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Serum microRNA profiles as prognostic biomarkers for HBV-positive hepatocellular carcinoma.

ABSTRACT: To establish serum microRNA profiles as prognostic biomarkers in hepatocellular carcinoma patients (HCCs), we used deep sequencing to screen serum microRNAs in a discovery set .Twelve up-regulated serum miRNAs were selected for qPCR analysis in a training set. MiR-192-5p and miR-29a-3p were identified and associated with HCC prognosis. HCCs with high concentrations of miR-192-5p and miR-29a-3p had poorer overall survival (OS) and progression-free survival (PFS) than those with low concentrations. We calculated a prognostic index (PI) score and classified patients into low-, medium- and high-risk groups. OS and PFS among the 3 groups from the training set were significantly different (all P < 0.05). PI (PIOS, PIPFS) score was the only independent prognostic predictor for OS and PFS of HCCs in the training set. These results were further confirmed in a validation set. In conclusion, differentially expressed serum miRNAs can be helpful for predicting survival in HCCs.

SUBMITTER: Zhu HT

PROVIDER: S-EPMC5216748 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Serum microRNA profiles as prognostic biomarkers for HBV-positive hepatocellular carcinoma.

Zhu Hao-Tu HT Hasan Abdulbaqi M E AM Liu Rong-Bin RB Zhang Zi-Chen ZC Zhang Xiao X Wang Jing J Wang Hai-Yun HY Wang Fang F Shao Jian-Yong JY

Oncotarget 20160701 29

To establish serum microRNA profiles as prognostic biomarkers in hepatocellular carcinoma patients (HCCs), we used deep sequencing to screen serum microRNAs in a discovery set .Twelve up-regulated serum miRNAs were selected for qPCR analysis in a training set. MiR-192-5p and miR-29a-3p were identified and associated with HCC prognosis. HCCs with high concentrations of miR-192-5p and miR-29a-3p had poorer overall survival (OS) and progression-free survival (PFS) than those with low concentrations ...[more]

PMID: 27317768

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Project description:BackgroundHepatocellular carcinoma closely related to metabolic disorders is a common and aggressive liver malignancy. The dysregulation of bile acid homeostasis has emerged as a key factor for the development and progression of HCC. We aimed to investigate the relationship between bile acids and HCC diagnosis and progression.MethodsA total of 744 HBV-related patients (including 396 HCC patients and 348 patients with chronic liver diseases) were enrolled in the current study. The baseline characteristics of patients were collected from electronic medical records, and the levels of bile acid profiles were determined by LC-MS/MS. Propensity score matching analysis was conducted to reduce the effect of selection bias, and receiver operating characteristic analysis was performed to evaluate the clinical application values of bile acid.ResultsSignificant differences were observed for most characteristics between the HCC group and the CLD group before PSM analysis. Patients with HCC were older and fatter (p < 0.05). After adjusting with a 1:1 ratio for age, gender and BMI, 42 HCC patients and 42 non-HCC patients were matched in 2 groups, respectively. The total bile acid level in HCC patients was lower than that in patients with chronic liver diseases before and after PSM analysis (p < 0.05). However, patients with HCC had significantly higher levels of DCA, LCA, and GLCA and lower levels of TCDCA, GUDCA, and TUDCA (p < 0.05, respectively). Besides, the TCDCA, TUDCA, GLCA, and GUDCA were significantly correlated with tumor procession. Moreover, the BAs profiles had a superior predictive ability for predicting the development of HCC even in patients with low serum AFP levels.ConclusionPatients with HCC had significantly lower levels of total bile acid, but higher levels of secondary bile acids (DCA, LCA, and GLCA). The levels of primary bile acid (TCDCA) were closely related to tumor size and stage, which indicated that the bile acids were involved in the HCC procession and had important clinical application values.

Project description:MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC.To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software.Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection.Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC.

Project description:BackgroundThe aim of the present study was to develop an improved diagnostic and prognostic model for HBV-associated HCC by combining AFP with PIVKA-II and other potential serum/plasma protein biomarkers.MethodsA total of 578 patients, including 352 patients with HBV-related HCC, 102 patients with HBV-associated liver cirrhosis (LC), 124 patients with chronic HBV, and 127 healthy subjects (HS), were enrolled in the study. The serum levels of AFP, PIVKA-II, and other laboratory parameters were collected. Univariate and multivariate logistic regression and Cox regression analyses were performed to identify independent diagnostic and prognostic factors, respectively. The diagnostic efficacy of the nomogram was evaluated using receiver operator curve (ROC) analysis and the prognostic performance was measured by Harrell's concordance index (C-index).ResultsAFP and PIVKA-II levels were significantly increased in HBV-related HCC, compared with those in HBV-associated LC and chronic HBV participants (p < 0.05 and p < 0.001, respectively). The diagnostic nomogram, which included age, gender, AFP, PIVKA-II, prothrombin time (PT), and total protein (TP), discriminated patients with HBV-HCC from those with HBV-LC or chronic HBV with an AUC of 0.970. In addition, based on the univariate and multivariate Cox regression analysis, PIVKA-II, γ-glutamyl transpeptidase, and albumin were found to be significantly associated with the prognosis of HBV-related HCC and were incorporated into a nomogram. The C-index of the nomogram for predicting 3-year survival in the training and validation groups was 0.75 and 0.78, respectively. The calibration curves for the probability of 3-year OS showed good agreement between the nomogram prediction and the actual observation in the training and the validation groups. Furthermore, the nomogram had a higher C-index (0.74) than that of the Child-Pugh grade (0.62), the albumin-bilirubin (ALBI) score (0.64), and Barcelona Clinic Liver Cancer (0.56) in all follow-up cases.ConclusionOur study suggests that the nomograms based on AFP, PIVKA-II, and potential serum protein biomarkers showed a better performance in the diagnosis and prognosis of HCC, which may help to guide therapeutic strategies and assess the prognosis of HCC.

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Serum microRNA profiles as prognostic biomarkers for HBV-positive hepatocellular carcinoma.

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Serum microRNA profiles as prognostic biomarkers for HBV-positive hepatocellular carcinoma.

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