scholarly journals Diagnostic value of plasma HSP90α levels for detection of hepatocellular carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wene Wei ◽  
Mengshu Liu ◽  
Shufang Ning ◽  
Jing Wei ◽  
Jianhong Zhong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Heat Shock Protein 90 ◽  
Diagnostic Value ◽  
Initial Diagnosis ◽  
Hepatic Hemangioma ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Major Health Problem ◽  
Healthy Donors ◽  
Potential Biomarker

Abstract Background Hepatocellular carcinoma (HCC) is a major health problem worldwide. However, the popular tumor marker, AFP, lacks sensitivity although its specificity is high. Tissue biopsy is an invasive operation and may increase the risk of needle-track metastases. Heat shock protein 90 (HSP90) is a potential biomarker for tumor diagnosis and prognosis. This study aims to determine whether levels of plasma HSP90α in HCC patients can be used as a cost-effective and simple test for the initial diagnosis of the disease. Methods Plasma samples were collected from 659 HCC patients, 114 secondary hepatic carcinoma (SHC) patients, 28 hepatic hemangioma patients and 230 healthy donors. The levels of HSP90α were measured by ELISA. Results The levels of plasma HSP90α in HCC patients were significantly higher than in healthy donors and in patients with hepatic hemangioma or SHC (144.08 ± 4.98, 46.81 ± 1.11, 61.56 ± 8.20 and 111.96 ± 10.08 ng/mL, respectively; p < 0.05 in all cases). The levels were associated with age (p = 0.001), BCLC stage (p < 0.001), levels of AFP (p < 0.001), tumor size (p < 0.001), tumor number (p < 0.001), PVTT (p < 0.001), EHM (p < 0.001) and Child-Pugh stage in the HCC cohort. In addition, the levels of plasma HSP90α showed an upward trend along with the progression of the BCLC stage. ROC curve analysis showed that compared to AFP (AUC 0.922, 95%CI 0.902–0.938) or HSP90α (AUC 0.836, 95%CI 0.810–0.860), the combination of HSP90α and AFP (AUC0.943, 95%CI 0.925–0.957) significantly improved the diagnostic efficiency for HCC patients. Conclusion The results suggest that plasma Hsp90 α levels can be used as an initial diagnosis for patients with HCC in both rural and cosmopolitan settings.

The diagnostic value of plasma exosomal hsa_circ_0070396 for hepatocellular carcinoma

2021 ◽  
Author(s):  
Lihua Lyu ◽  
Wenjing Yang ◽  
Jiayi Yao ◽  
Hao Wang ◽  
Jie Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Curve Analysis ◽  
Circular Rnas ◽  
Quantitative Real Time Pcr ◽  
Control Groups ◽  
Healthy Donors ◽  
Potential Biomarker

Aim: We aimed to identify novel exosomal circular RNAs for hepatocellular carcinoma (HCC) diagnosis. Materials & methods: Exosomes were extracted and characterized. The expression level of exosomal circRNAs were verified via quantitative real-time PCR. The diagnostic value of candidate circRNAs was evaluated according to the receiver operating characteristic curve analysis. Results: The exosomal circ_0070396 significantly elevated in HCC patients than other control groups and it performed better in distinguishing HCC patients from healthy donors than that of α-fetoprotein. Combination of two above markers exerted greater diagnostic performance. Exosomal circ_0070396 could discriminate HCC individuals from patients with chronic hepatitis B and liver cirrhosis. Intriguingly, exosomal circ_0070396 was positively correlated with HCC progression. Conclusion: Exosomal circ_0070396 may be a potential biomarker for HCC detection and management.

scholarly journals Circulating Exosomal miR-17-92 Cluster Serves as a Novel Non-Invasive Diagnostic Marker for Gastric Cancer Patients

2021 ◽  
Author(s):  
Fei Liu ◽  
Ye Han ◽  
Dongbao Li ◽  
Jun Zhou ◽  
Jingjing Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Quantitative Polymerase Chain Reaction ◽  
Characteristic Curve ◽  
Diagnostic Value ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Non Invasive ◽  
Clinical Diagnostic ◽  
Potential Biomarker

Abstract Gastric cancer (GC) is one of the most common malignant tumors with a leading cause of cancer-related mortality worldwide. Exosomal miRNAs are considered as promising non-invasive biomarkers for the diagnosis of malignant tumors. In this study, we aimed to investigate the expression of exosomal miR-17-92 cluster and develop a potential biomarker for the diagnosis of GC. Exosomal RNAs were extracted and the expression profile of miR-17-92 cluster was detected using quantitative polymerase chain reaction (qRT-PCR). The ROC (receiver-operating characteristic) curve and AUC (area under the ROC curve) analysis were used to explore the diagnostic utility of miRNAs. Statistical was used to analyze the expression of serum exosomal miR-17-92 cluster with the clinical pathological parameters of GC patients. The results showed that the expressions of four members of the exosomal miR-17-92 cluster in the serum samples of GC patients were significantly upregulated compared with those of healthy controls. The AUC for serum exosomal miR-17, miR-18, miR-19a and miR-92 was 0.750 (95%CI=0.626-0.874, sensitivity=84.7%, specificity=70.0%), 0.736 (95%CI=0.590-0.881, sensitivity=88.9%, specificity=65.0%), 0.700 (95%CI=0.562-0.838, sensitivity=62.5%, specificity=80.0%), 0.689 (95%CI=0.567-0.811, sensitivity=45.8%, specificity=90.0%), respectively. The AUC for the newly combined panel consisting of miR-17, miR-18, miR-19a and miR-92 was 0.808 (95%CI=0.680-0.937), with sensitivity of 90.3% and specificity of 70.0%, which showed much higher clinical diagnostic value for GC than any of the four alone or any pair. Besides, the AUC for the newly developed panel consisting of the two traditional tumor biomarkers including CEA (carcinoembryonic antigen) and CA19-9 (carbohydrate antigen 19-9) and the four miR-17-92 cluster members was 0.881 (95%CI, 0.765-0.998) with sensitivity of 91.7% and specificity of 90.0%, which showed the greatest powerful clinical diagnostic value for GC. Moreover, the elevated exosomal miR-17-92 expressions were closely correlated with tumor size, tumor depth, lymph node metastasis, distant metastasis and TNM stage of GC patients. In conclusion, our findings revealed that circulating exosomal miR-17-92 cluster may be used as a novel potential non-invasive biomarker to improve the diagnostic efficiency in GC.

scholarly journals Clinical significance of fucosylated GP73 in the differential diagnosis of hepatocellular carcinoma

2018 ◽  
Vol 33 (4) ◽  
pp. 439-446 ◽  
Author(s):  
Yunsheng Zhao ◽  
Lina Zhang ◽  
Lijing Huo ◽  
Liu Pei ◽  
Qiuping Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Differential Diagnosis ◽  
Roc Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Efficiency ◽  
Roc Curve Analysis ◽  
Diagnostic Significance ◽  
Node Metastasis ◽  
Tumor Node Metastasis Stage ◽  
Normal Controls

Objective: To investigate the clinical value of fucosylated GP73 (Fuc-GP73) levels for differential diagnosis of hepatocellular carcinoma from other liver diseases. Methods: Serum specimens were collected from 50 patients with hepatocellular carcinoma, 60 patients with other digestive system diseases (ODSD), and 40 normal controls. Lectin affinity chromatography column combining with the enzyme-linked immunosorbent assay (ELISA) using the ELISA index was utilized to measure the level of Fuc-GP73. By receiver operating characteristic (ROC) curve analysis its sensitivity and specificity were used to evaluate the diagnostic significance of Fuc-GP73 in hepatocellular carcinoma. Results: The median serum Fuc-GP73 level of hepatocellular carcinoma (20.4 μg/L) was much higher than that of ODSD patients (1.8 μg/L) and the normal controls group (0.3 μg/L), significantly ( P <0.01). There was no significant correlation between serum Fuc-GP73 level and sex, age, and tumor size in the hepatocellular carcinoma group ( P > 0.05); however, it was related to tumor, node, metastasis stage and lymph node metastasis ( P <0.05). The area under the ROC curve (AUC) of Fuc-GP73 to detect hepatocellular carcinoma alone was 0.885; with the prespecified specificity of 95%, the sensitivity and the cutoff value were 82% and 3.1 μg/L. In addition, the combined test of Fuc-GP73 with other biomarkers can improve the clinical diagnostic efficiency; the AUC can reach to 0.983; and with the prespecified specificity of 95% its sensitivity increased to 94%. Conclusion: Fuc-GP73 can act as a superior glycobiomarker for the differential diagnosis of hepatocellular carcinoma; its combined detection with other biomarkers can improve diagnostic accuracy.

scholarly journals Identification of Circulating Exosomal miR-101 and miR-125b Panel Act as a Potential Biomarker for Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Li Sun ◽  
Mu Xu ◽  
Guoying Zhang ◽  
Lin Dong ◽  
Jie Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Roc Curves ◽  
Fold Change ◽  
Diagnostic Utility ◽  
Roc Curve Analysis ◽  
Candidate Mirnas ◽  
Potential Biomarker ◽  
Exosomal Mirnas ◽  
Noninvasive Biomarker ◽  
New Diagnosis

Background. Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high mortality, and there is an urgent need of new diagnosis measures. This study is aimed at investigating whether circulating exosomal miRNAs could act as biomarkers for the diagnosis of HCC. Methods. A four-stage strategy was adopted in this study. Candidate miRNA was selected by comprehensive analysis of four GEO datasets and TCGA database. The expression of candidate miRNAs in serum exosomal samples were examined through qRT-PCR. The diagnostic utility of the final validated miRNAs was examined by receiver operating characteristic (ROC) curve analysis. Results. After synthetical analysis of four GEO datasets, six miRNAs were selected as candidates due to their higher differential fold change. miR-101 and miR-125b were selected as candidate miRNAs to further investigate their potential as biomarkers for HCC due to their differential fold change and their influence on overall survival based on the TCGA database. As a result, miR-101 and miR-125b expressions were remarkably downregulated in both tissues and serum exosomes of patients with HCC. The area under the ROC curves (AUCs) of circulating exosomal miR-101 and miR-125b were 0.894 (95% CI, 0.793–0.994) and 0.812 (95% CI, 0.675–0.950), respectively. The combination of the two miRNAs presented higher diagnostic utility for HCC ( AUC = 0.953 ). Conclusion. The exosomal miR-101 and miR-125b panel in the serum may act as a noninvasive biomarker for HCC detection.

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

2020 ◽  
Vol 26 (2) ◽  
Author(s):  
Dwi Priyadi Djatmiko ◽  
I Putu Adi Santosa ◽  
Elvin Richela Lawanto ◽  
Bogi Pratomo ◽  
Hani Susianti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Marker ◽  
Diagnostic Test ◽  
Method Comparison ◽  
Normal Liver ◽  
Diagnostic Value ◽  
Roc Curve Analysis ◽  
Healthy Control ◽  
Cirrhotic Patients ◽  
Sensitivity Specificity

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.

scholarly journals Fibrinogen Like Protein 1 as a Potential Biomarker for Hepatitis B Virus Related Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Cai Xin ◽  
Tang Dongling ◽  
Chen Juanjuan ◽  
Li Huan ◽  
Hu Yuanhui ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Differential Expression Analysis ◽  
Serum Levels ◽  
Receiver Operating Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diagnostic Efficiency ◽  
Early Screening ◽  
Potential Biomarker ◽  
Benign Liver

Abstract Background There is an urgent need for new serum biomarkers for early screening of HBV-related hepatocellular carcinoma (HCC). Fibrinogen like protein 1 (FGL1) may develop the potential diagnostic value of alpha fetoprotein (AFP) in HBV-related HCC. Methods The TCGA database was used to screen out genes related to liver cancer and perform differential expression analysis. Enzyme-linked immunosorbent assay and chemiluminescence immunoassay were used to detect concentrations of FGL1 and AFP. Using immunofluorescence semi-quantitative method to detect the mean fluorescence intensity of FGL1. Result FGL1 is lower in tumor tissues than in normal tissues. The serum levels of FGL1 and AFP in patients with HBV-related HCC are significantly higher than others for each group. Compared with other groups, the area under the receiver operating curve (AUC) of FGL1 is higher than that of AFP when compared with the normal group, and the AUC of other groups is lower than that of AFP. The combination of the two can increase the AUC to 0.862 (95%CI, 0.786 ~ 0.918) in distinguishing benign liver disease from HBV-related HCC. The specificity of FGL1 and AFP in the diagnosis of HBV-related HCC is 98.39% and 70.97%, respectively. The specificity of the combination was 93.55%. In distinguishing the A and B stages in the BCLC staging, the combination of the two increased the AUC from 0.584 to 0.647. When distinguishing benign liver disease from HBV-related HCC, the AUC of FGL1 reached 0.849, with a specificity of 100%. Conclusion FGL1 can be used as a non-invasive biomarker for HCC. When combined with AFP, the diagnostic efficiency and specificity were improved.

scholarly journals Identification of MCM4 as a Prognostic Marker of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Huandi Zhou ◽  
Le Jiang ◽  
Guohui Wang ◽  
Linlin Su ◽  
Liubing Hou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real Time ◽  
Roc Curve ◽  
Real Time Pcr ◽  
Malignant Tumors ◽  
Nodal Metastasis ◽  
Cellular Heterogeneity ◽  
Survival Prediction ◽  
Roc Curve Analysis ◽  
Potential Biomarker

Object. Hepatocellular carcinoma is one of the most common malignant tumors worldwide owing to its complicated molecular and cellular heterogeneity and its high incidence rate every year. It is an urgent need to search for new efficient molecular markers of HCC to reduce mortality and improve HCC prognosis. In this article, MCM4, a member of a family of proteins closely related to DNA replication and cell proliferation, was selected as a potential biomarker of HCC prognosis. 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 ( AU C MCM 4 = 0.9461 , AU C AFP = 0.7056 ) and GEO (GSE19665: AU C MCM 4 = 0.8800 , AU C AFP = 0.5100 ; GSE64041 AU C MCM 4 = 0.8038 , AU C AFP = 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.

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

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.

scholarly journals Evaluating the diagnostic value of serum Des-γ carboxy prothrombin in the detection of hepatocellular carcinoma

2021 ◽  
Vol 63 (9) ◽  
pp. 33-38
Author(s):  
Dang Quan Nguyen ◽  
◽  
Thi Thanh Thao Nguyen ◽  
Nguyen Thanh Thuy Pham ◽  
Thi Thuy Hang Le ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sensitivity And Specificity ◽  
Diagnostic Value ◽  
Serum Marker ◽  
Serum Markers ◽  
Roc Curve Analysis ◽  
Early Hcc ◽  
High Risk Populations ◽  
Effect Of Treatment ◽  
C 50

Hepatocellular carcinoma (HCC) is amongst the most common cancers in the world and Vietnam. Most HCC patients are diagnosed late, so the effect of treatment is limited. Hence, early diagnosis for high-risk populations using medical imaging and serum markers is very important to control HCC. Recently, α-fetoprotein (AFP) has been popularly used as a serum marker for screening of HCC. Unfortunately, AFP is not trustworthy enough for HCC diagnosis, especially early HCC. Therefore, this study was deployed to estimate the ability of serum Des-γ carboxy prothrombin (DCP) applied in the diagnosis of HCC. DCP and AFP concentration in serum of 50 early HCC patients (stage A), 50 late HCC patients (stage B and C), 50 HBV/HCV-infected patients, and 50 healthy persons were identified. ROC curve analysis manifested that with the cut-off value at 11.93 ng/ml, DCP allowed identifying HCC cases with the sensitivity and specificity of 50 and 94%, respectively. With early HCC, the sensitivity of DCP decreased to 34%, while the specificity was unchanged. In the case of AFP, results showed that the sensitivity and specificity of this marker for HCC were 39 and 95%, with the cut-off value at 952.1 ng/ml. For early HCC, it was impossible to use AFP for diagnosis. The combination of DCP and AFP serum markers in the detection of HCC did not improve the sensitivity of the diagnosis compared to that of DCP alone. The study demonstrated that serum biomarker DCP can be used instead of AFP in the diagnosis of HCC, which improves the diagnostic sensitivity

scholarly journals Detection of MicroRNA in Hepatic Cirrhosis and Hepatocellular Carcinoma in Hepatitis C Genotype-4 in Egyptian Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hala M. Demerdash ◽  
Hend M. Hussien ◽  
Ehab Hassouna ◽  
Emad A. Arida
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C ◽  
Early Detection ◽  
Cell Damage ◽  
Diagnostic Value ◽  
Genotype 4 ◽  
Group Iii ◽  
Group I ◽  
Potential Biomarker ◽  
A Prospective Study

Background. In Egypt, the prevalence of chronic hepatitis C (CHC) infection is 13.8% of whole population and about 80% of the patients with hepatocellular carcinoma have underling hepatitis C. Aim. This study was designed to assess the diagnostic value of plasma miR-122 and miR-21 in patients with CHC, genotype-4, to detect fibrosis progression versus noninvasive indices and their diagnostic value in detection of early stages of hepatocellular carcinoma (HCC). Methodology. A prospective study that included 180 patients, divided into 3 groups: healthy controls (group I), CHC patients (group II), and hepatitis C patients with HCC (group III); all cases were subjected to thorough clinical, radiological, and laboratory investigations. Selected biomarkers were evaluated and correlated with degree of liver damage. Results revealed that miR-122 followed by miR-21 had the highest efficiency in prediction of liver cell damage. Also, miR-21 was strongly correlated with vascular endothelial growth factor (VEGF) and alpha fetoprotein (α-FP) in HCC patients. Conclusions. Plasma miR-122 and miR-21 had strong correlation with degree fibrosis in HCV genotype-4 patients; consequently they can be considered as potential biomarker for early detection of hepatic fibrosis. Moreover, miR-21 can be used as a potential biomarker, for early detection of HCC combined with VEGF and α-FP.

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