Serum Dickkopf-1 as A Biomarker for The Diagnosis and Prognosis of Hepatocellular Carcinoma (original) (raw)

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.

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.

Evaluation of serum dickkopf-1 as a tumor biomarker for diagnosis and prognosis of hepatocellular carcinoma in patients with cirrhotic liver

International journal of advanced research in medicine, 2023

Background: Liver cancer is the fifth most common cancer and the second most frequent cause of cancer-related death globally. Diagnosis of hepatocellular carcinoma (HCC) should occur in an early stage, so that the patient benefits from earlier diagnosis, through treatment using established algorithms. The research aimed to evaluate the significance of Dickkopf-1 (DKK1) as a tumor biomarker for the diagnosis and prognosis of HCC in cirrhotic cases. Methods: This prospective, randomized, controlled research was carried out on 120 individuals who were classified as follow: Group I: comprised 40 cases with cirrhotic liver and HCC. Group II: comprised 30 cases with cirrhotic liver without HCC. Group III: comprised 30 cases with chronic hepatitis without cirrhosis. Control group: comprised 20 healthy individuals. Serum DKK-1 level were measured to all participants but for HCC patient group it was measured before intervention and one month after intervention (with the first CT after intervention). Results: Six cases of group I underwent microwave ablation, 13 cases underwent RFA, 20 cases underwent trans-arterial chemotherapy (TACE) and one patient underwent liver transplantation. Thirteen cases of group I were well ablated following loco regional therapy and no recurrence or de novo lesions appeared during follow up. Residual activity or de novo lesions or recurrence appeared in 26 cases who required second cession of ablation. alpha-fetoprotein (AFP) in group I was ranging between 3.6 to 2400 ng/ml with mean 698.870 ng/ml. It was higher in group I than groups II, III, and IV. DKK1 level was significantly higher in group I than groups II, III and IV, also, was significantly higher in group II than groups III and IV and it was significantly higher in group III than group IV. Conclusions: Serum DKK1 could serve as a potential diagnostic biobiomarker for HCC. DKK1 might be utilised as a predictor of therapeutic ablation outcome in cases with hepatocellular carcinoma.

Serum Dickopff 1 as a Novel Biomarker in Hepatocellular Carcinoma Diagnosis and Follow Up After Ablative Therapy

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.

Usefulness of Highly Sensitive AFP-L3 and DCP in Surveillance for Hepatocellular Carcinoma in Patients with a Normal Alpha-Fetoprotein

Journal of Medical Microbiology & Diagnosis, 2014

Background and aims: Early detection of Hepatocellular Carcinoma (HCC) is crucial for effective management. Incidence of HCC has increased in the United States largely attributed to hepatitis B and C virus. Lens culinaris agglutinin-reactive Alpha-Fetoprotein (AFP-L3) and Des-Gamma-Carboxy Prothrombin (DCP) are being recognized specific biomarkers for HCC. Methods: We measured AFP-L3 and DCP in serial serum specimens of a cohort of chronic hepatitis patients on HCC surveillance and compared these markers to abdominal imaging. Among fifty patients who developed HCC during surveillance, 30 were included in the study with available sera 1-2 years before, at diagnosis and post ablation of HCC. For controls, three consecutive annual sera were examined from 106 chronic hepatitis patients without HCC during surveillance for 5-10 years. The µTASWako i30 auto analyzer was used for the assay that utilizes the microfluidics chip based assay platform. It can fractionate AFP-L3 glycoform and calculates AFP-L3% if AFP level is ≥ 0.6 ng/mL. Results: Combination of AFP, AFP-L3 and DCP showed high sensitivity of 83% in all patients and 75% in patients with AFP<20 ng/mL. AFP-L3 and DCP assays were useful in patients with low levels of AFP (<20 ng/mL) and could detect significant AFP-L3% elevation in some patients more than one year before the diagnosis of HCC. Furthermore, AFP-L3 predicted recurrence of HCC. Conclusions: This is the first study in the U.S. patients using the µTASWako i30 analyzer to test these HCC biomarkers. Our results suggest that combinations of these biomarkers are highly useful for early detection of HCC.

Assessment of alpha-fetoprotein clinical performances in the diagnosis of hepatocellular carcinoma at Sominé DOLO Hospital of Mopti

International Journal of Clinical Biochemistry and Research, 2023

Background: Serum AFP has a poor clinical performance values especially when it comes to dealing with the early and AFP-negative diagnostic of HCC. This study aimed to assess the contribution of AFP in the diagnosis of HCC. Materials and Methods: A total of 95 subjects were in a prospective observational study by consecutive enrolment and divided into two groups. The first group was made up with subjects in whom the diagnosis of HCC had been retained the second was the control group which was free of HCC. AFP levels were performed by electrochemiluminescence immunoassay on the cobas e411®. Data were captured in Excel and analyzed by Ri386 version 4.1.2 binary for macOS 10.13. Results: Log of AFP median of AFP in HCC subjects was significantly greater than in non HCC subjects 6.91 ng/mL versus 1.43 ng/mL, Wilcoxon p-value < 0.001. At the cutoff of 200 ng/mL, the clinical performances showed an acceptable sensitivity 97.1% CI 95% [93.7-100] but a poor specificity 73,8% CI 95% [64.9-82.6] and out of the 34 cases of HCC, one case (2.9%) was AFP-negative HCC. Conclusion: Our data show an acceptable sensitivity but a weak specificity of AFP as a biomarker for HCC at a cutoff 200 ng/mL. This suggests that AFP should be used with other biomarkers, mainly for the early and AFP-negative HCC diagnosis. This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

Alpha-Fetoprotein, Alpha-Fetoprotein-L3, Protein Induced by Vitamin K Absence, Glypican 3 and Its Combinations for Diagnosis of Hepatocellular Carcinoma

Surgery, Gastroenterology and Oncology

Introduction: Despite its limitations, alpha-fetoprotein (AFP) is still the most common used serum marker for hepatocellular carcinoma (HCC). Alpha-fetoprotein-L3 (AFP-L3), protein induced by vitamin K absence (PIVKA-II) and Glypican-3 (GPC-3) have been proposed as complementary biomarkers but their role is still controversial. Aims and Methods: We prospectively included 101 patients with HCC and 52 control patients with liver cirrhosis with the aim to investigate the diagnostic performance of AFP, AFP-L3 PIVKA-II, and GPC-3 as single markers or in combination for HCC diagnosis. To compare the diagnostic value in distinguishing the presence of HCC from chronic nonmalignant liver disease, receiver operating characteristic (ROC) curves were constructed for each marker and for every combination of markers. Results: When all biomarkers were individually analyzed, AFP-L3 had the highest area under the curve (AUC) (0.84), followed by AFP (0.79), PIVKA-II (0.75) and GPC-3 (0.73) for HCC diagnosis. The best sensitivity (84.7%) was for AFP L3 at a cutoff >13.5ng/mL and the best specificity (93.9%) was for AFP at a cutoff >18.9 ng/mL. For combinations of two biomarkers, the AUC was highest (0.87) for AFP and AFP-L3. The combination of all four biomarkers resulted in a much better sensitivity (88.1%) and specificity (93.9%) than each of the markers individually (p = 0.01). Conclusion: AFP-L3 was the most useful single marker for HCC diagnosis, and the combination of AFP, AFP-L3 and PIVKA-II could maximize the diagnostic performance. Efforts to seek novel combination of biomarkers for HCC should be continued.

Alpha1-acid glycoprotein as potential biomarker for alpha-fetoprotein-low hepatocellular carcinoma

BMC Research Notes, 2010

The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of late diagnosis. We determined the performances of α -1-acid glycoprotein (AAG) and des-γ-carboxy prothrombin (DCP) for the diagnosis of HCC, especially for α-fetoprotein (AFP)-low HCC. Methods: Of the 220 patients included in this retrospective study, 124 had HCC, and 61 (49%) of these were AFPlow HCC (AFP ≤ 20 ng/mL). The remaining 96 patients, including 49 with chronic hepatitis B or C and 47 with cirrhosis, were considered as control. Plasma AAG was analyzed using high performance liquid chromatography (HPLC) and confirmed using Western blot technique. Results: When all patients with HCC were evaluated, the area under receiver operating characteristic (ROC) curves for AAG (0.94, 95% CI: 0.91-0.97) and DCP (0.92, 95% CI: 0.88-0.95) were similar (P = 0.40). AAG had better area under ROC curve (0.96, 95% CI: 0.94-0.99) than DCP (0.87, 95% CI: 0.81-0.93) for AFP-low HCC (P < 0.05). At the specificity 95%, the sensitivity of AAG was higher in AFP-low HCC than in AFP-high HCC (82% and 62%, respectively). In contrast, higher sensitivity was obtained from DCP in discriminating HCC patients with low AFP than that in high AFP (57% and 90%, respectively). Conclusion: Our cross-sectional study showed that AAG was better performance in diagnosing HCC patients with low AFP, while DCP did better in those with high AFP.