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pmid:32552682
The significance of m6A RNA methylation regulators in predicting the prognosis and clinical course of HBV-related hepatocellular carcinoma.
Qiongxuan Fang · Hongsong Chen
Molecular medicine (Cambridge, Mass.) · 2020 doi:10.1186/s10020-020-00185-z
Paper
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Experiment
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Data
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Complete file
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Thus, we constructed an m6A-related model that may enhance HBV-related HCC prognosis.\nMETHODS: Gene signatures of HNRNPA2B1 and RBM15 were generated by univariate and Lasso Cox regression analyses using the gene set and clinical information from The Cancer Genome Atlas (TCGA) database. High-risk and low-risk groups were confirmed based on the gene signature model. Furthermore, we validated the predictive roles of the two genes for overall survival (OS) in the GSE14520 dataset. The relative expression of 22 paired mRNAs was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis to determine whether the two genes had a predictive role in our Guilin cohort.\nRESULTS: The differences in OS between the high-risk and low-risk groups were statistically significant in the TCGA (p = 0.003) and GSE14520 (p = 0.045) datasets, but not in the Guilin cohort, owing to differences in clinical information among the three cohorts (mainly the TNM stage and survival state). Stratified analysis of TNM stages showed that the two-gene signature acted as a prognostic indicator of HBV-related HCC patients in the early TNM stage; both TCGA and GSE14520 cohorts showed statistical significance. Moreover, multivariate Cox regression analysis indicated that the two-gene signature was an independent factor for predicting prognosis (HR = 1.087, 95% CI: 1.007-1.172). Correlation analysis between the gene signature and clinical features revealed that the risk stratification was significantly correlated with grade and survival state. Finally, Gene Set Enrichment Analysis (GSEA) revealed that the KEGG pathways associated with the cell cycle, DNA replication, the spliceosome, repair, and metabolism-related processes were all significantly enriched in the high-risk group. Among the enriched genes, the expression levels of the replication protein RPA1 and the pre-mRNA splicing factor SF3B1 were significantly upregulated in the high-risk group. These results might help in elucidating the underlying molecular mechanisms of HBV-related HCC.\nCONCLUSIONS: Our data may provide new predictive signatures and potential therapeutic targets to identify and treat HBV-related HCC patients in the early disease stage.", "claims": [{"id": "claim-method", "statement": "We performed univariate and multivariate Cox regression analysis to confirm whether the two-gene signature could be an independent prognostic factor for patients with HBV-related HCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32552682", "locator": "sections[14] \"Independent prognostic role of the gene signature\" paragraph 2", "quote": "We performed univariate and multivariate Cox regression analysis to confirm whether the two-gene signature could be an independent prognostic factor for patients with HBV-related HCC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data not included in the manuscript is available from the supplementary materials.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32552682", "locator": "sections[25] \"Availability of data and materials\" paragraph 2", "quote": "All data not included in the manuscript is available from the supplementary materials."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:32552682"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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