Dataset Information

Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma.

ABSTRACT: Background: Hepatitis B virus infection had been identified its relationship with liver diseases, including liver tumors. We aimed to explore diagnostic and prognostic values between the Human Leukocyte Antigen (HLA) complex and hepatocellular carcinoma (HCC). Methods: We used the GSE14520 dataset to explore diagnostic and prognostic significance between HLA complex and HCC. A nomogram was constructed to predict survival probability of HCC prognosis. Gene set enrichment analysis was explored using gene ontologies and metabolic pathways. Validation of prognostic values of the HLA complex was performed in the Kaplan-Meier Plotter website. Results: We found that HLA-C showed the diagnostic value (P <0.0001, area under curve: 0.784, sensitivity: 93.14%, specificity: 62.26%). In addition, HLA-DQA1 and HLA-F showed prognostic values for overall survival, and HLA-A, HLA-C, HLA-DPA1 and HLA-DQA1 showed prognostic values for recurrence-free survival (all P ? 0.05, elevated 0.927, 0.992, 1.023, 0.918, 0.937 multiples compared to non-tumor tissues, respectively). Gene set enrichment analysis found that they were involved in antigen processing and toll like receptor signalling pathway, etc. The nomogram was evaluated for survival probability of HCC prognosis. Validation analysis indicated that HLA-C, HLA-DPA1, HLA-E, HLA-F and HLA-G were associated with HCC prognosis of overall survival (all P ? 0.05, elevated 0.988 and 0.997 multiples compared to non-tumor tissues, respectively). Conclusion: HLA-C might be a diagnostic and prognostic biomarker for HCC. HLA-DPA1 and HLA-F might be prognostic biomarkers for HCC.

SUBMITTER: Wang XK

PROVIDER: S-EPMC6775598 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma.

Wang Xiang-Kun XK Liao Xi-Wen XW Yang Cheng-Kun CK Yu Ting-Dong TD Liu Zheng-Qian ZQ Gong Yi-Zhen YZ Huang Ke-Tuan KT Zeng Xian-Min XM Han Chuang-Ye CY Zhu Guang-Zhi GZ Qin Wei W Peng Tao T

Journal of Cancer 20190828 21

<b>Background</b>: Hepatitis B virus infection had been identified its relationship with liver diseases, including liver tumors. We aimed to explore diagnostic and prognostic values between the Human Leukocyte Antigen (HLA) complex and hepatocellular carcinoma (HCC). <b>Methods</b>: We used the GSE14520 dataset to explore diagnostic and prognostic significance between HLA complex and HCC. A nomogram was constructed to predict survival probability of HCC prognosis. Gene set enrichment analysis wa ...[more]

PMID: 31602270

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Project description:Primary liver cancer is a rapidly progressing neoplasm with high morbidity and mortality rates. The present study aimed to identify potential diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus (HBV)-associated early stage hepatocellular carcinoma (HCC). The gene expression profiles were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), hub genes and the enrichment of signaling pathways were filtered out via a high-throughput sequencing method. The association between hub genes and the effects of the abnormal expression of hub genes on the rate of genetic variation, overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DSS) of patients with HCC, as well as pathological stage and grade, were analyzed using different databases. A total of 1,582 DEGs were identified. Gene Ontology analysis revealed that the DEGs were mainly involved in the 'oxidation-reduction process', 'steroid metabolic process', 'metabolic process' and 'fatty acid beta-oxidation'. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways revealed that the DEGs were mainly associated with 'metabolic pathways', 'PPAR signaling pathway', 'fatty acid degradation' and the 'cell cycle'. A total of 8 hub genes were extracted. Additionally, the abnormal expression levels of hub genes were closely associated with the OS, RFS, PFS and DSS of patients, the pathological stage and the grade. Furthermore, abnormal expression levels of the 8 hub genes were found in >30% of all samples. Several small molecular compounds that may reverse the altered DEGs were identified based on Connectivity Map analysis, including phenoxybenzamine, GW-8510, resveratrol, 0175029-0000 and daunorubicin. In conclusion, the dysfunction of fat metabolic pathways, the cell cycle, oxidation-reduction processes and viral carcinogenesis may serve critical roles in the occurrence of HBV-associated early stage HCC. The identified 8 hub genes may act as robust biomarkers for diagnosis and prognosis. Some small molecular compounds may be promising targeted agents against HBV-associated early stage 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.

Dataset Information

Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma.

Publications

Diagnostic and prognostic biomarkers of Human Leukocyte Antigen complex for hepatitis B virus-related hepatocellular carcinoma.

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