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

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

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Diagnostic value of alpha-fetoprotein, Lens culinaris agglutinin-reactive alpha-fetoprotein, and des-gamma-carboxyprothrombin in hepatitis B virus-related hepatocellular carcinoma

Journal of International Medical Research ◽

10.1177/0300060519889270 ◽

2019 ◽

Vol 48 (3) ◽

pp. 030006051988927

Author(s):

Ting Song ◽

Lili Wang ◽

Bin Su ◽

Weiping Zeng ◽

Taiyi Jiang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Sensitivity And Specificity ◽

Lens Culinaris ◽

Diagnostic Value ◽

Alpha Fetoprotein ◽

Lens Culinaris Agglutinin ◽

B Virus ◽

Early Hcc

Objective This study aimed to explore the use of different combinations of alpha-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP (AFP-L3), and des-gamma-carboxyprothrombin (DCP) for the early diagnosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis (LC). Methods There were 167 subjects, including 100 with HCC and 67 with LC, who were enrolled into this study. Serum AFP, AFP-L3, and DCP levels were detected by chemiluminescent enzyme immunoassay and analyzed using the receiver operating characteristics (ROC) method. Results The sensitivity and specificity of AFP and DCP for differentiating between early HCC and HBV-associated LC were 51.5% and 92.5%, and 60.0% and 84.7%, respectively. Comparative analysis of ROC curves showed no significant difference in the area under the curve (AUC) for AFP and DCP. Moreover, the combination of AFP and DCP showed the largest AUC value with a diagnostic sensitivity and specificity of 67% and 83.1%, respectively. Conclusion These results suggest that AFP is the best single biomarker for distinguishing between HBV-associated LC and early HCC induced by HBV. However, the combination of AFP and DCP can enhance the diagnostic value of AFP for differentiating between these diseases.

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Can Serum Glypican-3 Be a Biomarker for Effective Diagnosis of Hepatocellular Carcinoma? A Meta-Analysis of the Literature

Disease Markers ◽

10.1155/2014/127831 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Sheng-Li Yang ◽

Xiefan Fang ◽

Zao-Zao Huang ◽

Xiang-Jie Liu ◽

Zhi-Fan Xiong ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Sensitivity And Specificity ◽

Meta Analysis ◽

Diagnostic Value ◽

Healthy Individuals ◽

Subgroup Analyses ◽

Effective Diagnosis ◽

Diagnostic Index

Objective. This review is to evaluate the diagnostic value of serum GPC3 for hepatocellular carcinoma (HCC) due to conflicting results reported.Methods. NCBI PubMed and Embase were comprehensively searched for studies that have used serum GPC3 level as a diagnostic index for HCC. The quality of the included studies was assessed. Subgroup analyses were conducted to evaluate the sensitivity and specificity of GPC3 as a HCC marker. Statistical analysis was performed with the software STATA version 12.0.Results. A total of 22 studies were included. The qualities of included studies were relatively poor. Among them, 18 studies have shown that serum GPC3 is a specific biomarker for HCC, and the pooled sensitivity and specificity of these studies were 69 and 93%, respectively. The other 4 studies have reported conflicting results, which were not caused by races, infection status of HBV and HCV, or assay reagents but due to one common experimental design of enrolling liver cirrhosis patients as control subjects.Conclusions. This meta-analysis indicates that serum GPC3 is elevated in HCC patients compared with healthy individuals, but more studies are needed to evaluate its effectiveness to differentially diagnose HCC and liver cirrhosis.

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Diagnostic Value of Imaging Methods in the Histological Four Grading of Hepatocellular Carcinoma

Diagnostics ◽

10.3390/diagnostics10050321 ◽

2020 ◽

Vol 10 (5) ◽

pp. 321 ◽

Cited By ~ 5

Author(s):

Feiqian Wang ◽

Kazushi Numata ◽

Masayuki Nakano ◽

Mikiko Tanabe ◽

Makoto Chuma ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Area Under The Curve ◽

Diagnostic System ◽

Diagnostic Value ◽

Imaging Method ◽

Multicenter Studies ◽

Diagnostic Efficacy ◽

Portal Phase ◽

Contrast Enhanced ◽

Early Hcc

We attempted to establish an ultrasound (US) imaging-diagnostic system for histopathological grades of differentiation of hepatocellular carcinoma (HCC). We conducted a retrospective study of histopathologically confirmed 200 HCCs, classified as early (45 lesions), well- (31 lesions), moderately (68 lesions) or poorly differentiated (diff.) (56 lesions) HCCs. We performed grayscale US to estimate the presence/absence of halo and mosaic signs, Sonazoid contrast-enhanced US (CEUS) to determine vascularity (hypo/iso/hyper) of lesion in arterial and portal phase (PP), and echogenicity of lesion in post-vascular phase (PVP). All findings were of significance for the diagnosis of some (but not all) histological grades (p < 0.001–0.05). Combined findings with a relatively high diagnostic efficacy for early, poorly and moderately diff. HCC were a combination of absence of halo sign and isoechogenicity in PVP of CEUS (accuracy: 93.0%, AUC: 0.908), hypovascularity in PP (accuracy: 78.0%, area under the curve (AUC): 0.750), and a combination of isovascularity in PP and hypoechogenicity in PVP (accuracy: 75.0%, AUC: 0.739), respectively. On the other hand, neither any individual finding nor any combination of findings yielded an AUC of over 0.657 for the diagnosis of well-diff. HCC. Our study provides encouraging data on Sonazoid CEUS in the histological differential diagnosis of HCC, especially in early HCC, and the effectiveness of this imaging method should be further proved by prospective, large sample, multicenter studies.

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

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v26i2.1436 ◽

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.

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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.

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Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Early Hepatocellular Carcinoma

The International Journal of Biological Markers ◽

10.5301/jbm.5000015 ◽

2013 ◽

Vol 28 (3) ◽

pp. 286-297 ◽

Cited By ~ 17

Author(s):

Hao Yang ◽

Guo-Dong Chen ◽

Feng Fang ◽

Zhen Liu ◽

Stephanie Hiu Yan Lau ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Liver Tumors ◽

Serum Levels ◽

Serum Marker ◽

High Serum ◽

Fresh Tissue ◽

Diagnostic Efficacy ◽

Early Hcc ◽

Dickkopf 1

Background and aims The aim of the present study was to evaluate serum Dickkopf-1 (Dkk-1) as a marker for early detection of hepatocellular carcinoma (HCC), as well as for prognostic prediction of early HCC after hepatic resection. Methods One-hundred and four cases of matched fresh tissue specimens of early HCC and adjacent non-tumorous liver tissue (ANLT) were obtained for RT-PCR, qRT-PCR, western blot and immunohistochemistry assays. Sera were collected from patients with early HCC (n=184), benign liver tumors (n=29), cirrhosis (n=174), non-cirrhotic hepatitis B (n=193), and from healthy individuals (n=202). The levels of Dkk-1 and alpha fetoprotein (AFP) were measured. Results The Dkk-1 mRNA and protein levels were both upregulated in early HCC. Serum levels of Dkk-1 in patients with early HCC were significantly higher than in the other 4 groups (p<0.001). Dkk-1 had a better sensitivity and accuracy than AFP (p<0.05). More importantly, 73.1% of the patients negative for AFP could be diagnosed with early HCC using Dkk-1. A combination of Dkk-1 and AFP further improved the diagnostic efficacy. Patients with a high serum Dkk-1 level had poorer overall and relapse-free survivals than those with a low Dkk-1 level (p=0.028 and p=0.045, respectively). These results were shown in a testing cohort and confirmed in a validation cohort of patients. Univariable and multivariable Cox regression analyses showed serum Dkk-1 level to be an independent prognostic factor for overall survival. Conclusions Our data show that Dkk-1 is a diagnostic and prognostic serologic marker for early HCC.

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Evaluation of Serum GDF15, AFP, and PIVKA-II as Diagnostic Markers for HBV-Associated Hepatocellular Carcinoma

Laboratory Medicine ◽

10.1093/labmed/lmaa089 ◽

2020 ◽

Author(s):

Juanjuan Chen ◽

Dongling Tang ◽

Chu Xu ◽

Zhili Niu ◽

Huan Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B ◽

Diagnostic Accuracy ◽

Roc Curve ◽

Operating Characteristic ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

Serum Marker ◽

B Virus

Abstract Objective To evaluate the potential diagnostic value of growth differentiation factor 15 (GDF15) alone and its combination with protein induced by vitamin K absence-II (PIVKA-II) and alpha-fetoprotein (AFP) for hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Methods Serum levels of GDF15, PIVKA-II, and AFP were measured in 110 patients with HBV-associated HCC, 70 patients with HBV-related liver cirrhosis (LC), 70 patients with chronic hepatitis B (CHB), and 110 healthy patients. Results Serum GDF15 was positively related to the levels of PIVKA-II and AFP in patients with HCC (r = 0.352 and r = 0.378; all P <.0001). When the receiver operating characteristic (ROC) curve was plotted for patients with HCC vs all control patients, serum GDF15 had diagnostic parameters of an area under the curve (AUC) of 0.693, a sensitivity of 67.30%, and a specificity of 66.70%, which were lower than parameters for PIVKA-II and AFP (all P <.0001). When the ROC curve was plotted for patients with HCC vs patients with LC, the combination of GDF15 and PIVKA-II had the highest diagnostic accuracy of AUC and specificity as compared with other combinations (all P <.0001). Conclusion We found that GDF15 is a potent serum marker for the detection of HBV-associated HCC and that PIVKA-II combined with GDF15 can improve diagnostic accuracy for HBV-associated HCC.

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Model to Predict Overall Survival in Patients With Hepatocellular Carcinoma After Curative Hepatectomy

Frontiers in Oncology ◽

10.3389/fonc.2020.537526 ◽

2021 ◽

Vol 10 ◽

Author(s):

Li-xiang Zhang ◽

Pan-quan Luo ◽

Lei Chen ◽

Dong-da Song ◽

A-man Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Scoring System ◽

External Validation ◽

Area Under The Curve ◽

Serum Markers ◽

Validation Dataset ◽

Roc Curve Analysis ◽

Scoring Model ◽

New Scoring ◽

Curative Hepatectomy

BackgroundThe prognosis of patients with hepatocellular carcinoma (HCC) remains difficult to accurately predict. The purpose of this study was to establish a prognostic model for HCC based on a novel scoring system.MethodsFive hundred and sixty patients who underwent a curative hepatectomy for treatment of HCC at our hospital between January 2007 and January 2014 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. The nomogram construction was based on Cox proportional hazard regression models, and the development of the new scoring model was analyzed using receiver operating characteristic (ROC) curve analysis and then compared with other clinical indexes. The novel scoring system was then validated with an external dataset from a different medical institution.ResultsMultivariate analysis showed that tumor size, portal vein tumor thrombus (PVTT), invasion of adjacent tissues, microvascular invasion, and levels of fibrinogen and total bilirubin were independent prognostic factors. The new scoring model had higher area under the curve (AUC) values compared to other systems, and the C-index of the nomogram was highly consistent for evaluating the survival of HCC patients in the validation and training datasets, as well as the external validation dataset.ConclusionsBased on serum markers and other clinical indicators, a precise model to predict the prognosis of patients with HCC was developed. This novel scoring system can be an effective tool for both surgeons and patients.

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Platelets’ RNA as biomarker trove for differentiation of early-stage hepatocellular carcinoma from underlying cirrhotic nodules

PLoS ONE ◽

10.1371/journal.pone.0256739 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0256739

Author(s):

Walifa Waqar ◽

Sidra Asghar ◽

Sobia Manzoor

Keyword(s):

Hepatocellular Carcinoma ◽

Late Stage ◽

Liquid Biopsy ◽

Early Stage ◽

Quantitative Real Time Pcr ◽

Roc Curve Analysis ◽

Mrna Content ◽

Early Hcc ◽

Rising Incidence ◽

Specific Mrna

Background & aims Among the multiplicity of factors involved in rising incidence of hepatocellular carcinoma (HCC)-the second deadliest cancer, late diagnosis of early-stage HCC nodules originating from late-stage cirrhotic nodules is the most crucial. In recent years, Tumor-educated platelets (TEPs) have emerged as a strong multimodal tool to be used in liquid-biopsy of cancers because of changes in their mRNA content. This study assessed the reliability of selected mRNA repertoire of platelets as biomarkers to differentiate early HCC from late-stage cirrhotic nodules. Methods Quantitative real time PCR (qRT-PCR) was used to evaluate expression levels of selected platelets-specific mRNA between HCC patients compared to cirrhosis patients. ROC curve analysis assessed the sensitivity and specificity of the biomarkers. Results RhoA, CTNNB1 and SPINK1 showed a significant 3.3-, 3.2- and 3.18-folds upregulation, respectively, in HCC patients compared to cirrhosis patients while IFITM3 and SERPIND1 presented a 2.24-fold change. Strikingly, CD41+ platelets also demonstrated a marked difference of expression in HCC and cirrhosis groups. Conclusions Our study reports liquid biopsy-based platelets mRNA signature for early diagnosis of HCC from underlying cirrhotic nodules. Moreover, differential expression of CD41+ platelets in two groups provides new insights into a probable link between CD41 expression on platelets with the progression of cirrhosis to HCC.

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Detection of Serum KL-6 and SARS-CoV-2 Antibody in Patients with Coronavirus Disease 2019 and the Diagnostic Value in Severe Disease

10.21203/rs.3.rs-125188/v1 ◽

2020 ◽

Author(s):

Huiyan Wang ◽

Lichang Chen ◽

Yang Zhang ◽

Long Liu ◽

Meimei Xu ◽

...

Keyword(s):

Sensitivity And Specificity ◽

Early Stage ◽

Severe Disease ◽

Immunoglobulin A ◽

Clinical Manifestations ◽

Serum Levels ◽

Diagnostic Value ◽

Serum Markers ◽

Diagnostic Efficacy ◽

Risk Of Death

Abstract Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant threat to human health, but its clinical manifestations vary greatly among individuals. Early detection and treatment are important for severely ill patients to improve their prognosis and reduce the risk of death. Methods: In the present study, serum markers were detected and analyzed in moderately ill and severely ill patients. Results: The results found that there were statistically significant differences in age, serum Krebs von den Lungen-6 (KL-6) and Immunoglobulin A (IgA) levels between severely ill patients and moderately ill patients (P < 0.05). The cut-off of using KL-6 alone for the diagnosis of severely ill patients was 298.91 U/mL, with an AUC of 0.737, a sensitivity of 100%, and a specificity of 43%. When the diagnosis was performed using KL-6 in combination with Interleukin-6 (IL-6), an indicator of infection, the AUC was 0.776, with a sensitivity and specificity of 82% and 69%, respectively. When the three above were used in combination for diagnosis, the AUC was 0.785, and the sensitivity and specificity were 100% and 59%, respectively. After rehabilitation, the serum levels of KL-6, C-reactive protein (CRP), as well as antibodies, IgA, IgM and IgG, were significantly lower than those in the early stage of hospitalization. Conclusion: In the present study, KL-6 and IgA were found to have some diagnostic efficacy for severely ill patients with COVID-19, but larger cohort studies are still needed for further confirmation, which in turn improves the diagnostic and therapeutic efficiency of severely ill patients.

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