ArticlePloS one2017
TEMs but not DKK1 could serve as complementary biomarkers for AFP in diagnosing AFP-negative hepatocellular carcinoma.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 3 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 3 syntheses or guidelines pooled it, 19 citations in OpenAlex.
- A meta-analysis and of clinical values of 11 blood biomarkers, such as AFP, DCP, and GP73 for diagnosis of hepatocellular carcinoma.Annals of medicine · 2023Pooled it
- Abdominal ultrasound and alpha-foetoprotein for the diagnosis of hepatocellular carcinoma in adults with chronic liver disease.The Cochrane database of systematic reviews · 2021Pooled it
- Diagnostic accuracy of serum dickkopf-1 protein in diagnosis hepatocellular carcinoma: An updated meta-analysis.Medicine · 2019Pooled it
- Tie2-expressing monocytes/macrophages promote angiogenesis in chronically ischaemic brain tissue.Cell & bioscience · 2025Article
- Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review.International journal of molecular sciences · 2023Review
- Detection of key mRNAs in liver tissue of hepatocellular carcinoma patients based on machine learning and bioinformatics analysis.MethodsX · 2023Article
- Dickkopf-1 Promotes Angiogenesis and is a Biomarker for Hepatic Stem Cell-like Hepatocellular Carcinoma.International journal of molecular sciences · 2022Article
- The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?International journal of biological sciences · 2022Review
- Recipient Hepatic Tumor-Associated Immunologic Infiltrates Predict Outcomes After Liver Transplantation for Hepatocellular Carcinoma.Annals of transplantation · 2020Article
- Des-gamma-carboxyprothrombin is a favorable biomarker for the early diagnosis of alfa-fetoprotein-negative hepatitis B virus-related hepatocellular carcinoma.The Journal of international medical research · 2020Article
- Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma: Origin, Polarization, Function, and Reprogramming.Frontiers in cell and developmental biology · 2020Review
- New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma.Frontiers in oncology · 2020Review
- Chemoprevention of elite tea variety CFT-1 rich in EGCG against chemically induced liver cancer in rats.Food science & nutrition · 2019Article
- HCC with low- and normal-serum alpha-fetoprotein levels.Clinical practice (London, England) · 2018Article
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6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsHepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is prevalent worldwide. Despite its limitations, serum alpha-fetoprotein (AFP) remains the most widely-used biomarker for the diagnosis of HCC. This study aimed to assess whether measurement of peripheral plasma Dickkopf-1 (DKK1) and Tie2-expressing monocytes (TEMs) could overcome the limitations of AFP and improve the diagnostic accuracy of HCC.
methodsPlasma DKK1 level and the percentage of TEMs in peripheral CD14+CD16+ monocytes from HCC patients (n = 82), HBV-related liver cirrhosis (LC) patients (n = 29), chronic hepatitis B (CHB) infected patients (n = 28) and healthy volunteers (n = 31) were analyzed by ELISA and flow cytometry. Receiver operating characteristic (ROC) curves were used to analyze a single biomarker, or a combination of two or three biomarkers. Univariate and multivariate analyses were performed to assess the significance of each marker in prediction of HCC and AFP-negative HCC from LC patients.
resultsThe percentage of TEMs in peripheral CD14+CD16+ monocytes and plasma level of DKK1 in HCC group were significantly higher than those in LC, CHB and healthy control groups (all P-values <0.05). The percentage of TEMs alone was also significantly higher in AFP-negative HCC group than that in LC, CHB and healthy control groups (all P-values <0.05). Plasma DKK1 level alone could not distinguish between AFP-negative HCC and LC patients. ROC curves showed that the optimal diagnostic cutoff value was 550.93 ng/L for DKK1 and 4.95% for TEMs. There was no significant difference in AUC of DKK1, TEMs and AFP in HCC diagnosis between the four groups (all P>0.05). A combination of DKK1, TEMs and AFP measurements increased the AUC for HCC diagnosis as compared with either marker alone (0.833; 95%CI 0.768-0.886). The AUC for TEMs was 0.692 (95% CI 0.564-0.819) in differentiating AFP-negative HCC from LC, with a sensitivity of 80.0% and a specificity of 65.52%. Only TEMs prevailed as a significant predictor for AFP-negative HCC differentiating from LC patients in univariate and multivariate analyses (P = 0.016, P = 0.023).
conclusionsTEMs and DKK1 may prove to be potential complementary biomarkers for AFP in the diagnosis of HCC. TEMs rather than DKK1 could serve as a complementary biomarker for AFP in the differential diagnosis of AFP-negative HCC versus LC patients.
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