Golgi protein 73 versus alpha-fetoprotein as a biomarker for hepatocellular carcinoma: a diagnostic meta-analysis.
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ABSTRACT:
SUBMITTER: Zhou Y
PROVIDER: S-EPMC3292967 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundScreening of early hepatocellular carcinoma (HCC) diagnosis is the greatest challenge for hepatologists. Alpha?-fetoprotein (AFP) is the most common non-invasive biomarker used in HCC diagnosis.Objectives and AimsTo make a comparison between the new biomarker Golgi protein 73 (GP73) versus the standard biomarker AFP in the diagnosis of HCC.MethodsOur study was a case–control study, and 60 patients were included in the study. They were divided into two groups: ?1) HCC patients with either chronic HBV or HCV infection (n=30); and ?2) ?non-HCC patients with HBV or HCV infection who had either chronic hepatitis or liver cirrhosis (n=30). In addition, 30 healthy volunteers were included as a control group. Patients were subjected to liver function tests, kidney function tests, serum Golgi protein 73 and AFP levels. Imaging diagnosis of HCC was done by ?computed ?tomography (CT) or ?magnetic ?resonance ?imaging (MRI) based on American Association for the Study of Liver Diseases (AASLD) ?practice ?guidelines.ResultsStatistically significant differences between groups in terms of serum AFP (p<0.001) and GP73 (p<0.001) were found. Non-HCC patients (chronic hepatitis and liver cirrhosis) and HCC patients had significantly higher AFP and GP73 than the control group. In addition, patients with HCC had significantly higher AFP and GP73 than chronic hepatitis and cirrhotic patients. GP73 had higher diagnostic performance than AFP. At a cut-off value of ?8.4 ng/mL, GP73 yielded a sensitivity of 86.7% and specificity of 89% for the discrimination between HCC and normal populations. Similarly, at a cut-off value of ?8.45 ng/mL, GP73 yielded a sensitivity of 83.3% and specificity of 84% for the discrimination between HCC patients and non?-HCC patients. On the other hand, AFP at a cut-off value of ?2.4 ng/mL yielded a sensitivity of 75.4% and specificity of 90% for the discrimination between HCC and normal populations?; and at a cut-off value of ?20.85 ng/mL, AFP yielded a sensitivity of 72.2% and specificity of 86.2% for the discrimination between HCC and non-HCC patients.ConclusionGolgi protein 73 is a promising and accurate biomarker for early detection of HCC.
| S-EPMC7244238 | biostudies-literature
Project description:Conflicting results have been widely reported on the use of Golgi protein 73 (GP73) as a serum biomarker for diagnosing hepatocellular carcinoma (HCC). This study evaluated the accuracy of GP73, alpha-fetoprotein (AFP), and GP73 + AFP for diagnosing HCC. The meta-analysis was performed on 11 studies that were selected by means of a comprehensive systematic literature review. Summary diagnostic accuracy, meta-regression analysis for heterogeneity and publication bias, and other statistical analyses were performed using Meta-Disc (version 1.4) and Stata (version 12.0). Pooled sensitivity, specificity, and diagnostic odds ratio were 0.77 (95% CI: 0.75-0.79), 0.91 (95% CI: 0.90-0.92), and 12.49 (95% CI: 4.91-31.79) for GP73; 0.62 (95% CI: 0.60-0.64), 0.84 (95% CI: 0.83-0.85), and 11.61 (95% CI: 8.02-16.81) for AFP; and 0.87 (95% CI: 0.85-0.89), 0.85 (95% CI: 0.84-0.86), and 30.63 (95% CI: 18.10-51.84) for GP73 + AFP. The area under the curve values were 0.86, 0.84, and 0.91 for GP73, AFP, and GP73 + AFP, respectively. These results indicate that for HCC diagnosis, the accuracy of GP73 was higher than that of AFP, and that GP73 + AFP exhibited significantly higher diagnostic accuracy than did GP73 or AFP alone.
| S-EPMC4595485 | biostudies-literature
Project description:BackgroundAlpha-fetoprotein (AFP) has been extensively applied in clinical practice to detect and predict postoperative outcomes of patients with hepatocellular carcinoma (HCC). However, due to its low sensitivity and specificity, its efficacy has been questioned. Recently, novel serum biomarkers including Golgi protein 73 (GP73) and glypican-3 (GPC-3) have shown a better discriminatory ability than AFP in detecting early HCC. The results of the combined use of GP73, GPC-3 and AFP in the diagnosis of HCC remain inconclusive. This investigation aimed to evaluate the discriminatory ability of GP73, GPC-3 and AFP to jointly identify HCC using the statistical methods of meta-analysis.MethodsComprehensive database searches of, Web of Science, the Cochrane Library, Embase, the Chinese Biomedical Literature Database, and the China National Knowledge Infrastructure were performed for literature dated up to 1 November, 2019. Studies relating to the diagnostic accuracy of the combination of GP73, GPC-3 and AFP in the identification of HCC were included. A random-effects model was used to pool sensitivity, specificity, the positive and negative likelihood ratios [positive likelihood ratio (PLR) and negative likelihood ratio (NLR), respectively], and the diagnostic odds ratio (DOR). We applied the Fagan nomogram to assess the clinical utility of joint detection. The overall detection accuracy was determined using summary receiver operating characteristic curve (SROC) analysis. Meta-regression analysis of heterogeneity publication bias was analyzed with Stata (version 12.0).ResultsOur meta-analysis focused on 12 studies involving 919 patients with HCC and 1,549 non-HCC patients. Sensitivity, specificity, PLR, NLR and DOR for joint detection, were 0.91 (95% CI: 0.87-0.94), 0.84 (95% CI: 0.77-0.89), 5.83 (95% CI: 4.05-8.40), 0.10 (95% CI: 0.07-0.15), 57.51 (95% CI: 35.92-92.08), respectively, when pooled, and the area under the SROC curve was 0.95.ConclusionsCurrent evidence indicates that GP73, GPC-3 and AFP exhibit much better accuracy for the diagnosis of HCC when used in combination rather than alone or in pairs.
| S-EPMC7214882 | biostudies-literature
Project description:Golgi protein 73 (GP73), a resident protein of the Golgi apparatus, is notably elevated in hepatocellular carcinoma (HCC). While its critical role in remodeling the tumor microenvironment (TME) is recognized, the intricate mechanisms are not fully understood. This study reveals that GP73 in HCC cells interacts with prolyl hydroxylase-2 (PHD-2) in a competitive manner, thereby impeding the hydroxylation of hypoxia-induced factor-1α (HIF-1α). The effect above promotes the production and secretion of vascular endothelial growth factor A (VEGFA). Moreover, exosomal GP73 derived from HCC cells can be internalized by human umbilical vein endothelial cells (HUVECs) and competitively interact with HECTD1, an E3 ubiquitin ligase targeting growth factor receptor-bound protein 2 (GRB2). This interaction stabilizes GRB2, thereby activating the Ras-mitogen-activated protein kinase (MAPK) signaling pathway. Consequently, escalated levels of GP73 intensify VEGF production in HCC cells and potentiate mitogenic signaling in vascular endothelial cells, fostering angiogenesis in the TME. Our findings propose that GP73 might serve as a novel target for anti-angiogenic therapy in HCC.
| S-EPMC11251733 | biostudies-literature
Project description:Golgi-protein 73 (GP73) is highly expressed in hepatocellular carcinoma (HCC) and, as a secretory protein, it has been proposed as a serum biomarker indicating progression of HCC. The underlying mechanism by which GP73 may promote HCC metastasis is still poorly understood. In this study, we discovered that GP73 interacted with vimentin to facilitate Serine/Threonine-protein phosphatase PP1-alpha (PP1A)-mediated dephosphorylation of vimentin at S56 and facilitated vimentin polymerization, which blocked vimentin degradation via TRIM56-mediated ubiquitin/proteasome-dependent pathway. Strikingly, Clomipramine, a 5-hydroxytryptamine receptor (5-HTR) agonist approved for the treatment of depression, impaired GP73-mediated vimentin polymerization to effectively inhibit metastasis of HCC with high GP73 expression, which provided a new strategy against HCC metastasis. Lastly, it was found that serum GP73 (sGP73) correlated positively with vimentin in primary tissues of HCC, suggesting that sGP73 might serve as a potential serum biomarker for companion diagnosis of HCC with highly expressed vimentin. In summary, this study reveals the process of GP73-mediated vimentin polymerization and proves that Clomipramine serves as a potential drug targeting vimentin for metastatic HCC patients with high sGP73 level.
| S-EPMC10411459 | biostudies-literature
Project description:Exosomal microRNAs have recently been studied as the potential diagnostic marker for various malignancies, including hepatocellular carcinoma (HCC). The aim of this study was to investigate serum exosomal microRNA profiles as HCC diagnostic marker. Transmission electron microscopy and Western blot were used to identify serum exosomes. Deep sequencing was performed to screen differentially expressed microRNAs between HCC (n = 5) and liver cirrhosis (LC, n = 5) groups. Three upregulated and two downregulated microRNAs were selected for qPCR analysis. The levels of selected microRNAs were normalized to Caenorhabditis elegans miR-39 microRNA mimics. Serum exosomal level of miR-122, miR-148a, and miR-1246 was further analyzed and significantly higher in HCC than LC and normal control (NC) groups (P < 0.001), but not different from chronic hepatitis group (P > 0.05). The receiver operating characteristic curve was used to evaluate the diagnostic performance of candidate microRNAs. Area under the curve (AUC) of miR-148a was 0.891 [95% confidence interval (CI), 0.809-0.947] in discriminating HCC from LC, remarkably higher than alpha-fetoprotein (AFP) (AUC: 0.712, 95% CI: 0.607-0.803). Binary logistic regression was adopted to establish the diagnostic model for discriminating HCC from LC. And the combination of miR-122, miR-148a, and AFP increased the AUC to 0.931 (95% CI, 0.857-0.973), which can also be applied for distinguishing early HCC from LC. miR-122 was the best for differentiating HCC from NC (AUC: 0.990, 95% CI, 0.945-1.000). These data suggest that serum exosomal microRNAs signature or their combination with traditional biomarker may be used as a suitable peripheral screening tool for HCC.
| S-EPMC5943469 | biostudies-literature
Project description:PurposeAtezolizumab + bevacizumab is the new standard of care for systemic treatment-naïve, unresectable hepatocellular carcinoma (HCC). This exploratory study investigated on-treatment alpha-fetoprotein (AFP) response as a potential surrogate biomarker of prognosis for the combination therapy.Experimental designData from Group A of the phase Ib GO30140 study were used to identify the optimal time for AFP measurement and AFP cutoffs to differentiate patients by their best confirmed response per independent review facility-assessed RECIST (IRF-RECIST) version 1.1: responders from nonresponders and patients with disease control from primary progressors. We applied these cutoffs to independent data from the atezolizumab + bevacizumab arm of the phase III IMbrave150 trial to distinguish patients based on (i) overall survival (OS) and progression-free survival (PFS) per IRF-RECIST 1.1 and (ii) best confirmed response per IRF-RECIST 1.1.ResultsWe derived AFP cutoffs of ≥75% decrease and ≤10% increase from baseline at 6 weeks to identify responders and those who had disease control, respectively. These cutoffs had high sensitivity and specificity in GO30140. In IMbrave150 patients, sensitivity was 0.59 and specificity was 0.86 for the ≥75% decrease AFP cutoff; the sensitivity was 0.77 and specificity was 0.44 for the ≤10% increase AFP cutoff. Both AFP cutoffs were associated with longer OS and PFS, particularly in patients with hepatitis B virus etiology (HR < 0.5; P < 0.01).ConclusionsAFP response at 6 weeks after initiating treatment is a potential surrogate biomarker of prognosis for patients with HCC receiving atezolizumab + bevacizumab. See related commentary by Cappuyns and Llovet, p. 3405.
| S-EPMC9662926 | biostudies-literature
Project description:The biomarkers α-fetoprotein (AFP), Lens culinaris agglutinin-reactive AFP fraction (AFP-L3), and des-γ-carboxy prothrombin (DCP) have emerging implications in hepatocellular carcinoma (HCC) surveillance, overall prognosis, and post-surgical recurrence risk. This retrospective study investigated treatment and bridge to liver transplant (LT) prognosis associated with AFP, AFP-L3%, and DCP biomarker profiles prior to liver-directed therapy (LDT). In a 140-patient cohort, each biomarker was associated with HCC progression risk using the established thresholds of AFP > 20 ng/mL, AFP-L3 > 15%, and DCP > 7.5 ng/mL. Over 60% of the cohort expressed at least one biomarker at baseline. Although most biomarker-positive patients expressed the clinical standard AFP (57/87), only 32% were positive for AFP alone. Biomarker accumulation increased HCC progression risk but was not associated with demographic factors or preserved liver function. Biomarker triple negative patients had smaller index HCC (p = 0.003), decreased multifocal burden (p = 0.010), and a higher objective response rate (ORR, 62% compared to 46%, p = 0.011). Expressing all three biomarkers at baseline was associated with dismal first-line ORR (12%) with a median time to progression (TTP) of only 181 days post-LDT. Patients with triple negative status for the HCC biomarkers AFP, AFP-L3%, and DCP have the highest first-line ORR with < 5% HCC progression 1-year post-LDT. Biomarker profiling can establish baseline prognosis for identifying optimal bridge to LT and downstaging to LT candidates with triple negative biomarker status and providing an ideal post-LDT target as a compliment to radiographic response.
| S-EPMC8507524 | biostudies-literature
Project description:BackgroundThe clinical value of alpha-fetoprotein (AFP) in patients with AFP-negative (< 20 ng/ml) hepatocellular carcinoma (HCC) who underwent curative resection remained controversial.AimsTo investigate clinical relevance and prognostic effect of preoperative serum AFP level in this subgroup.MethodsA total of 1879 patients with AFP-negative HCC who underwent curative resection were included in the study. Overall survival (OS) and disease-free survival (DFS) rate were displayed by Kaplan-Meier method and compared by log-rank test. Multivariate cox proportional hazard regression analysis was used to identify the independent prognostic factors. The prognostic predictive performance was analyzed by time-dependent areas under receiver operating characteristic curve (AUC).ResultsEven in AFP-negative HCC, patients with high preoperative serum AFP level tended to have multiple tumor (P < 0.001), poorer differentiation of tumor cell (P < 0.001), presence of satellite nodules (P < 0.001), and MVI (P = 0.002). Kaplan-Meier analysis showed the adverse impact of AFP level on prognosis, especially for DFS. Multivariate analysis identified AFP as the independent unfavorable factor for OS and DFS (P < 0.001 for both). Time-dependent AUC analysis showed that the combination with AFP could improve the prognostic predictive performance of 8th AJCC and BCLC staging system.ConclusionsAFP was still the surrogate of aggressive behavior of HCC and independent prognostic factor for patients with AFP-negative HCC underwent curative resection. Even combining with such a low level of AFP could significantly improve the predictive performance of conventional staging system.
| S-EPMC8589766 | biostudies-literature
Project description:The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration > 400 ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab. Those AFP-high tumours (18% of resected cases) were characterised by significantly lower AFP promoter methylation (p < 0.001), significant enrichment of progenitor-cell features (CK19, EPCAM), higher incidence of BAP1 oncogene mutations (8.5% vs 1.6%) and lower mutational rates of CTNNB1 (14% vs 30%). Specifically, AFP-high tumours displayed significant activation of VEGF signalling (p < 0.001), which might provide the rationale for the reported benefit of ramucirumab in this subgroup of patients.
| S-EPMC6738090 | biostudies-literature