate. Single-cell sequencing can provide quantitative and unbiased characterization of cell heterogeneity by analyzing the molecular profile of the whole genome of thousands of single cells. Thus, the purpose of this study was to identify novel prognostic markers for HCC based on single-cell sequencing data.MethodsSingle-cell sequencing of 21 HCC samples and 256 normal liver tissue samples in the GSE124395 dataset was collected from the Gene Expression Omnibus (GEO) database. The quality-controlled cells were grouped by unsupervised cluster analysis and identified the marker genes of each cell cluster. Hereafter, these cell clusters were annotated by singleR and CellMarker according to the expression patterns of the marker genes. Pseudotime analysis was performed to construct the trajectory of cell evolution and to define hub genes in the evolution process. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to explore the potential regulatory mechanism of hub genes in HCC. Next, the differential expression of hub genes and the correlation of the expression of these genes with patients’ survival and diagnosis were investigated in The Cancer Genome Atlas (TCGA) database.ResultsA total of 9 clusters corresponding to 9 cell types, including NKT cells, hepatocytes, endothelial cells, Kupffer cells, EPCAM+ cells, cancer cells, plasma cells (B cells), immature B cells, and myofibroblasts were identified. We screened 63 key genes related to cell differentiation through trajectory analysis, which were enriched in the process of coagulation. Ultimately, we identified 10 survival-related hub genes in the TCGA database, namely ALDOB, APOC3, APOH, CYP2E1, CYP3A4, GC, HRG, LINC01554, PDK4, and TXN.ConclusionIn conclusion, ALDOB, APOC3, APOH, CYP2E1, CYP3A4, GC, HRG, LINC01554, PDK4, and TXN may serve as hub genes in the diagnosis and prognosis for HCC.

Identification of molecular subtypes and prognostic signature for hepatocellular carcinoma based on genes associated with homologous recombination deficiency

Hepatocellular carcinoma (HCC) is a rapidly developing digestive tract carcinoma. The prognosis of patients and side effects caused by clinical treatment should be better improved. Nonnegative matrix factorization (NMF) clustering was performed using 109 homologous recombination deficiency (HRD)-related of HCC genes from The Cancer Genome Atlas (TCGA) database. Limma was applied to analyze subtype differences. Immune scores and clinical characteristics of different subtypes were compared. An HRD signature were built with least absolute shrinkage operator (LASSO) and multivariate Cox analysis. Performance of the signature system was then assessed by Kaplan–Meier curves and receiver operating characteristic (ROC) curves. We identified two molecular subtypes (C1 and C2), with C2 showing a significantly better prognosis than C1. C1 contained 3623 differentially expressed genes. A 4-gene prognostic signature for HCC was established, and showed a high predicting accuracy in validation sets, entire TCGA data set, HCCDB18 and GSE14520 queues. Moreover, the risk score was validated as an independent prognostic marker for HCC. Our research identified two molecular subtypes of HCC, and proposed a novel scoring system for evaluating the prognosis of HCC in clinical practice.

Liquid–Liquid Phase Separation-Related Genes Associated with Tumor Grade and Prognosis in Hepatocellular Carcinoma: A Bioinformatic Study

AimThe aim of the present study was to identify the association between tumor grade and liquid–liquid phase separation (LLPS)-related genes, and to generate a LLPS-related gene-based risk index (LLPSRI) as a prognostic tool for hepatocellular carcinoma (HCC).MethodsWeighted gene correlation network analysis was performed to test whether the LLPS-related gene modules were associated with tumor grade of HCC. The candidate modules were subjected to functional enrichment analysis. We generated a LLPSRI using the expression profiles of the hub genes among the candidate modules in order to identify patients at high risk. Then, the biological characteristics of the high-risk patients were revealed using gene set enrichment analysis. Additionally, an independent external data set was used to validate the LLPSRI.ResultsFour gene modules showed a significant positive correlation with tumor grade and involved various cancer-related pathways. Among the hub genes, six were selected to generate the LLPSRI, which was significantly associated with prognosis of HCC patients. The LLPSRI could successfully divide patients with HCC into high- and low-risk groups, and patients in the high-risk group showed shorter overall survival than those in the low-risk group. E2F, MYC, and mTORC1 signaling may be important determinants of survival in the high-risk group. The prognostic value of the LLPSRI was validated with the independent external data set.ConclusionWe identified LLPS-related gene modules that are associated with HCC tumor grade. The LLPSRI may be useful as a prognostic marker of HCC, and it may reliably stratify patients into groups at low or high risk of worse survival. Our analysis also suggests that certain biological characteristics of HCC may be associated with high risk of worse survival.

30P Differential expression of miR-873, miR-181a and miR-17-5p and their correlation with immune checkpoints PD-L1 and CD155 among hepatocellular carcinoma patients

By 2030, the world is expected to have 1 million Hepatocellular carcinoma (HCC)-related deaths annually. HCC is asymptomatic in early stages, a matter that negatively affect its timely diagnosis. Nonetheless, the lack of prognostic markers for HCC is another vital parameter that worsens the scenario. MicroRNAs are considered as stable, easily detectable, non-invasive biomarkers. miR-873, miR-181a and miR-17-5p are paradoxically acting miRNAs in several malignancies. Yet, their expression patterns in HCV-induced HCC patients are still to be explored.

High expression of MRPL52 can be used as a prognostic marker of hepatocellular carcinoma and is related to immune infiltration

ObjectiveTo analyze the differential expression and prognostic value of Mitochondrial ribosomal protein L52 (MRPL52) in hepatocellular carcinoma using bioinformatics, and to explore the prognostic value and role of the MRPL52 in the immune regulation of hepatocellular carcinoma. MethodsHepatocellular Carcinoma Database (HCCDB) and Tumor Immune Estimation Resource (TIMER) databases were used in analyzing the differential expression of MRPL52 in hepatocellular carcinoma tissue and normal paracancerous tissues; UALCAN database was used to analyze the correlation between levels of MRPL52 expression and levels of DNA methylation vs. clinical phenotypes, including tumor grade, tumor stage, and metastasis, Kaplan–Meier plotter database was used in analyzing the relationship between MRPL52 expression and hepatocellular carcinoma survival; LinkedOmics database was used in analyzing MRPL52 co-expression genes, target miRNAs and transcription factors; GENEMANIA database was used to construct the protein interaction network; DiseaseMeth database and MEXPRESS database were used to analyze the level of MRPL52 DNA methylation and changes in methylation sites, and TIMER database was used in analyzing the relationship between MRPL52 and immune infiltration of hepatocellular carcinoma. ResultsMRPL52 was highly expressed in hepatocellular carcinoma and was positively correlated with clinical phenotypes, including tumor grade, tumor stage, and distant metastasis; high expression of MRPL52 was associated with poor prognosis of hepatocellular carcinoma; co-expression analysis showed that MRPL52 co-expression genes were enriched in multiple cancer-related signal pathways, and methylation analysis showed that the DNA methylation level of MRPL52 reduced significantly in hepatocellular carcinoma. Additionally, significant changes were found in methylation sites cg07436208 and cg04556361, which were negatively correlated with the expression level of MRPL52, and K–M survival analysis showed that the cg04556361 methylation site was negatively correlated with the overall survival of hepatocellular carcinoma; MRPL52 was associated with immune cell infiltration of hepatocellular carcinoma, and Cox multivariate regression analysis showed that MRPL52 could increase the risk of overall survival (OS) by 1.435-fold in the absence of immune cells. ConclusionThe expression level of MRPL52 in patients with hepatocellular carcinoma is increased, which is related closely to poor prognosis, suggesting that MRPL52 is expected to become a prognostic marker and a new target for the treatment of hepatocellular carcinoma.

LINC00839/miR-144-3p/WTAP (WT1 Associated protein) axis is involved in regulating hepatocellular carcinoma progression

ABSTRACT The present work aimed to explore LINC00839 expression level and its function in hepatocellular carcinoma (HCC), and identify the downstream molecular mechanisms. qRT-PCR (Real-Time Quantitative Reverse Transcription PCR) and western blot were employed to detect mRNA and protein levels. Functional investigations were performed by flow cytometric-based apoptosis assay, CCK8 (Cell Counting Kit-8) assay, clone formation assay, Transwell migration and invasion assay. Functional interactions between LINC00839 and miR-144-3p or miR-144-3p and WTAP were validated by dual luciferase reporter assay. siRNA (small interfering RNA) was used for LINC00839 silencing, and microRNA mimic or inhibitor were employed to modulate miR-144-3p activity. LINC00839 was upregulated in HCC cells and tissues. Silencing LINC00839 suppressed the proliferation, invasion, migration of HCC cells and induced apoptosis. Additionally, LINC00839 served as a sponge to negatively impact on miR-144-3p activity, which contributed to the high expression of WTAP (WT1 Associated Protein) and the malignant phenotype of HCC cells. Our study revealed an oncogenic role of LINC00839 in HCC, and identified miR-144-3p/WTAP axis as downstream effectors mediating the oncogenic function of LINC00839. LINC00839 might serve as a potential therapeutic target and prognostic marker for HCC.

Circulating MicroRNA-21 As A Novel Noninvasive Biomarker for Hepatocellular Carcinoma Compared with Alpha Fetoprotein Gold Test

Hepatocellular carcinoma (HCC) is the greatest traditional kind of pre-eminent cancer worldwide, which happens mainly in chronic liver disease and cirrhotic patients. The available surveillance strategies for suspected HCC patients include serum alpha-fetoprotein (AFP) and liver imaging have been mainly recommended. However, the sensitivity and selectivity of these diagnostic strategies especially in the early stages of HCC have many obstacles. MicroRNAs (miRNAs) are non-coding RNAs that are 18–25 nucleotides in length. Plasma miRNAs may be a promising new biomarker for cancer detection and prognosis in the early stages. Assessment of Plasma MicroRNA-21 (miRNA-21) significance as a noninvasive Hepatocellular carcinoma marker compared with AFP gold standard test to improve HCC early diagnostic power. This is a prospective research project that included 90 patients in total, split into three classes., liver cirrhosis patients (LC) without any malignancies and (HCC) patients in addition to the healthy control group. Patients and controls were subjected to the clinical studies, routine investigations, imaging studies, and detection of plasma miRNA-21 &amp; AFP. miRNA-21 showed a highly significant difference in the 3 studied groups. Control group with LC group, control group with HCC group, and LC group with HCC group P value (P 0.0001, P1 0.0001, P2 0.0001and P3 0.0001) respectively. Also, a highly significant difference was observed between pre-TACE and post-TACE miRNA-21 in the HCC group P value (0.0001). Circulating miRNA-21 may be used as a noninvasive co biomarker with AFP to increase HCC diagnostic accuracy in its early stages.

Mitochondrial transcription factor B1 promotes the progression of hepatocellular carcinoma via enhancing aerobic glycolysis.

Mitochondrial dysfunctions play crucial roles in the carcinogenesis of various human cancers. However, the molecular mechanisms leading to mitochondrial dysfunction and thus cancer progression remains largely unclear. TFB1M (mitochondrial transcription factor B1) is a mitochondrial DNA-binding protein that activates the transcription of mitochondrial DNA. Our bioinformatics analysis indicated a significant up-regulation of TFB1M in hepatocellular carcinoma (HCC). Here, we investigated its clinical significance and biological functions in this malignancy. Here, we found that TFB1M was significantly upregulated in HCC cells probably due to decreased miR-130a-3p expression. High TFB1M expression was positively associated with poor patient survival in HCC. TFB1M contributes to HCC growth and metastasis by promoting cell cycle progression, epithelia-mesenchymal transition (EMT), and inhibiting cell apoptosis. Mechanistically, the metabolic switch from oxidative phosphorylation to glycolysis contributed to the promotion of tumor growth and metastasis by TFB1M overexpression in HCC cells. In summary, we demonstrate that TFB1M plays a crucial oncogenic role in HCC progression, indicating TFB1M as a promising prognostic marker and therapeutic target in HCC.

Inositol 1,4,5-trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma.

The expression of the inositol 1,4,5-trisphosphate receptor type 3 (ITRP3) in hepatocytes is a common event in the pathogenesis of hepatocellular carcinoma (HCC), regardless of the type of underlying liver disease. However, it is not known whether ITPR3 expression in hepatocytes is involved in tumor maintenance. The aim of the present study was to determine whether there is an association between ITPR3 expression and clinical and morphological parameters using HCC samples obtained from liver explants from patients (n=53) with different etiologies of underlying chronic liver disease (CLD). ITPR3 expression, mitosis and apoptosis were analyzed in human liver samples by immunohistochemistry. Clinical and event-free survival data were combined to assess the relationship between ITPR3 and liver cancer growth in patients. RNA sequencing analysis was performed to identify apoptotic genes altered by ITPR3 expression in a liver tumor cell line. ITPR3 was highly expressed in HCC tumor cells relative to adjacent CLD tissue and healthy livers. There was an inverse correlation between ITPR3 expression and mitotic and apoptotic indices in HCC, suggesting that ITPR3 contributed to the maintenance of HCC by promoting resistance to apoptosis. This was confirmed by the upregulation of CTSB, CHOP and GADD45, genes involved in the apoptotic pathway in HCC. The expression of ITPR3 in the liver may be a promising prognostic marker of HCC

VEGF Family Gene Expression as Prognostic Biomarkers for Alzheimer's Disease and Primary Liver Cancer.

Background To analyze the expression of vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) and cognitive impairment, explore the relationship between the expression of VEGF family genes and prognosis of patients with HCC, and evaluate the predictive ability of VEGF in cognitive impairment using computerized methods. Methods VEGF expression in liver cancer tissues and normal tissues was analyzed using bioinformatics methods. The Kaplan-Meier survival analysis method was also used to analyze the relationship between VEGF expression and the prognosis of patients with HCC. Furthermore, immune infiltration assessment and gene set enrichment analysis were performed. Meanwhile, the differential expression of VEGF family genes between patients with Alzheimer's disease (AD) and healthy controls was also checked. Results Based on The Cancer Genome Atlas (TCGA) database, the VEGF family genes (VEFGA, VEGFB, VEGFC, and VEGFD) were highly expressed in cancer tissues and were significantly associated with poor prognosis in HCC. In HCC, the VEGF family genes showed significant heterogeneity in their functional and immune infiltration characteristics. Finally, VEGF family genes were identified as prognostic biomarkers in AD and risk prediction markers in HCC. Conclusions VEGF is highly expressed in patients with HCC and lowly expressed in patients with AD. VEGF has opposite opposing roles in the treatment of tumors and cognitive impairment.

Diagnostic value of RNA for hepatocellular carcinoma: a network meta-analysis.

Aim: The aim of this study was to evaluate the capacity of RNA in the diagnosis of hepatocellular carcinoma (HCC). Methods: A systematic review was conducted from PubMed, Cochrane Library, EMBASE and Web of Science databases via well-designed retrieval strategy. Subsequently, the network meta-analysis was performed by the STATA software. Results: Through statistical analysis, the three hypotheses of the network meta-analysis were established. In view of these hypotheses, the diagnostic efficacy of the three markers in HCC (HCC vs healthy people) may be consistent, and the cumulative ranking results showed such a trend: circular RNA >long noncoding RNA >microRNA. Conclusion: Circular RNA may be most effective for diagnosing HCC across the three types of RNA.

M6A-Mediated Upregulation of LINC00106 Promotes Stemness and Metastasis Properties of Hepatocellular Carcinoma via Sponging Let7f.

Background: Hepatocellular carcinoma (HCC) cells exhibit the stemness property, which makes the patient with HCC prone to tumor recurrence and metastasis. Despite the prominent regulatory role of long non-coding RNAs (lncRNAs) in tumor stemness, the roles and molecular mechanisms of LINC00106 in HCC are poorly understood. Methods: LINC00106, let7f and periostin expression levels in tissue specimens and cell lines were assessed through qRT-PCR and immunohistochemistry (IHC). Various in vivo and in vitro assays, namely sphere/colony formation, proportion of side population cells (SP%), invasion, migration, western blot, and murine xenograft model were employed for assessing the stemness and metastatic properties of HCC cells. Luciferase reporter assays, RNA-seq, RNA pull-down, RNA immunoprecipitation (RIP) were conducted to clarificate the target gene and analyze the underlying mechanisms. Results: LINC00106 was prominently upregulated in tissues and cell lines of HCC. Patients having a high LINC00106 level exhibited a poor outcome. Under in vivo and in vitro conditions, the stemness and metastatic properties of HCC cells were augmented by LINC00106. Additionally, LINC00106 was found to sponge let7f to upregulate periostin, which lead to the activation of periostin-associated PI3K-AKT signaling pathway. Moreover, m6A methylation was found to cause LINC00106 upregulation while maintaining LINC00106 RNA transcript stability. Conclusion: m6A methylation triggers the upregulation of LINC00106, which promotes the stemness and metastasis properties in HCC cells by sponging let7f, thereby resulting in periostin activation. The findings indicate the potential of LINC00106 as a diagnostic marker and therapeutic target for HCC.

A novel model based on interleukin 6 and insulin-like growth factor II for detection of hepatocellular carcinoma associated with hepatitis C virus

BackgroundThe coexistence of cirrhosis complicates the early detection of hepatocellular carcinoma (HCC). Thus, novel biomarkers for HCC early detection are needed urgently. Traditionally, HCC detection is carried out by evaluating alpha-fetoprotein (AFP) levels combined with imaging techniques. This work aimed to assess interleukin (IL-6) and insulin-like growth factor 2 (IGF 2) as possible HCC markers in comparison to AFP in patients with and without HCC. ResultsROC analysis showed that IGF2 had the highest area under the curve (AUC) for discriminating HCC from liver cirrhosis (0.86), followed by IL6 (0.82), AFP (0.72), and platelet count (0.6). A four-marker model was developed and discriminated HCC from liver cirrhosis with an AUC of 0.97. The best cut-off was 1.28, at which sensitivity and specificity were 90% and 85%, respectively. For small tumor (< 2 cm), the model had an AUC of 0.95 compared to AFP (0.72). Also, the model achieved perfect performance with AUC of 0.93, 0.94, and 0.95 for BCLC (0-A), CLIP (0-1), and Okuda (stage I), respectively, compared to AFP (AUC of 0.71, 0.69, and 0.67, respectively). ConclusionsThe four markers may serve as a diagnostic model for HCC early stages and help overcome AFP poor sensitivity.