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

2013 ◽  
Vol 28 (3) ◽  
pp. 286-297 ◽  
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.

scholarly journals Low Serum Melatonin Levels Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma are Associated with Lower Survival after Liver Transplantation

2019 ◽  
Vol 20 (7) ◽  
pp. 1696
Author(s):  
Leonardo Lorente ◽  
Sergio Rodriguez ◽  
Pablo Sanz ◽  
Pedro Abreu-González ◽  
Agustín González-Rivero ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Antioxidant Capacity ◽  
Total Antioxidant Capacity ◽  
Serum Levels ◽  
High Serum ◽  
Published Data ◽  
Lower Serum ◽  
Total Antioxidant ◽  
One Year

Melatonin administration has been associated with different benefits in animals and patients suffering from liver diseases. However, there is no published data about circulating melatonin levels in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT). Thus, the objective of this observational and retrospective study was to determine whether patients with HCC with lower serum melatonin levels prior to LT have a higher risk of one-year mortality after LT. We measured serum levels of melatonin, malondialdehyde (to assess lipid peroxidation), and total antioxidant capacity (to assess antioxidant state) before LT. One-year surviving LT patients (n = 129) showed higher serum levels of melatonin (p = 0.001) and total antioxidant capacity (p = 0.001) and lower serum levels of malondialheyde (p = 0.01) than non-surviving LT patients (n = 16). Logistic regression analysis showed that high serum melatonin levels prior to LT were associated with lower one-year LT mortality (odds ratio = 0.525; 95% confidence interval (CI) = 0.331–0.834; p = 0.006). We found an association between serum levels of melatonin with serum levels of malondialheyde (rho = −0.22; p = 0.01) and total antioxidant capacity (rho = 0.21; p = 0.01). Thus, the novel findings of our study were the association between high serum melatonin levels prior to LT and survival at first year after LT and the association between serum levels of melatonin with malondialheyde and total antioxidant capacity.

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

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 321 ◽  
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.

scholarly journals Elevated Preoperative Serum CA19-9 Levels in Patients with Hepatocellular Carcinoma Is Associated with Poor Prognosis after Resection

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yu-Ling Chen ◽  
Chien-Hung Chen ◽  
Rey-Heng Hu ◽  
Ming-Chih Ho ◽  
Yung-Ming Jeng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Poor Prognosis ◽  
Characteristic Curve ◽  
Tumor Grade ◽  
Serum Levels ◽  
Tumor Stage ◽  
High Serum ◽  
Term Survival ◽  
Preoperative Serum

Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status,α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC.

Serum levels of macrophage inhibitory cytokine-1 (MIC1) and matrix metallopeptidase-7 (MMP7) as diagnostic and prognostic markers in gastric cancer (GC) patients (pts).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14595-e14595
Author(s):  
Manuel Valladares-Ayerbes ◽  
Nuria Tarrío ◽  
Moisés Blanco-Calvo ◽  
Mar Haz-Conde ◽  
Isabel Santamarina Cainzos ◽  
...  
Keyword(s):  
Diagnostic Performance ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Serum Levels ◽  
High Serum ◽  
Youden Index ◽  
Matrix Remodeling ◽  
Diagnostic Potential ◽  
Increased Risk

e14595 Background: MIC1 and MMP7 are secreted cytokines involved respectively in the modulation of immunological processes and in extracellular matrix remodeling. Their expression were found deregulated in different tumors, including GC. However, few data are available about their serum levels, their diagnostic potential, and their prognostic significance in GC pts. Here, we analyze the diagnostic performance of these markers and we present data linking them with short survival in GC pts. Methods: Serum samples were assayed in duplicate for MIC1 and MMP7 levels by ELISA. The diagnostic performance of markers was assessed by ROC curve analysis and the cut-offs were set using the Youden index approach. The cut-offs for prognostic purposes were determined using X-tile software. Differences in progression free (PFS) and overall survival (OS) were analyzed using Kaplan-Meier curves and logrank test. Cox regression was used to determine the prognostic independence of biomarkers. Results: From November 2006 to July 2010, 52 GC pts and 28 healthy donors were consecutively recruited. The follow-up of pts was performed until their death or the end of study (September 2011). The AUCs for MIC1 and MMP7 were respectively 0.897 and 0.865 (p < 0.001). Using the optimal cut-off to diagnose GC pts, we obtained a 73.08% of sensitivity (Ss) and a 92.86% of specificity (Sp) for MIC1, and a 78.85% of Ss and an 85.71% of Sp for MMP7. In the survival analysis, high serum levels of MIC1 and MMP7 were significantly associated with shorter PFS (p < 0.001) and OS (p < 0.001 and p = 0.003, respectively). In univariate analysis, pts with high serum levels of MIC1 and MMP7 had an increased risk of progression (HR = 3.608, p<0.001 for MIC1; HR = 4.172, p<0.001 for MMP7) and death (HR = 3.843, p=0.001 for MIC1; HR = 2.602, p=0.006 for MMP7). However, MIC1 and MMP7 failed to reach prognostic independence in multivariate analysis. Conclusions: We obtained cut-off values of MIC1 and MMP7 in serum for diagnostic purposes in GC. In addition, we established a correlation between increased levels of MIC1 and MMP7 in serum and shorter PFS and OS in GC. These findings justify studies with a larger number of pts.

High serum levels of sclerostin and Dickkopf-1 are associated with acute ischaemic stroke

2016 ◽  
Vol 253 ◽  
pp. 22-28 ◽  
Author(s):  
Xin-Wei He ◽  
En Wang ◽  
Yu-Yan Bao ◽  
Feng Wang ◽  
Ming Zhu ◽  
...  
Keyword(s):  
Ischaemic Stroke ◽  
Acute Ischaemic Stroke ◽  
Serum Levels ◽  
High Serum ◽  
Dickkopf 1

scholarly journals An inflammatory cytokine signature helps predict COVID-19 severity and death

2020 ◽  
Author(s):  
Diane Marie Del Valle ◽  
Seunghee Kim-schulze ◽  
Huang Hsin-hui ◽  
Noam D Beckmann ◽  
Sharon Nirenberg ◽  
...  
Keyword(s):  
New York ◽  
Disease Severity ◽  
Cox Regression ◽  
Predictive Biomarkers ◽  
Clinical Information ◽  
Serum Levels ◽  
The United States ◽  
High Serum ◽  
Laboratory Test Results ◽  
Tnf Α

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

scholarly journals High Serum Levels of Cholesterol Increase Antitumor Functions of Nature Killer Cells and Reduce Growth of Liver Tumors in Mice

2020 ◽  
Vol 158 (6) ◽  
pp. 1713-1727 ◽  
Author(s):  
Wen-Hao Qin ◽  
Zhi-Shi Yang ◽  
Mian Li ◽  
Yao Chen ◽  
Xiao-Fang Zhao ◽  
...  
Keyword(s):  
Liver Tumors ◽  
Serum Levels ◽  
High Serum ◽  
Killer Cells

Serum Dickkopf-1 as a diagnostic & prognostic marker for Hepatocellular Carcinoma

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Enas Mahmoud Foda ◽  
Khaled Amr Mansour ◽  
Walaa Mohamed Hashem ◽  
Nancy Zakaria Ali
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Prognostic Marker ◽  
Early Stage ◽  
Serum Levels ◽  
University Hospitals ◽  
Post Intervention ◽  
Curative Therapy ◽  
Diagnostic Role ◽  
Dickkopf 1

Abstract Background Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the second leading reason of cancer-associated deaths around the world.The poor outcome of patients with HCC is attributed to late detection, with more than two-thirds of patients diagnosed at advanced stages of the disease. However, a considerable improvement in survival has been observed (5-year survival up from 40% to 70%) when patients are diagnosed at an early stage and receive potentially curative therapy in the form of liver transplantation, surgical resection, or tumor ablation. Objective Evaluate levels of serum Dickkopf-1, & its significance as a diagnostic & prognostic marker for Hepatocellular Carcinoma. Aim of the work assess the possible diagnostic role of serum DKK1 compared to alpha- fetoprotein which is the slandered marker used for diagnosis of HCC.also DKK1 act as prognostic marker for Hepatocellular Carcinoma. Pateints and Methodes This study had been carried out on 45 subjects diveded into 2 groups,first group include 30 pateints with liver cirrhosis,and second group 15 pateints with HCC.In this group of patients DKK1 was withdrawn before TACE & 3 months post intervention, age range 25-73 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from March 2019 till January 2020.They were distributed as 25 males and 20 females. There were 13 pateints with child A,17 pateints with child B, & 15 pateints (20%) with child C. Results In this study, the serum levels of serum DKK1 were highest in patients with HCC compared to those with liver cirrhosis. Also DKK1 values significally decreased after intervention(TACE). Conclusion Serum DKK1 act as a diagnostic marker for HCC and its level significally decrease after TACE

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