Diagnostic Value For Hepatocellular Carcinoma Research Articles

Computed tomography-based radiomics predicts the fibroblast-related gene EZH2 expression level and survival of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer. The primary treatment strategies for HCC currently include liver transplantation and surgical resection. However, these methods often yield unsatisfactory outcomes, leading to a poor prognosis for many patients. This underscores the urgent need to identify and evaluate novel therapeutic targets that can improve the prognosis and survival rate of HCC patients. AIM To construct a radiomics model that can accurately predict the EZH2 expression in HCC. METHODS Gene expression, clinical parameters, HCC-related radiomics, and fibroblast-related genes were acquired from public databases. A gene model was developed, and its clinical efficacy was assessed statistically. Drug sensitivity analysis was conducted with identified hub genes. Radiomics features were extracted and machine learning algorithms were employed to generate a radiomics model related to the hub genes. A nomogram was used to illustrate the prognostic significance of the computed Radscore and the hub genes in the context of HCC patient outcomes. RESULTS EZH2 and NRAS were independent predictors for prognosis of HCC and were utilized to construct a predictive gene model. This model demonstrated robust performance in diagnosing HCC and predicted an unfavorable prognosis. A negative correlation was observed between EZH2 expression and drug sensitivity. Elevated EZH2 expression was linked to poorer prognosis, and its diagnostic value in HCC surpassed that of the risk model. A radiomics model, developed using a logistic algorithm, also showed superior efficiency in predicting EZH2 expression. The Radscore was higher in the group with high EZH2 expression. A nomogram was constructed to visually demonstrate the significant roles of the radiomics model and EZH2 expression in predicting the overall survival of HCC patients. CONCLUSION EZH2 plays significant roles in diagnosing HCC and therapeutic efficacy. A radiomics model, developed using a logistic algorithm, efficiently predicted EZH2 expression and exhibited strong correlation with HCC prognosis.

KLF15-activated MARCH2 boosts cell proliferation and epithelial-mesenchymal transition and presents diagnostic significance for hepatocellular carcinoma

PurposeMembrane associated ubiquitin ligase MARCH2 majorly involves in inflammation response and protein trafficking. However, its comprehensive role in hepatocellular carcinoma (HCC) is largely unknown. MethodsFirstly, multiple bioinformatic analyses were applied to determine MARCH2 mRNA level, its expression comparison in diverse molecular and immune subtypes, and diagnostic value in HCC. Subsequently, RNA-seq, real-time quantitative PCR, immunohistochemistry and cell proliferation assay are used to explore the epithelial–mesenchymal transition (EMT) and proliferation by gene-silencing or overexpressing in cultured HCC cells or in vivo xenograft. Moreover, dual luciferase reporter assay and immunoblotting are delved into verify the transcription factor that activating MARCH2 promoter. ResultsMultiple bioinformatic analyses demonstrate that MARCH2 is upregulated in multiple cancer types and exhibits startling diagnostic value as well as distinct molecular and immune subtypes in HCC. RNA-seq analysis reveals MARCH2 may promote EMT, cell proliferation and migration in HepG2 cells. Furthermore, overexpression of MARCH2 triggers EMT and significantly enhances HCC cell migration, proliferation and colony formation in a ligase activity-dependent manner. Additionally, above observations are validated in the HepG2 mice xenografts. For up-stream mechanism, transcription factor KLF15 is highly expressed in HCC and activates MARCH2 expression. ConclusionKLF15 activated MARCH2 triggers EMT and serves as a fascinating biomarker for precise diagnosis of HCC. Consequently, MARCH2 emerges as a promising candidate for target therapy in cancer management.

The Diagnostic Value of Alpha-fetoprotein and Lens Culinaris Agglutinin-reactive Alpha-fetoprotein in Liver Cirrhosis and Hepatocellular Carcinoma patients in Pakistan

Background: Hepatocellular carcinoma (HCC) is the most commonly encountered liver cancer and it accounts for 7% of all cancers and is accountable for a million deaths yearly.
 Because of latent HCV infections in our general population, there is projected rise in new HCC cases in Pakistan; with the onset of HCC several decades after initial infection has occurred. The poor predicted outcome of HCC is because of the fact that in the disease course of HCC, it is diagnosed at a very late stage. This results in effective medical intervention difficult.
 The purpose of this study is to establish a serum marker and/or panels of serum markers, that can detect the at risk patients with chronic liver disease, not only before but also after early development of HCC.
 Methodology: This study was conducted for ten months in Lahore General Hospital, Lahore, Punjab, Pakistan after taking the approval from the ethical board. A total of eighty patients (40 patients of HCC and 40 patients of LC) were included using non-probability, consecutive sampling. AFP and AFP-L3 levels of these patients were measured. The data was analyzed using SPSS Ver. 25. A p-value of ≤0.05 was considered as statistically significant.
 Results: In group 1, the mean age of patients was 60.02 ± 11.5 years and in group 2, it was 60.80 ± 7.42 years. In group 1, the mean of AFP was 64.93 ± 171.76 (ng/mL) and AFP-L3 was 0.56 ± 0.51(ng/mL). On the other hand, in group 2, the mean of AFP was 329.88 ± 231.55 (ng/mL) and AFP-L3 was 177.59 ± 104.10 (ng/mL). Significant association was found between AFP and AFP-L3 in both groups. Receiver operating characteristic (ROC) curve for AFP and AFP-L3 in relation to both groups obtained. The sensitivity of AFP was 85% and specificity was 80%. The sensitivity and specificity of AFP-L3 was 90 and 100%, respectively.
 Conclusion: AFP-L3 has a better diagnostic value for hepatocellular carcinoma than AFP.

Potential functions and causal associations of VPS29 in hepatocellular carcinoma: a bioinformatic and Mendelian randomization study.

Vacuolar protein sorting-associated protein 29 (VPS29) plays a certain role in cancer, but its biological significance in hepatocellular carcinoma (HCC) has not been studied. We utilized bioinformatics and Mendelian randomization (MR) analysis to explore the potential function of the VPS29 gene in HCC, as well as the causal relationship between VPS29 protein and HCC. We downloaded the raw data from TCGA, GEO, and IEU OpenGWAS databases. We used R software for data processing and analysis to explore the relationship between the VPS29 gene and the expression, prognosis, clinical features, methylation, immune microenvironment, tumor mutation burden, and drug sensitivity in HCC patients. Additionally, a two-sample Mendelian randomization analysis was conducted to investigate the causal relationship between the VPS29 protein and HCC. VPS29 was found to be overexpressed in various types of cancer, including HCC, and its elevated expression often predicts poor prognosis in HCC patients. Univariate and multivariate Cox analysis demonstrated that VPS29 was an independent prognostic factor in HCC patients. The ROC curve indicated that VPS29 has a high diagnostic value in HCC. There were differential expressions of VPS29 in various clinical feature subgroups. The expression of VPS29 was negatively correlated with methylation levels, and multiple methylation sites were identified in the promoter region, including cg20877181, cg03867797, cg10025392, cg21605021, which were associated with poorer overall survival (OS) at low methylation levels. VPS29 was associated with immune cell infiltration disorders, including CD8+ T cells, Eosinophils, Neutrophils, Tcm, NK CD56bright cells, TFH, Th2 cells, Th17 cells, etc. Drug sensitivity analysis showed that VPS29 could be indicative of treatment response to 10 common antineoplastic drugs in different expression subgroups. Inverse variance weighted (IVW) analysis revealed a significant increase in HCC risk associated with VPS29 [odds ratio (OR): 1.440; 95% confidence interval (CI): 1.195-1.736], and sensitivity analysis showed no heterogeneity or pleiotropy. VPS29 is a risk factor for the occurrence and progression of HCC and may serve as a molecular biomarker for the diagnosis and prognosis of HCC.

Human Proteome Microarray identifies autoantibodies to tumor-associated antigens as serological biomarkers for the diagnosis of hepatocellular carcinoma.

The identification of the high-efficiency and non-invasive biomarkers for hepatocellular carcinoma (HCC) detection is urgently needed. This study aims to screen out potential autoantibodies to tumor-associated antigens (TAAbs) and to assess their diagnostic value for HCC. Fifteen potential TAAbs were screened out from the Human Proteome Microarray by 30 HCC sera and 22 normal control sera, of which eight passed multiple-stage validations by ELISA with a total of 1625 human serum samples from normal controls (NCs) and patients with HCC, liver cirrhosis, chronic hepatitis B, gastric cancer, esophageal cancer, and colorectal cancer. Finally, an immunodiagnostic model including six TAAbs (RAD23A, CAST, RUNX1T1, PAIP1, SARS, PRKCZ) was constructed by logistic regression, and yielded the area under curve (AUC) of 0.835 and 0.788 in training and validation sets, respectively. The serial serum samples from HCC model mice were tested to explore the change in TAAbs during HCC formation, and an increasing level of autoantibodies was observed. In conclusion, the panel of six TAAbs can provide potential value for HCC detection, and the strategy to identify novel serological biomarkers can also provide new clues in understanding immunodiagnostic biomarkers.

SLC17A2 Expression Correlates with Prognosis and Immune Infiltrates in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a dismal prognosis, according to updated statistics. The solute carrier family 17 member 2 (SLC17A2) has not been studied in liver cancer. Therefore, we evaluated the role of SLC17A2 in HCC by bioinformatics analysis. The objective of the study was to explore the value of SLC17A2 in the prognosis and diagnosis of hepatocellular carcinoma. The expression level of SLC17A2 in HCC and the clinicopathological data were analyzed based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and validated by immunohistochemical staining. In addition, the Kaplan-Meier plotter database and receiver operating characteristic (ROC) curve analysis were used to explore the prognostic and diagnostic significance. Some online databases were used to analyze the relationship between immune cell infiltration and analyze the relationship between immune cell infiltration and SLC17A2 in HCC. Multivariate Cox regression analysis showed that SLC17A2 expression was low in HCC (P < 0.05) and closely related to the clinical stage of HCC. In addition, SLC17A2 had a certain diagnostic value in HCC according to ROC curve analysis. Further biological analyses showed that SLC17A2 can regulate fatty acid metabolism, amino acid metabolism and cytochrome P450- related metabolism. Notably, we found that SLC17A2 expression was closely correlated with the infiltration of most immune cells in HCC. SLC17A2 expression is low in HCC and correlates with immune infiltration, so it may serve as an independent prognostic factor for HCC.

Identification of a Two-lncRNA Signature with Prognostic and Diagnostic Value for Hepatocellular Carcinoma.

Background Accumulating evidence has revealed the important role of long noncoding RNAs (lncRNA) in tumorigenesis and progression of hepatocellular carcinoma (HCC). This study aimed to identify potential lncRNAs that can serve as diagnostic and prognostic signatures for HCC. Methods Expression profiling analysis was performed to identify differentially expressed lncRNAs (DElncRNA) between HCC and matched normal samples by integrating two independent microarray datasets. Functional Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were explored by Gene Set Variation Analysis. The prognostic and diagnostic models were developed based on two DElncRNAs. Real-time PCR was used to quantify the relative expressions of candidate lncRNAs. Results Two robust DElncRNAs were identified and verified by quantitative PCR between HCC and matched normal samples. Function enrichment analysis revealed that they were associated with the wound healing process. The two lncRNAs were subsequently used to construct a prognostic risk model for HCC. Patients with high-risk scores estimated by the model showed a shorter survival time than low-risk patients (P < 0.001). Besides, the two lncRNA-based HCC diagnostic models exhibited good performance in discriminating HCC from normal samples on both training and test sets. The values of area under the curve (AUC) for early (I–II) and late (III–IV) HCC detection were 0.88 and 0.93, respectively. Conclusions The two wound healing-related DElncRNAs showed robust performance for HCC prognostic prediction and detection, implying their potential role as diagnostic and prognostic markers for HCC.

Early Diagnosis Value of DCE-MRI Hemodynamic Parameters in Hepatocellular Carcinoma.

Objective To probe into the early diagnosis value of transfer coefficient (Ktrans) and rate constant (Kep) of the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) hemodynamic parameters in patients with hepatocellular carcinoma (HCC). Methods Fifty patients with HCC diagnosed in our hospital from May 2017 to May 2020 were studied retrospectively as the patient group (PG), and 45 cases with benign liver nodules diagnosed in our hospital during the same period were collected as the control group (CG). Ktrans, Kep, and AFP levels were compared between PG and CG. The diagnostic value of Ktrans and Kep in HCC were observed, and their correlations with patient clinical data were analyzed. The diagnostic value of Ktrans and Kep combined with AFP in clinical staging, differentiation degree, and distant metastasis was compared. Results K trans, Kep, and AFP were notably higher in cases than in controls (P < 0.05), indicating their high diagnostic value in HCC. Ktrans and Kep present elevated expression in HCC patients with clinical stage III-IV, low differentiation, and distant metastasis (P < 0.05). Furthermore, it is found that the combined detection with either Ktrans or Kep can improve the clinical diagnostic value of AFP in the clinical stage and differentiation of HCC. However, the combined diagnosis showed little effect in raising the sensitivity of AFP in distant metastasis. Conclusion DCE-MRI hemodynamic parameters Ktrans and Kep have high clinical value in early diagnosis and differentiation of HCC patients.

A novel hypoxia-driven gene signature that can predict the prognosis of hepatocellular carcinoma

ABSTRACT Hypoxia environment exists in already started hepatocellular carcinoma (HCC) and promotes its progression by driving changes in the gene expression profiles of cells. However, the status of hypoxia-driven genes in HCC is largely unknown. In the present study, 368 HCC tissues from The Cancer Genome Atlas were divided into high and low hypoxia groups according to their hypoxia signatures. A total of 1,142 differentially expressed genes (DEGs) were identified between the two groups, and 34 of these DEGs were highly expressed in HCC tissues compared with adjacent tissues, especially in HCC tissues from patients with stage III–IV HCC. After constructing a protein–protein interaction network and applying the least absolute shrinkage and selection operator Cox regression method for 34 DEGs, a three-gene signature (complement factor H related 3 [CFHR3], egl-9 family hypoxia inducible factor 3 [EGLN3], and chromogranin A [CHGA]) was constructed and had prognostic value to predicted outcome of patients with HCC. This three-gene signature was suitable for classifying patients with HCC in the International Cancer Genome Consortium. CFHR3 shows remarkable diagnostic value in HCC. Hypoxia decreased CFHR3 expression, but increased HCC cell proliferation and motility. Overexpression of CFHR3 in HCC cells under hypoxia reversed the stimulatory effects of hypoxia and suppressed cell proliferation and metastasis in vivo. In conclusion, we identified a novel hypoxia-driven gene signature (CFHR3, EGLN3, and CHGA) for reliable prognostic prediction of HCC, and demonstrated that overexpression of CFHR3 may be a potential strategy to overcome hypoxia and treat HCC.

High Expression of Ubiquitin-Specific Protease 39 and Its Roles in Prognosis in Patients with Hepatocellular Carcinoma.

Background Ubiquitin-specific protease 39 is mainly involved in mRNA splicing and multiple kinds of tumors. Accumulating evidence has shown that USP39 participated in the proliferation and metastasis of hepatocellular carcinoma (HCC). The present study aimed to demonstrate the association between USP39 expression and clinical features and the diagnostic value in HCC based on the Cancer Genome Atlas (TCGA). Methods A comprehensive analysis for expression of USP39 in HCC was conducted by using multiple databases. The mRNA level of USP39, clinical features, survival rate, and diagnostic value in HCC were analyzed using data from TCGA. The Gene Set Enrichment Analysis (GSEA) was conducted to analyze signaling pathways correlated with USP39 expression in HCC. Results The mRNA level of USP39 was significantly elevated in HCC. The expression of USP39 showed significant correlation with T stage, pathologic stage, tumor status, age, and histologic grade. Logistic analysis demonstrated that high expression of USP39 was significantly associated with older age, tumor status, advanced pathologic stage, T stage, and higher histologic grade. Univariate Cox regression analysis showed that high expression of USP39 was significantly associated with advanced T stage, pathological stage, and tumor status. Multivariate Cox analysis confirmed the result that USP39 expression was an independent prognostic factor for overall survival (OS) in HCC. Results of Kaplan–Meier curves showed that high expression of USP39 had a significant association with poor OS, disease-free survival (DSS), and progress-free interval (PFI) in HCC. ROC analysis indicated that USP39 could be regarded as a promising marker for distinguishing HCC from nontumor. Conclusion The increased USP39 might play roles in the progression, diagnosis, and prognosis of HCC.

PRCC reduces the sensitivity of cancer cells to DNA damage by inhibiting JNK and ATM/ATR pathways and results in a poor prognosis in hepatocellular carcinoma

Background and aimThe proline rich mitotic checkpoint control factor (PRCC) is involved in the splicing process of pre-mRNA. This study aims to elucidate PRCC molecular function, regulatory mechanism and diagnostic value in hepatocellular carcinoma (HCC).MethodsThe tissue microarray and serum samples from HCC patients were used to investigate the clinical value of PRCC. The biological function and molecular mechanism of PRCC were demonstrated by cell biology, biochemical and animal experiments. The relationship between PRCC and intratumoral heterogeneity (ITH) was analyzed by bioinformatics.ResultsPRCC was highly expressed in HCC tissues and related to the poor prognosis of HCC patients, its contents were elevated in the preoperative sera of HCC patients. PRCC exhibited high application potential as a substitute or adjuvant of alpha-fetoprotein (AFP) for clinical diagnosis of HCC. It had no significant effect on the proliferation of cancer cells, but could inhibit spheroid formation and metastasis of HCC cells in vitro and in vivo. The high ectopic expression of PRCC made cancer cells insensitive to DNA damage, and enhanced the heterogeneity of HCC cells by inhibiting the JNK/ATM/ATR/ATF2 axis. The HCC patients with high PRCC expression had high ITH, which corresponded to a short overall survival in patients.ConclusionsPRCC has high application potential as a substitute or adjuvant of AFP for clinical diagnosis of HCC. The high ectopic expression of PRCC not only caused HCC cells to resist to cell death induced by DNA damage, but also endowed cancer cells with numerous DNA mutations to become increasingly heterogeneous, finally leading to a poor prognosis in HCC patients. These data suggested PRCC could be a promising therapeutic target in HCC patients.

RNA sequencing identifies two novel liver-specific long noncoding RNAs with potential diagnostic value in hepatocellular carcinoma.

Aim: To explore the expression profiles of long noncoding RNAs (lncRNAs) and identify novel lncRNAs as biomarkers for early diagnosis and therapy of hepatocellular carcinoma (HCC). Materials & methods: Expression profiles of lncRNAs and mRNAs in five paired HCC and adjacent normal tissues were obtained by RNA sequencing. Eight lncRNAs, including two novel liver-specific lncRNAs (NONHSAT059247.2 and NONHSAT013897.2), were validated in another 74 pairs of HCC and adjacent normal tissues by quantitative reverse transcription PCR. Results: The results of quantitative reverse transcription PCR showed that NONHSAT252133.1, NONHSAT112116.2 and NONHSAT242657.1 were significantly upregulated in HCC tissues, whereas NONHSAT169790.1, NONHSAT059247.2 and NONHSAT013897.2 were significantly downregulated. Two liver-specific lncRNAs demonstrated excellent diagnostic performance: NONHSAT059247.2 (area under the curve=0.941, 95% CI: 0.902-0.979, p < 0.0001), NONHSAT013897.2 (area under the curve=0.944, 95% CI: 0.906-0.983, p < 0.0001). Conclusion: The liver-specific lncRNAs NONHSAT059247.2 and NONHSAT013897.2, may provide new biomarkers for the future study on diagnosis, therapy and mechanisms of HCC.

The diagnostic and prognostic value of H2AFY in hepatocellular carcinoma

BackgroundThe potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed.MethodsThe gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY.ResultCompared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways.ConclusionOur study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.

Integrated Analysis of an lncRNA-Associated ceRNA Network Reveals Potential Biomarkers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide. In this study, we aimed to explore the potential biomarkers and key regulatory pathways related to HCC using integrated bioinformatic analysis and validation. The microarray data of GSE12717 and GSE54238 were downloaded from the Gene Expression Omnibus database. A competing endogenous RNA (ceRNA) network was constructed based on potential long-noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA interactions. A total of 191 mRNAs, 8 miRNAs, and 5 lncRNAs were selected to construct the ceRNA network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. The PI3K-Akt signaling pathway was significantly enriched. Kaplan-Meier survival analysis based on the Gene Expression Profiling Interactive Analysis (GEPIA) database was conducted for the weighted mRNAs and lncRNAs. The results showed that SRC, GMPS, CDK2, FEN1, EZH2, ZWINT, MTHFD1L, GINS2, and MAPKAPK5-AS1 were significantly upregulated in tumor tissues. The relative expression levels of these genes were significantly upregulated in HCC patients based on the StarBase database. For further validation, the expression levels of these genes were detected by real-time quantitative reverse transcription-polymerase chain reaction in 20 HCC tumor tissues and paired paracancerous tissues. Receiver operating characteristic analysis revealed that CDK2, MTHFD1L, SRC, ZWINT, and MAPKAPK5-AS1 had significant diagnostic value in HCC, but further studies are needed to explore their mechanisms in HCC.

Diagnostic value of clusterin immunostaining in hepatocellular carcinoma

BackgroundHistologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC.MethodsEnhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs.ResultsEnhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC.ConclusionsCLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.

C-reactive protein and direct bilirubin as the early diagnostic indicators of primary hepatocellular carcinoma combined with macrovascular invasion

Objective: To explore the early clinical diagnostic indicators in patients with primary hepatocellular carcinoma (HCC) combined with macrovascular invasion. Methods: The clinical data of 180 cases of HCC diagnosed by histopathology examination in the Second Affiliated Hospital of Chongqing Medical University from 2012 to 2019 were retrospectively analyzed. The factors influencing the development of macrovascular invasion in HCC patients were analyzed. The receiver operating characteristic curve (ROC curve) was used to evaluate the sensitivity and specificity. Results: Serum C-reactive protein (CRP) level was significantly correlated with various clinical characteristics of HCC patients, including the maximum tumor diameter, tumor number, and macrovascular invasion. Further analysis of the risk factors showed that serum direct bilirubin and CRP were independent risk factors for macrovascular invasion in HCC patients, with odds ratios of 1.747 (95% CI 1.119-2.728, P = 0.014) and 2.376 (95% CI 1.495-3.775, P < 0.001). ROC curve analysis showed that serum CRP, direct bilirubin, and the combination of the both had certain diagnostic value for hepatocellular carcinoma combined with macrovascular invasion. The area under the curve, sensitivity and specificity was 0.724, 0.668, 0.743, 79.1%, 70.1%, 79.1%, and 61.9%, 62.8%, 67.3%, respectively. Conclusion: The combination of CRP with direct bilirubin can be used as an important clinical diagnostic indicator for early diagnosis and prevention of hepatocellular carcinoma combined with macrovascular invasion.

Neurotrophin 3 hinders the growth and metastasis of hepatocellular carcinoma cells*

Abstract Objective Neurotrophin 3 (NTF3) is involved in numerous biological processes; however, its role in hepatocellular carcinoma (HCC) is not well studied. This study investigated NTF3 function in HCC progression and revealed its underlying molecular mechanisms. Methods The prognostic relevance of NTF3 was determined through a bioinformatical analysis of publicly available TCGA data. Immunohistochemistry of HCC biopsies was performed to explore the expression of NTF3. Cell growth and proliferation were analyzed using a Cell Counting Kit-8 (CCK-8) assay. Cell invasion and migration were analyzed using Boyden Transwell and wound healing assays. Protein expression and mRNA levels were evaluated through immunoblotting and quantitative polymerase chain reaction (qPCR). Cell apoptosis was evaluated with flow cytometry. Results NTF3 expression was significantly lower in HCC tissues than in adjacent non-tumor tissues. Low NTF3 expression was significantly associated with decreased patient survival and specific clinicopathological features. NTF3 overexpression reduced the proliferation, migration, and invasion abilities of HCC cell lines. Conclusion Decreased expression of NTF3 is associated with poor prognosis in HCC patients, likely due to its action in promoting HCC cell proliferation, migration, and invasion. Our findings provide a novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression, suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC.

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma.

BackgroundSpindle pole body component 25 (SPC25) plays a vital role in many cellular processes, such as tumorigenesis. However, the clinical significance of SPC25 in hepatocellular carcinoma (HCC) has not been investigated. This study aimed to explore the expression patterns of SPC25 in HCC and non-neoplastic tissues and to investigate the diagnostic and prognostic values of SPC25.MethodThe expression of SPC25 was examined in 374 HCC issues and 50 non-neoplastic tissues from The Cancer Genome Atlas (TCGA) cohort. The diagnostic and prognostic values of SPC25 were analyzed via receiver operating characteristic (ROC) curve and survival analyses, respectively. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors and to establish a nomogram. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC) database.ResultsThe expression of SPC25 in HCC tissues was significantly higher than that in normal tissues in both cohorts (all P < 0.001). The ROC curve analysis indicated that SPC25 expression has high diagnostic value in HCC with area under the curve (AUC) value of 0.969 (95% confidence interval [CI] [0.948–0.984]) and 0.945 (95% CI [0.920–0.965]) for TCGA and ICGC cohorts, respectively. Patients with HCC exhibiting high SPC25 expression were associated with worse prognosis than those exhibiting low SPC25 expression in both cohorts (all P < 0.001). SPC25 was independently associated with overall survival in both cohorts (all P < 0.001). The concordance indices of the nomogram for predicting overall survival in TCGA and ICGC cohorts were 0.647 and 0.805, respectively, which were higher than those of the American Joint Committee on Cancer (AJCC) staging system.ConclusionSPC25 was upregulated in HCC and independently predicted poor overall survival of patients with HCC. Therefore, SPC25 is an effective diagnostic and prognostic biomarker for HCC. An SPC25-based nomogram was more accurate and useful than the AJCC staging system to predict prognosis of HCC.

HSP90α combined with AFP and TK1 improved the diagnostic value for hepatocellular carcinoma.

Aim: We investigated the effect of the combination of heat shock protein 90α (HSP90α), alpha-fetoprotein (AFP) and thymidine kinase 1 (TK1) in the diagnosis of hepatocellular carcinoma (HCC). Methods & results: A total of409 patients with HCC, 101 patients with benign liver disorder and 78 healthy individuals were retrospectively analyzed. HSP90α level was higher in HCC patients than in controls. The expression of HSP90α showed a positive correlation with tumor stage, differentiation, lymph node metastasis and tumor thrombus formation. The combination of HSP90α, AFP and TK1 improved the diagnostic sensitivity (89.24%) and the area under the receiver operating characteristic curve (0.919). Conclusion: The detection of HSP90α, AFP and TK1 is more efficient than a single tumor marker for the diagnosis of HCC.

Down-regulation of ER-α36 mRNA in serum exosomes of the patients with hepatocellular carcinoma.

Down-regulation of ER-α36 mRNA in serum exosomes of the patients with hepatocellular carcinoma.