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pmid:30918751
Identification of an eight-gene signature for survival prediction for patients with hepatocellular carcinoma based on integrated bioinformatics analysis.
Guo-Jie Qiao · Liang Chen · Jin-Cai Wu · Zhou-Ri Li
PeerJ · 2019 doi:10.7717/peerj.6548
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Experiment
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Complete file
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Despite recent advances in imaging techniques and therapeutic intervention for HCC, the low overall 5-year survival rate of HCC patients remains unsatisfactory. This study aims to find a gene signature to predict clinical outcomes in HCC.\nMETHODS: Bioinformatics analysis including Cox's regression analysis, Kaplan-Meier (KM) and receiver operating characteristic curve (ROC) analysis and the random survival forest algorithm were performed to mine the expression profiles of 553 hepatocellular carcinoma (HCC) patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public database.\nRESULTS: We selected a signature comprising eight protein-coding genes (DCAF13, FAM163A, GPR18, LRP10, PVRIG, S100A9, SGCB, and TNNI3K) in the training dataset (AUC = 0.77 at five years, n = 332). The signature stratified patients into high- and low-risk groups with significantly different survival in the training dataset (median 2.20 vs. 8.93 years, log-rank test P < 0.001) and in the test dataset (median 2.68 vs. 4.24 years, log-rank test P = 0.004, n = 221, GSE14520). Further multivariate Cox regression analysis showed that the signature was an independent prognostic factor for patients with HCC. Compared with TNM stage and another reported three-gene model, the signature displayed improved survival prediction power in entire dataset (AUC signature = 0.66 vs. AUC TNM = 0.64 vs. AUC gene model = 0.60, n = 553). Stratification analysis shows that it can be used as an auxiliary marker for many traditional staging models.\nCONCLUSIONS: We constructed an eight-gene signature that can be a novel prognostic marker to predict the survival of HCC patients.", "claims": [{"id": "claim-method", "statement": "Then, univariate Cox and multivariate Cox regression analyses were performed in the training dataset and showed that the PCG signature was an independent prognostic factor after adjusting for other clinical features, including sex, age and pTNM (high-risk group vs. low-risk group, HR = 7.23, 95% CI [4.19–12.47], P < 0.001, n = 332, Table 3).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30918751", "locator": "sections[13] \"The PCG signature is an independent prognostic factor\" paragraph 2", "quote": "Then, univariate Cox and multivariate Cox regression analyses were performed in the training dataset and showed that the PCG signature was an independent prognostic factor after adjusting for other clinical features, including sex, age and pTNM (high-risk group vs. low-risk group, HR = 7.23, 95% CI [4.19–12.47], P < 0.001, n = 332, Table 3)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe dataset with mRNA expression profiling and clinical information was taken from GEO: GSE14520.\nThe dataset including gene expression profile and associated corresponding clinical information of patients analysed in this study was downloaded from The Cancer Genome Atlas (TCGA, http://cancergenome.nih.gov/):\nLiver cancer data: https://xenabrowser.net/datapages/?cohort=GDC%20TCGA%20Liver%20Cancer%20(LIHC)\nFPKM: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.htseq_fpkm.tsv.gz\nClinical data, survival data: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.survival.tsv.gz\nPhenotype: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.GDC_phenotype.tsv.gz.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30918751", "locator": "sections[30] \"Data Availability Statement\" paragraphs 1-8", "quote": "The following information was supplied regarding data availability:\nThe dataset with mRNA expression profiling and clinical information was taken from GEO: GSE14520.\nThe dataset including gene expression profile and associated corresponding clinical information of patients analysed in this study was downloaded from The Cancer Genome Atlas (TCGA, http://cancergenome.nih.gov/):\nLiver cancer data: https://xenabrowser.net/datapages/?cohort=GDC%20TCGA%20Liver%20Cancer%20(LIHC)\nFPKM: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.htseq_fpkm.tsv.gz\nClinical data, survival data: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.survival.tsv.gz\nPhenotype: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.GDC_phenotype.tsv.gz."}], "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:30918751"], "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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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE14520"], "resolved_accessions": ["GSE14520"], "statements": ["The following information was supplied regarding data availability:\nThe dataset with mRNA expression profiling and clinical information was taken from GEO: GSE14520.\nThe dataset including gene expression profile and associated corresponding clinical information of patients analysed in this study was downloaded from The Cancer Genome Atlas (TCGA, http://cancergenome.nih.gov/):\nLiver cancer data: https://xenabrowser.net/datapages/?cohort=GDC%20TCGA%20Liver%20Cancer%20(LIHC)\nFPKM: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.htseq_fpkm.tsv.gz\nClinical data, survival data: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.survival.tsv.gz\nPhenotype: https://gdc.xenahubs.net/download/TCGA-LIHC/Xena_Matrices/TCGA-LIHC.GDC_phenotype.tsv.gz."], "basis": "The paper names GSE14520 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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