Diagnostic Test of PIVKA-II as A Tumor Marker for Hepatocellular Carcinoma (HCC)

Introduction. Alpha-Fetoprotein (AFP) is a tumor marker that has been widely used for HCC, but there has been no increased AFP in 35-45% patients with HCC. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin secreted in HCC and is expected can be used for HCC diagnostic marker. The objective of this study was to compare serum PIVKA-II levels in the patients with HCC, cirrhosis and healthy control and determine the diagnostic value of PIVKA-II for hepatocellular carcinoma. Methods. This was a cross-section analytic observational study to identify the diagnostic value of PIVKA-II for HCC diagnosis. The diagnosis of 20 cirrhotic patients and 15 patients with HCC was established by history taking, physical examination, and additional examination according to the diagnosis criteria. A group of 12 individuals with normal liver function were used as healthy control subjects. Serum PIVKA-II levels were analyzed with immunoassay method. Comparison study used the Independent-Samples Kruskal Wallis Test. ROC curve analysis and 2x2 contingency table was used to calculate sensitivity, specificity, positive and negative predictive value (PPV and NPV).Results. The serum PIVKA-II level in the patients with HCC was significantly higher than in cirrhotic (p = 0,000) and healthy control patients (p = 0,000). Sensitivity, specificity, PPV, and NPV of PIVKA-II for diagnosis of HCC in cirrhotic patients at a cut-off value of 140.85 mAU/mL were 93.33%, 75%, 73.68%, and 93.75%, respectively (AUC = 0.87).Conclusions and Suggestions. PIVKA-II has high diagnostic value for HCC diagnosis. Diagnostic test that compare serum PIVKA-II level in any size of HCC nodules may be needed in the future.

Download Full-text

SUMO-Activating Enzyme Subunit 1 (SAE1) Is a Promising Diagnostic Cancer Metabolism Biomarker of Hepatocellular Carcinoma

Cells ◽

10.3390/cells10010178 ◽

2021 ◽

Vol 10 (1) ◽

pp. 178

Author(s):

Jiann Ruey Ong ◽

Oluwaseun Adebayo Bamodu ◽

Nguyen Viet Khang ◽

Yen-Kuang Lin ◽

Chi-Tai Yeh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Metabolism ◽

Interaction Analysis ◽

Normal Liver ◽

Diagnostic Value ◽

Vital Role ◽

Regulation Of Transcription ◽

Dependent Manner ◽

Post Translational Modification ◽

Characteristic Analysis

Hepatocellular carcinoma (HCC) is one of the most diagnosed malignancies and a leading cause of cancer-related mortality globally. This is exacerbated by its highly aggressive phenotype, and limitation in early diagnosis and effective therapies. The SUMO-activating enzyme subunit 1 (SAE1) is a component of a heterodimeric small ubiquitin-related modifier that plays a vital role in SUMOylation, a post-translational modification involving in cellular events such as regulation of transcription, cell cycle and apoptosis. Reported overexpression of SAE1 in glioma in a stage-dependent manner suggests it has a probable role in cancer initiation and progression. In this study, hypothesizing that SAE1 is implicated in HCC metastatic phenotype and poor prognosis, we analyzed the expression of SAE1 in several cancer databases and to unravel the underlying molecular mechanism of SAE1-associated hepatocarcinogenesis. Here, we demonstrated that SAE1 is over-expressed in HCC samples compared to normal liver tissue, and this observed SAE1 overexpression is stage and grade-dependent and associated with poor survival. The receiver operating characteristic analysis of SAE1 in TCGA−LIHC patients (n = 421) showed an AUC of 0.925, indicating an excellent diagnostic value of SAE1 in HCC. Our protein-protein interaction analysis for SAE1 showed that SAE1 interacted with and activated oncogenes such as PLK1, CCNB1, CDK4 and CDK1, while simultaneously inhibiting tumor suppressors including PDK4, KLF9, FOXO1 and ALDH2. Immunohistochemical staining and clinicopathological correlate analysis of SAE1 in our TMU-SHH HCC cohort (n = 54) further validated the overexpression of SAE1 in cancerous liver tissues compared with ‘normal’ paracancerous tissue, and high SAE1 expression was strongly correlated with metastasis and disease progression. The oncogenic effect of upregulated SAE1 is associated with dysregulated cancer metabolic signaling. In conclusion, the present study demonstrates that SAE1 is a targetable cancer metabolic biomarker with high potential diagnostic and prognostic implications for patients with HCC.

Download Full-text

Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0152 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Lei Xi ◽

Chunqing Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Receiver Operating Characteristic Curves ◽

Sensitivity Specificity ◽

Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

Download Full-text

Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02124-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiao-hong Mao ◽

Qiang Ye ◽

Guo-bing Zhang ◽

Jin-ying Jiang ◽

Hong-ying Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

High Sensitivity ◽

Breast Cancer Diagnosis ◽

Diagnostic Value ◽

Methylation Pattern ◽

Clinical Value ◽

Roc Curve Analysis ◽

Differentially Methylated Genes ◽

Sensitivity Specificity

Abstract Background Aberrant DNA methylation is significantly associated with breast cancer. Methods In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. Results In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994–1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976–1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. Conclusions Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

Download Full-text

The diagnostic and prognostic value of H2AFY in hepatocellular carcinoma

10.21203/rs.3.rs-17889/v2 ◽

2020 ◽

Author(s):

xuyang ma ◽

Ying Ding ◽

Li Zeng

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Prognostic Value ◽

Clinical Characteristics ◽

Cox Regression ◽

Normal Liver ◽

Diagnostic Value ◽

The Relationship ◽

Diagnostic And Prognostic Value

Abstract Background: The 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. Methods: The 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. Result: Compared 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. Conclusion: Our 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.

Download Full-text

Diagnostic Value of Clusterin Immunostaining in Hepatocellular Carcinoma

10.21203/rs.3.rs-27056/v1 ◽

2020 ◽

Author(s):

Yuan Li ◽

Fangfang Liu ◽

Wendi Zhou ◽

Sharon Zhang ◽

Peiguo Chu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Expression Pattern ◽

Staining Pattern ◽

Hepatocellular Adenoma ◽

Normal Liver ◽

Diagnostic Value ◽

Tissue Samples ◽

Regenerative Nodules ◽

Well Differentiated ◽

Mass Lesions

Abstract Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenging. 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.Methods Enhanced 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.Results Enhanced 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.Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.

Download Full-text

Diagnostic Value of Clusterin Immunostaining in Hepatocellular Carcinoma

10.21203/rs.3.rs-27056/v3 ◽

2020 ◽

Author(s):

Yuan Li ◽

Fangfang Liu ◽

Wendi Zhou ◽

Sharon Zhang ◽

Peiguo Chu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Expression Pattern ◽

Staining Pattern ◽

Hepatocellular Adenoma ◽

Normal Liver ◽

Diagnostic Value ◽

Tissue Samples ◽

Multiple Organs ◽

Regenerative Nodules ◽

Mass Lesions

Abstract Background: Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenging. 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. Methods: Enhanced 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. Results: Enhanced 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. Conclusions: CLU 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.

Download Full-text

Estimation of serum Alpha feto-protein (AFP), interlukin-6 and Des-?-carboxyprothrombin (DCP) in case of hepatocellular carcinoma

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v15i2.19602 ◽

2016 ◽

Vol 15 (2) ◽

pp. 230-233 ◽

Cited By ~ 1

Author(s):

Syed Shahzadul Haque ◽

Rekha Kumari ◽

Ali Muzaffar ◽

Uday Kumar ◽

Anand Sharan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Marker ◽

Medical Science ◽

Diagnostic Value ◽

Incidence Rates ◽

Intrahepatic Metastasis ◽

Sub Saharan Africa ◽

Primary Hepatocellular Carcinoma ◽

Enzyme Linked Immunosorbent Assay ◽

Primary Malignancy

Background: Hepatocellular carcinoma (HCC) is one the most common primary malignancy of the liver and represents the third leading cause of cancer-related deaths worldwide. Incidence rates are highest in East Asia and Sub-Saharan Africa. A number of evidence suggests a possible role of interleukin-6 (IL-6), ?-Fetoprotein (AFP) and Des-?-carboxyprothrombin (DCP) in the pathogenesis of hepatocellular carcinoma (HCC). The high DCP may be related to increase tumour behaviour, such as the presence of vascular invasion and intrahepatic metastasis of HCC cells. Patients and methods: We studied IL-6, AFP and DCP in patients with HCC or in healthy controls. AFP was measured by chemiluminescent immunoassay; Serum IL-6 and DCP were measured by enzyme linked immunosorbent assay in 30 patients with primary hepatocellular carcinoma and 30 normal subjects.Results: IL-6, AFP and DCP were found high in the serum of patients initially diagnosed with HCC (18±9.8), (315.99±594.62) and (26.15±5.01) respectively compared with healthy subjects (4.29±2.10), (3.13±1.27) and (4.25±1.22). A significant positive correlation was found between mean levels of IL- 6 & AFP in HCC (P < 0.05), Combination of IL-6, AFP and DCP improved the sensitivity in diagnosing HCC or predicting future HCC development. Conclusions: IL-6, DCP along with AFP could be considered a promising tumor marker for HCC. DCP is a well recognized tumor marker for the screening and diagnosis of HCC. In particular, the diagnostic value of the test is significantly increased when combined with AFP.Bangladesh Journal of Medical Science Vol.15(2) 2016 p.230-233

Download Full-text

Surgical Therapy of Hepatocellular Carcinoma in the Cirrhotic Liver

Swiss Surgery ◽

10.1024/1023-9332.5.3.107 ◽

1999 ◽

Vol 5 (3) ◽

pp. 107-110 ◽

Cited By ~ 8

Author(s):

Fan

Keyword(s):

Hepatocellular Carcinoma ◽

Mortality Rate ◽

Surgical Technique ◽

Hospital Mortality ◽

Normal Liver ◽

Liver Parenchyma ◽

Ischaemic Injury ◽

Liver Remnant ◽

Cirrhotic Patients ◽

Major Hepatectomies

Hepatectomy for hepatocellular carcinoma (HCC) associated with cirrhosis was considered by some surgeons contraindicated because the hospital mortality rate, especially for major hepatectomy, was very high. The author reported his surgical approach to hepatectomy associated with cirrhosis. Between 1989 and 1995, 66 major hepatectomies and 32 minor hepatectomies were performed in 98 cirrhotic patients. The selection of patients for hepatectomy was based on results of indocyanine green clearance test. The surgical technique was designed to reduce blood loss, ischaemic injury to the liver remnant and preservation of liver parenchyma. The postoperative care was designed to maintain or improve liver function. By such an approach, the hospital mortality rate of the cirrhotic patients having hepatectomy decreased from 40% in 1989 to 5% in 1995. The 5-year survival rate also improved to 41.2%, which is not statistically different from that of those with a normal liver or chronic hepatitis. With refinement in surgical technique and perioperative care, patients with cirrhosis can also benefit from hepatectomy for HCC.

Download Full-text

Low UGP2 Expression Is Associated with Tumour Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2020/3231273 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Qiuyue Hu ◽

Shen Shen ◽

Jianhao Li ◽

Liwen Liu ◽

Xin Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Poor Prognosis ◽

Cox Regression ◽

Tumour Progression ◽

Enrichment Analysis ◽

Malignant Tumour ◽

Diagnostic Value ◽

Gene Set Enrichment Analysis ◽

Uridine Diphosphate ◽

Roc Curve Analysis

Hepatocellular carcinoma (HCC) is a malignant tumour associated with a high mortality rate and poor prognosis worldwide. Uridine diphosphate-glucose pyrophosphorylase 2 (UGP2), a key enzyme in glycogen biosynthesis, has been reported to be associated with the occurrence and development of various cancer types. However, its diagnostic value and prognostic value in HCC remain unclear. The present study observed that UGP2 expression was significantly downregulated at both the mRNA and protein levels in HCC tissues. Receiver operating characteristic (ROC) curve analysis revealed that UGP2 may be an indicator for the diagnosis of HCC. In addition, Kaplan-Meier and Cox regression multivariate analyses indicated that UGP2 is an independent prognostic factor of overall survival (OS) in patients with HCC. Furthermore, gene set enrichment analysis (GSEA) suggested that gene sets negatively correlated with the survival of HCC patients were enriched in the group with low UGP2 expression levels. More importantly, a significant correlation was identified between low UGP2 expression and fatty acid metabolism. In summary, the present study demonstrates that UGP2 may contribute to the progression of HCC, indicating a potential therapeutic target for HCC patients.

Download Full-text