Bioinformatics analysis and experimental validation of a novel autophagy-related signature relevant to immune infiltration for recurrence prediction after curative hepatectomy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37014321", "kind": "science-record", "revision": 3, "content_hash": "sha256:72abeaad4557fc03855982114f1e79e1dda831eef961be9a30c17bb30a2ab975", "created_at": "2026-11-01T19:01:40Z", "updated_at": "2026-11-01T22:09:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analysis and experimental validation of a novel autophagy-related signature relevant to immune infiltration for recurrence prediction after curative hepatectomy.", "doi": "10.18632/aging.204632", "pmid": "37014321", "authors": ["Huaxiang Wang", "Chengkai Yang", "Dong Li", "Ruling Wang", "Yanbing Li", "Lizhi Lv"], "journal": "Aging", "year": 2023, "abstract": "Hepatocellular carcinoma (HCC) remains imposing an enormous economic and healthcare burden worldwide. In this present study, we constructed and validated a novel autophagy-related gene signature to predict the recurrence of HCC patients. A total of 29 autophagy-related differentially expressed genes were identified. A five-gene signature (CLN3, HGF, TRIM22, SNRPD1, and SNRPE) was constructed for HCC recurrence prediction. Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients both in the training set (GSE14520 dataset) and the validation set (TCGA and GSE76427 dataset). Multivariate cox regression analysis demonstrated that the 5-gene signature was an independent risk factor for recurrence-free survival (RFS) in HCC patients. The nomograms incorporating 5-gene signature and clinical prognostic risk factors were able to effectively predict RFS. KEGG and GSEA analysis revealed that the high-risk group was enriched with multiple oncology characteristics and invasive-related pathways. Besides, the high-risk group had a higher level of immune cells and higher levels of immune checkpoint-related gene expression in the tumor microenvironment, suggesting that they might be more likely to benefit from immunotherapy. Finally, the immunohistochemistry and cell experiments confirmed the role of SNRPE, the most significant gene in the gene signature. SNRPE was significantly overexpressed in HCC. After SNRPE knockdown, the proliferation, migration and invasion ability of the HepG2 cell line were significantly inhibited. Our study established a novel five-gene signature and nomogram to predict RFS of HCC, which may help in clinical decision-making for individual treatment.", "claims": [{"id": "claim-method", "statement": "We conducted the Univariate and Multivariate Cox proportional hazards regression mode on differential expressed ARGs to identify the gene that independently predict the RFS of HCC patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37014321", "locator": "sections[16] \"Construction and validation of the autophagy-related gene signature\" paragraph 2", "quote": "We conducted the Univariate and Multivariate Cox proportional hazards regression mode on differential expressed ARGs to identify the gene that independently predict the RFS of HCC patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and TCGA database (https://portal.gdc.cancer.gov).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37014321", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "The datasets generated for this study can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and TCGA database (https://portal.gdc.cancer.gov)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients both in the training set (GSE14520 dataset) and the validation set (TCGA and GSE76427 dataset).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37014321", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients both in the training set (GSE14520 dataset) and the validation set (TCGA and GSE76427 dataset)."}, {"asset": "source:pmid:37014321", "locator": "sections[6] \"Validation of the prognostic five-gene signature in two validation sets\" paragraph 2", "quote": "In the GSE76427 dataset, the AUCs of 1-, 3-, and 5-year RFS were 0.81, 0.91, and 0.93, respectively (Figure 3E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Patients in high-risk groups exhibited a significantly poor prognosis compared with low-risk patients both in the training set (GSE14520 dataset) and the validation set (TCGA and GSE76427 dataset).", "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:37014321"], "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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Finally, the immunohistochemistry and cell experiments confirmed the role of S"], "order_basis": "paper_text_order:1420", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nificantly overexpressed in HCC. After SNRPE knockdown, the proliferation, migration and invasion a", "relevant articles [49, 50]. Cell culture and transfection The normal hepatocyte cell line LO2 and HCC", "here of 5% CO2 at 37°C. The HepG2 cells were transfected with shSNRPE or sh-NC using Lipofectamine™ 3", "h shSNRPE or sh-NC using Lipofectamine™ 3000 Transfection Kit (L3000015, Invitrogen, USA), according t"], "order_basis": "paper_text_order:1597", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ation, migration and invasion ability of the HepG2 cell line were significantly inhibited. Our", "se Academy of Sciences (Shanghai, China). We cultured these cell lines in DMEM (Gibco) supplemente", "ocyte cell line LO2 and HCC cell lines Huh7, HepG2, Hep3B were obtained from the Chinese Type C", "er a moist atmosphere of 5% CO2 at 37°C. 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