Evaluation of serum dickkopf-1 as a tumor biomarker for diagnosis and prognosis of hepatocellular carcinoma in patients with cirrhotic liver (original) (raw)
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156 Dickkopf-1 : As a Diagnostic and Prognostic Serum Marker for Hepatocellular Carcinoma
2016
Background and study aim: Hepatocellular carcinoma (HCC) accounts for 70-80% of all liver cancers and the 5-year survival is only 3-5%. This bad prognosis is due to the lack of an effective method for early diagnosis. So, only 30-40% of patients with HCC are suitable for curative treatments at the time of diagnosis. Thus, there is a great need for tools to diagnose HCC early especially in cirrhotic patients. The aim of this work is to assess the validity of serum DKK1 as a diagnostic marker for HCC and to assess prognostic value of serum DKK1 in predicting treatment response, complication and survival in HCC patients. Patients and Methods: This study included 60 Patients divided into two groups. Group A: consisted of 30 patients with post hepatitic C and/or B liver cirrhosis. Group B: consisted of 30 patients with HCC on top of post hepatitic C and/or B liver cirrhosis. Group B patients underwent either radiofrequency ablation or ethanol injection. Clinical assessment, routine laboratory evaluation, CT studies and measurement of serum alpha-fetoprotein (AFP) and DKK1 were performed to all patients and repeated to group B patients 1 and 3 months after treatment. Results: The optimum cut off value of DKK1 for diagnosis of HCC was 4.3 ng/mL (AUC 0.89, sensitivity 66.7% and specificity 96.6%) (P<0.001). While, the optimum cut off value for AFP was > 101 ng/mL with 90% sensitivity and 75.9% specificity (p<0.001). Testing of both DKK1 and AFP increased the diagnostic accuracy for HCC (AUC 0.901, sensitivity 93.3%, and specificity 75.9) (P<0.001). Serum DKK1 level significantly decreases after HCC treatment with either radiofrequency ablation or ethanol injection (P<0.001). Conclusion: Testing of both DKK1 and AFP significantly increased the diagnostic accuracy for HCC. Meanwhile, DKK1 can be used alone for HCC diagnosis even in HCC with inconclusive AFP. DKK1 has a promising prognostic value and can be used for follow up of HCC patients who underwent loco-regional treatment.
Dickkopf-1: As a Diagnostic and Prognostic Serum Marker for Hepatocellular Carcinoma
2016
Background and study aim: Hepatocellular carcinoma (HCC) accounts for 70-80% of all liver cancers and the 5-year survival is only 3-5%. This bad prognosis is due to the lack of an effective method for early diagnosis. So, only 30-40% of patients with HCC are suitable for curative treatments at the time of diagnosis. Thus, there is a great need for tools to diagnose HCC early especially in cirrhotic patients. The aim of this work is to assess the validity of serum DKK1 as a diagnostic marker for HCC and to assess prognostic value of serum DKK1 in predicting treatment response, complication and survival in HCC patients. Patients and Methods: This study included 60 Patients divided into two groups. Group A: consisted of 30 patients with post hepatitic C and/or B liver cirrhosis. Group B: consisted of 30 patients with HCC on top of post hepatitic C and/or B liver cirrhosis. Group B patients underwent either radiofrequency ablation or ethanol injection. Clinical assessment, routine laboratory evaluation, CT studies and measurement of serum alpha-fetoprotein (AFP) and DKK1 were performed to all patients and repeated to group B patients 1 and 3 months after treatment. Results: The optimum cut off value of DKK1 for diagnosis of HCC was 4.3 ng/mL (AUC 0.89, sensitivity 66.7% and specificity 96.6%) (P<0.001). While, the optimum cut off value for AFP was > 101 ng/mL with 90% sensitivity and 75.9% specificity (p<0.001). Testing of both DKK1 and AFP increased the diagnostic accuracy for HCC (AUC 0.901, sensitivity 93.3%, and specificity 75.9) (P<0.001). Serum DKK1 level significantly decreases after HCC treatment with either radiofrequency ablation or ethanol injection (P<0.001). Conclusion: Testing of both DKK1 and AFP significantly increased the diagnostic accuracy for HCC. Meanwhile, DKK1 can be used alone for HCC diagnosis even in HCC with inconclusive AFP. DKK1 has a promising prognostic value and can be used for follow up of HCC patients who underwent loco-regional treatment.
Serum Dickkopf-1 as A Biomarker for The Diagnosis and Prognosis of Hepatocellular Carcinoma
2019
Background: Hepatocellular carcinoma is one of the commonest cancers in world. It is one of the major health problems and its incidence is increasing. The main routinely used parameter for diagnosis of HCC is AFP, also it can be elevated in the liver cirrhosis. It represents a liver cell specific, not a tumor specific marker, for these reasons, we suggest use AFP as a supplementary marker for HCC diagnosis. So, identification of a sensitive biomarker to improve early diagnosis of HCC is in need. Aim of the work: this study was aimed to evaluate the clinical significance of serum Dickkopf-1 (DKK1) as a diagnostic and prognostic marker in hepatocellular carcinoma. Patients and Methods: in this study 100 subjects were included and divided into 3 groups, Group I: included 50 patients with HCC, and divided into 2 subgroups according to Barcelona Clinic Liver Cancer (BCLC) into early HCC (24 patients) and late HCC (18 patients). Group II: included 25 patients with liver cirrhosis. Group III: included 25 healthy subjects (control). Clinical assessment, routine laboratory evaluation, CT scan and measurements of serum alpha-fetoprotein (AFP) and DKK1 were performed to all patients and repeated to group I patients 1 month after treatment. Results: the current study showed that Serum DKK1 was significantly elevated in HCC group compared to liver cirrhosis and healthy control groups, with increased level in late than early stage. The optimum cut off values of DKK1 for diagnosis of HCC was 1.92 ng/mL (AUC 0.926, sensitivity 88% and specificity 83%). While the optimum cut off value for AFP was 102 ng/mL (AUC 0.904, 71% sensitivity and 84% specificity). Testing of both serum DKK1 and AFP increased the diagnostic accuracy for HCC (AUC 0.964, sensitivity 91%, and specificity 90%). Serum DKK1 level significantly decreases after HCC treatment with radio-frequency ablation. Conclusion: It could be concluded that Testing of both serum DKK1 and AFP significantly increased the diagnostic accuracy for HCC. Meanwhile, DKK1 can be used alone for diagnosis of HCC even in HCC with inconclusive AFP. Serum DKK1 might be a potential diagnostic and prognostic marker for HCC.
ASSESSMENT OF DICKKOPF-1 AS A BIOMARKER OF HEPATOCELLULAR CARCINOMA IN EGYPTIANS.
International Journal of Advanced Research (IJAR), 2019
Background: Hepatocellular carcinoma (HCC) is considered to be one of the most aggressive malignancies. Several studies have shown that dickkopf-1 (DKK1) is overexpressed in HCC tissue. Objective and Methods: The present study aimed at demonstrating the diagnostic efficacy of serum levels of DKK1 in HCC in comparison to alpha fetoprotein (AFP). Eighty individuals were included in the present study, and categorized to three groups: Group I: 40 patients with HCC on top of viral liver cirrhosis, Group II: 20 patients with viral induced liver cirrhosis without HCC, and Group III: 20 healthy individuals. Serum levels of AFP and DKK1 were measured and compared in all groups. Results:The values of AFP and DKK1 in group I were statistically higher than those in groups II and III. At the optimum value of 11.7 ng/ml, the sensitivity and specificity of serum AFP were 70.0% and 87.5%, respectively. DKK1 had higher sensitivity (80.0%) and specificity (90.0%) than AFP, at the cut-off value of 1.28 ng/ml for the diagnosis of HCC. Area under the curve (AUC) was higher in DKK1 (0.811) than AFP (0.779) when discriminating between group I and other groups. It was noted that the combination of both markers had a higher sensitivity and specificity, and a larger AUC than each alone. Conclusion: Serum DKK1 is a promising biomarker and is superior to AFP for HCC diagnosis. Combination of AFP and DKK1 improved the accuracy of HCC diagnosis in relation to each test alone.
Cancer Management and Research, 2019
Background: This study aimed to evaluate the role of Dickopff 1 (DKK1) serum levels as a marker for early detection of hepatocellular carcinoma (HCC) and to compare it with alphafetoprotein (AFP) after non-surgical intervention (microwave ablation, radiofrequency ablation) in HCC. Patients and methods: This prospective study was conducted in Al-Mahalla hepatology teaching hospital from June 2015 to June 2017. One hundred and twenty patients were included. They were classified into four groups: Group A: 40 patients with chronic liver disease; Group B: 40 patients with HCC which were divided into 2 main sub groups, group Ba which included HCC patients who were not eligible for ablative therapy and group Bb which included HCC patients who were eligible for ablative therapy; Group C: 20 healthy control subjects matched for age and sex; Group D: 20 HCC patients with negative AFP, DKK1 was done for them. Results: There was a highly significant difference (p < 0.001) between groups regarding serum level of Dickpoff 1 with mean of 1 ng/mL in group A (cirrhotic), 2.38 ng/mL in group B (HCC), and 1.83 ng/mL in group D (AFP negative HCC) in comparison to control group C with mean of 0.54 ng/mL. There was a highly statistically significant difference (p value less =0.01) in the studied groups regarding serum Dickpoff 1 before and after intervention with a mean of 2.38 ng/mL before intervention and mean of 1.37 ng/mL after 1 month of intervention. Conclusion: Serum Dkk-1 has higher sensitivity, specificity, and accuracy in early diagnosis of HCC than AFP.
Bulletin of Egyptian Society for Physiological Sciences
Early detection of hepatocellular carcinoma (HCC) is essential for successful treatment. Although the role of alpha fetoprotein (AFP) in the diagnosis of advanced HCC is well recognized, at least one third of small HCCs and 15-20% of advanced HCC will be missed unless another diagnostic tool is used. Thus, new serologic markers with sufficient sensitivity and specificity are required. In the present study, we aimed at evaluating the diagnostic and prognostic role of AFP, protein induced by vitamin K absence or antagonist(P1VKA-II), vascular endothelial growth factor (VEGF), sialic acid, alpha-L-fucosidase (AFU) and transforming growth factor-beta 1 (TGF-β1) in the diagnosis and follow up of Egyptian patients with hepatocellular carcinoma in an attempt to find a tumor marker with a reasonable sensitivity and specificity for diagnosis of HCC and monitoring patients after therapy. The study was conducted on 4 selected groups of patients and a control group. Group I included 10 patients with liver cirrhosis. Group II consisted of 10 patients with benign hepatic focal lesions. Group III included 10 HCC patients without distant metastasis and group IV included 10 HCC patients presenting with metastasis. Ten apparently healthy age and sex matched subjects were also included and served as control group. AFP, sialic acid, alpha-L-fucosidase (AFU), VEGF, PIVKA-II and TGF-β1 were determined in the blood of five studied groups. The sensitivity and specificity of the tumor markers were calculated and compared. Significant differences in the median blood levels of AFP, PIVKA-II, VEGF, sialic acid, TGF-β1 and alpha-Lfucosidase activity (AFU) were found on comparing the HCC groups (with and without metastasis) with the other groups. The median blood levels of PIVKA-II, αfetoprotein level, sialic acid and AFU activity were lower in the HCC group without metastasis compared to that with metastasis (p<0.001). On the other hand, the median serum VEGF level was higher in the HCC group without metastasis compared to that of the HCC group with distant metastasis(p<0.001). Serum TGF-β1 level did not vary significantly between both groups (with and without metastasis) (p>0.05). There were significant lower median blood levels of all parameters in HCC patients without metastasis after ablation therapy compared to pretreatment levels. Combined determination of serological markers could be used as a highly valuable tool for screening and diagnosis of HCC as combination of these markers improved their sensitivity and specificity. They could also be used as prognostic markers decreasing the need for more invasive procedures.
Dickkopf-1 and β-catenin as Biomarkers for Early Diagnosis of Hepatocellular Carcinoma
Current Cancer Therapy Reviews, 2020
Background &Aims: The clinical value of alpha-fetoprotein (AFP) as a marker to detect early hepatocellular carcinoma (HCC) has been questioned owing to its low sensitivity and specificity. The purpose of this work was to investigate whether serum Wnt/β-catenin and DKK1 levels in chronic hepatitis C patients could be used as early predictors for the risk of HCC development. Methods: The study was conducted on 37 healthy controls, and 150 CHC patients were divided into three groups: CHC, liver cirrhosis (LC), and HCC patients. AFP, AFP-L3, β-catenin, and DKK-1 were assayed by ELISA. Results: Both β-catenin and DKK1 levels significantly increased (p < 0.001) in the HCC group in comparison to LC and CHC groups. The first cut-off value for DKK-1 was 253 pg/ml with 88% sensitivity and 86% specificity. The second was 301.5 pg/ml with 82 percent sensitivity and 100% specificity. The β-catenin cut-off value was 7.35 ng/ml with 80% sensitivity and 74% specificity. A positive correlation wa...
Cancer, 2014
BACKGROUND: a-Fetoprotein (AFP) is a biomarker commonly used in the management of patients with hepatocellular carcinoma (HCC), although the possible determinants of its serum levels in these patients have not been adequately explored. For this study, the authors evaluated the relevance of demographic, clinical, and oncologic factors to the presence of elevated AFP levels in large cohort of patients with HCC. METHODS: In 4123 patients with HCC who were managed by the Italian Liver Cancer Group, AFP levels were assessed along with their association with demographic, biochemical, clinical, and oncologic characteristics. Patients were subdivided according to the presence of elevated AFP (ie, >10 ng=mL). RESULTS: AFP levels were elevated in 62.4% of patients with HCC. Multivariate logistic regression analysis indicated that being a woman (odds ratio [OR], 1.497; 95% confidence interval [95%CI], 1.250-1.793; P <.0001), the presence of cirrhosis (OR, 1.538; 95% CI, 1.050-2.254; P 5.027), liver disease with viral etiology (OR, 1.900; 95% CI, 1.589-2.272; P <.0001), an elevated alanine aminotransferase level (OR, 1.878; 95% CI, 1.602-2.202; P <.0001), a low albumin level (OR, 1.301; 95% CI, 1.110-1.525; P 5.012), an HCC tumor size >2 cm (OR, 1.346; 95% CI, 1.135-2.596; P 5.001), multinodular HCC (OR, 1.641; 95% CI, 1.403-1.920; P <.0001), and the presence of vascular invasion (OR, 1.774; 95% CI, 1.361-2.311; P <.0001) were associated independently with elevated levels of AFP. Both the median AFP level and the proportion of patients who had elevated levels Original Article increased with decreasing degrees of HCC differentiation (P <.0001). CONCLUSIONS: Sex and features of chronic liver disease were identified as nontumor characteristics that influence serum AFP levels in patients with HCC. These findings should be taken into account as limitations in interpreting the oncologic meaning of this biomarker in clinical practice. Cancer 2014;120:2150-7.
Liver Transplantation and Surgery, 1995
The assessment of new and more sensitive serum markers for hepatocellular carcinoma (HCC) represents a useful contribution to the diagnosis of small liver tumors, still amenable by surgery. We evaluated the efficacy of the tumor markers proposed during recent years for the study of HCC: alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), serum ferritin (SF), tissue polypeptide antigen (TPA), and, finally, the more recently proposed des-gamma-carboxy prothrombin (DCP). Of the 227 patients included in this retrospective study, 111 had HCC, and 85 of these were also cirrhotic. The remaining 116 patients, considered as the control group, included 23 patients with liver metastases from colorectal cancer, 26 with benign hepatic lesions, 20 with tumors other than HCC without hepatic metastases, and 47 with other liver diseases. For each single tumor marker, the sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and Younden index were assessed. epatocellular carcinoma (HCC) is one of the H most common causes of death in the East and, according to recent reports, is becoming more common in the The proven association of HCC with the hepatitis B and C viruses has made it possible to identify an "at-risk' population within which screening programs can be set up, allowing tumors to be identified at an extremely early ~t a g e .~.~ Indeed, identification of HCC in its initial stages is fundamental in the indication of treatment by surgical removal, possible even in the case of patients with compromised liver function5 in whom resection must be carried out with maximum preservation of functional liver parenchyma.6 Current screening programs are based on alpha fetoprotein (AFP) assay and abdominal ultrasound scans (US) .7-9