A Novel and Robust Prognostic Model for Hepatocellular Carcinoma Based on Enhancer RNAs-Regulated Genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35646665", "kind": "science-record", "revision": 4, "content_hash": "sha256:3025fd2c69fbcbe6e87c902b68e82e8e9c2e1108d8f7f6fef8966b046c1a0745", "created_at": "2026-11-01T18:14:34Z", "updated_at": "2026-11-01T22:06:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel and Robust Prognostic Model for Hepatocellular Carcinoma Based on Enhancer RNAs-Regulated Genes.", "doi": "10.3389/fonc.2022.849242", "pmid": "35646665", "authors": ["Wei Zhang", "Kegong Chen", "Wei Tian", "Qi Zhang", "Lin Sun", "Yupeng Wang", "Meina Liu", "Qiuju Zhang"], "journal": "Frontiers in oncology", "year": 2022, "abstract": "Evidence has demonstrated that enhancer RNAs (eRNAs) play a vital role in the progression and prognosis of cancers, but few studies have focused on the prognostic ability of eRNA-regulated genes (eRGs) for hepatocellular carcinoma (HCC). Using gene expression profiles of HCC patients from the TCGA-LIHC and eRNA expression profiles from the enhancer RNA in cancers (eRic) data portal, we developed a novel and robust prognostic signature composed of 10 eRGs based on Lasso-penalized Cox regression analysis. According to the signature, HCC patients were stratified into high- and low-risk groups, which have been shown to have significant differences in tumor immune microenvironment, immune checkpoints, HLA-related genes, DNA damage repair-related genes, Gene-set variation analysis (GSVA), and the lower half-maximal inhibitory concentration (IC50) of Sorafenib. The prognostic nomogram combining the signature, age, and TNM stage had good predictive ability in the training set (TCGA-LIHC) with the concordance index (C-index) of 0.73 and the AUCs for 1-, 3-, and 5-year OS of 0.82, 0.77, 0.74, respectively. In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively. In addition, an important eRG (AKR1C3) was validated using two HCC cell lines (Huh7 and MHCC-LM3) in vitro, and the results demonstrated the overexpression of AKR1C3 is related to cell proliferation, migration, and invasion in HCC. Altogether, our eRGs signature and nomogram can predict prognosis accurately and conveniently, facilitate individualized treatment, and improve prognosis for HCC patients.", "claims": [{"id": "claim-method", "statement": "Subsequently, Lasso-penalized Cox regression analysis was performed to build the prognostic eRGs signature, and 10-fold cross-validation was carried out to determine the optimal penalty parameter using “glmnet” package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35646665", "locator": "sections[4] \"2.2 Construction and Validation of eRGs Signature\" paragraph 4", "quote": "Subsequently, Lasso-penalized Cox regression analysis was performed to build the prognostic eRGs signature, and 10-fold cross-validation was carried out to determine the optimal penalty parameter using “glmnet” package in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/); enhancer RNA in cancers (eRic) (https://hanlab.uth.edu/eRic/); Gene Expression Omnibus, GSE14520 -GPL3921.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35646665", "locator": "sections[27] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/); enhancer RNA in cancers (eRic) (https://hanlab.uth.edu/eRic/); Gene Expression Omnibus, GSE14520 -GPL3921."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35646665", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In external validation set (GSE14520), the nomogram also performed well with the C-index of 0.71 and the AUCs for 1-, 3-, and 5-year OS of 0.74, 0.77, 0.74, respectively.", "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:35646665"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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