Dataset Information

Development of a Chemiluminescence Immunoassay for Serum YB-1 and its Clinical Application as a Potential Diagnostic Marker for Hepatocellular Carcinoma.

ABSTRACT: BACKGROUND:Y-box binding protein 1 (YB-1) overexpression has been shown in various tumor cells including hepatocellular carcinoma (HCC); moreover, this protein can be actively secreted. OBJECTIVES:The aim of this study was to establish a method to quantify serum YB-1 and evaluate its clinical application in the clinical diagnosis of HCC. PATIENTS AND METHODS:Recombinant YB-1 and two populations of its antibodies were prepared. A monoclonal antibody was specific to the N-terminus of YB-1 amino acids 134-160; and another was a polyclonal antibody. A sandwich-type chemiluminescence immunoassay (CLIA) was developed and evaluated. Levels of YB-1 and alpha fetoprotein (AFP) in serum samples from 105 HCC patients, 25 hepatitis B virus patients, 25 cirrhosis patients, and 50 healthy donors were detected using the established method and an AFP electrochemiluminescence kit. RESULTS:The developed method was linear to 150 ?g/L of YB-1 with a minimum detection limit of 0.01 ?g/L. The average recoveries were between 93.9% and 109.0%. The mean intra- and inter-assay coefficients of variation (CVs) were 4.0-4.8% and 8.2-10.2%, respectively. The relationship between the concentration of diluted YB-1 and the dilution ratios gave a good linear correlation coefficient of 0.9986. The YB-1 concentration was increased in serum of HCC patients (33.0 ± 23.39 ?g/L) compared to healthy individuals (13.2 ± 5.29 ?g/L, P < 0.0001), patients with HBV (17.9 ± 7.49 ?g/L, P = 0.0003), and patients with HBV cirrhosis (20.7 ± 8.75 ?g/L, P < 0.05). Moreover, the combination of YB-1 and alpha-fetoprotein had a high sensitivity (89.5%) and reasonable specificity (62.0%) in identifying HCC. CONCLUSIONS:The established method has an acceptable performance in quantifying YB-1. In addition, serum YB-1 may aid in the diagnosis of HCC.

SUBMITTER: Pu L

PROVIDER: S-EPMC3782250 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Development of a Chemiluminescence Immunoassay for Serum YB-1 and its Clinical Application as a Potential Diagnostic Marker for Hepatocellular Carcinoma.

Pu Li L Jing Shi S Bianqin Guo G Ping Liu L Qindong Liang L Chenggui Liu L Feng Cheng C Wenbin Kuang K Qin Wang W Jinyu Dong D Qianfeng Xia X Yu Liu L Zhiguang Tu T

Hepatitis monthly 20130703 7

<h4>Background</h4>Y-box binding protein 1 (YB-1) overexpression has been shown in various tumor cells including hepatocellular carcinoma (HCC); moreover, this protein can be actively secreted.<h4>Objectives</h4>The aim of this study was to establish a method to quantify serum YB-1 and evaluate its clinical application in the clinical diagnosis of HCC.<h4>Patients and methods</h4>Recombinant YB-1 and two populations of its antibodies were prepared. A monoclonal antibody was specific to the N-ter ...[more]

PMID: 24069038

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Project description:In cancer management, early and accurate diagnosis of hepatocellular carcinoma (HCC) is important for enhancing survival rate of patients. Currently, serum alpha-fetoprotein (AFP) is the only one biomarker for detection of HCC. However, serum AFP is not satisfactory for diagnosis of HCC due to its low accuracy (about 60-70%). In this study, we collected 109 serum samples (discovery set) from healthy control (HC) and patients with chronic hepatitis B (CHB), liver cirrhosis (LC) and HCC, and analyzed them with custom lncRNA microarray. Profiling analysis shows 181 differentially expressed lncRNAs between HCs and patients with CHB, LC and HCC. Then a 48-lncRNA diagnostic signature was identified with 100% predictive accuracy for all subjects in the discovery set. This diagnostic signature was verified with a cross-validation analysis in the discovery set. To further corroborate the signature, we gathered another 66 serum samples (validation set) and also analyzed them with microarray. The result indicates that the same signature has similar diagnostic accuracy for HC (100%), CHB (73%), LC (88%) and HCC (95%), implying a reproducible diagnostic biomarker for HCC. Receiver operating characteristic (ROC) analysis exhibits that this signature has significantly higher diagnostic accuracy for HCC and non-cancerous subjects (area under curve [AUC]: 0.994) than AFP (AUC: 0.773) in the discovery set and this was also verified in the validation set (0.964 vs 0.792). More importantly, the signature detected small HCC (<3cm) with 100% (13/13) accuracy while AFP with only 61.5% (8/13). Altogether, this study demonstrates that the serum 48-lncRNA signature is not only a powerful and sensitive biomarker for diagnosis of HCC but also a potential biomarker for LC. ***************************************************************** Submitter declares these data are subject to patent number ZL 2016 1 0397094. *****************************************************************

Project description:BackgroundHepatocellular carcinoma (HCC) is a tumor with a high recurrence rate, poor prognosis, and rapid progression. Therefore, it is necessary to find a novel biomarker for HCC. Coiled-coil domain containing 25 (CCDC25) has been identified as a target molecule that mediates liver metastasis in colon cancer. However, the molecular mechanisms of CCDC25 in HCC are unknown. This study aimed to explore the role of CCDC25 in HCC.MethodsThe expression of CCDC25 in HCC was identified through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic curve (ROC) curves were drawn to evaluate the diagnostic value of CCDC25 for HCC. The effect of CCDC25 on the prognosis of HCC was analyzed by using the Kaplan-Meier plotter. Co-expressed genes and Gene Set Enrichment Analysis (GSEA) were used to explore the related functions and regulatory signaling pathways of CCDC25. Moreover, we employed the Tumor Immune Estimation Resource (TIMER) database and CIBERSORT algorithm to investigate the relationship between CCDC25 and the tumor immune microenvironment (TME) in HCC. Meanwhile, the effect of CCDC25 on the sensitivity of HCC patients to chemotherapy drugs was evaluated. Finally, we explored the prognostic methylation sites of CCDC25 using the MethSurv database.ResultsCCDC25 expression was low in HCC. Low CCDC25 expression was significantly associated with poor overall survival of HCC and may be comparable to the ability of AFP to diagnose HCC. Dysregulation of glucose metabolism, fatty acid metabolism, amino acid metabolism, ubiquitination modification, and apoptosis inhibition caused by CCDC25 downregulation may be the causes and results of HCC. In addition, CCDC25 was positively correlated with the infiltration level of various adaptive antitumor immune cells. The levels of immune cell infiltration and immune checkpoint expression were lower in the samples with high CCDC25 expression. What is more, we found that downregulated CCDC25 may increase the sensitivity or resistance of HCC patients to multiple drugs, including sorafenib. We also identified a methylation site for CCDC25, which may be responsible for poor prognosis and low CCDC25 expression in HCC patients. Finally, CCDC25 may be associated with HCC ferroptosis.ConclusionsCCDC25 may be a potential diagnostic and prognostic marker for HCC and is associated with immune infiltration and ferroptosis.

Dataset Information

Development of a Chemiluminescence Immunoassay for Serum YB-1 and its Clinical Application as a Potential Diagnostic Marker for Hepatocellular Carcinoma.

Publications

Development of a Chemiluminescence Immunoassay for Serum YB-1 and its Clinical Application as a Potential Diagnostic Marker for Hepatocellular Carcinoma.

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