Identification of Autophagy-Related Genes in the Progression from Non-Alcoholic Fatty Liver to Non-Alcoholic Steatohepatitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34262330", "kind": "science-record", "revision": 9, "content_hash": "sha256:3db83d2bd23180a1fce605baa67e845691a91d47eb7acee9a13b249ef9a52465", "created_at": "2026-11-01T15:41:43Z", "updated_at": "2026-11-01T22:47:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Autophagy-Related Genes in the Progression from Non-Alcoholic Fatty Liver to Non-Alcoholic Steatohepatitis.", "doi": "10.2147/IJGM.S317785", "pmid": "34262330", "authors": ["Mengyao Ma", "Wenhua Xie", "Xi Li"], "journal": "International journal of general medicine", "year": 2021, "abstract": "BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Autophagy plays a vital role in NAFLD development and progression. We aimed to establish a novel autophagy-related gene (ARG) signature as a therapeutic target in NAFLD patients based on high-throughput sequencing data.\nMETHODS: ARGs obtained from the HAMdb and high-sequencing data obtained from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed ARGs (DEARGs) between normal and NASH tissues. Then, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to explore potential biological and pathological functions of DEARGs. The protein-protein interaction (PPI) network of the DEARGs was established through the STRING website, and visualized by Cytoscape. In addition, hub genes were validated by an independent dataset GSE89632. Finally, we performed Gene Set Variation Analysis (GSVA) pathway-related analysis to identify the pivotal signaling pathways and genes for the progression of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH).\nRESULTS: A total of 76 DEARGs were identified in the GSE126848 dataset, of which 45 genes were upregulated and 31 genes were downregulated. GO analysis showed that the biological functions of DEARGs focused primarily on autophagy, cellular response to external stimulus, fibroblast proliferation, late endosome, and ubiquitin protein ligase binding. KEGG pathway analysis showed that these DEARGs were mainly involved in the apoptosis, PI3K-Akt signaling pathway, and estrogen signaling pathway. Among DEGs, 9 most closely related genes were identified from the PPI network. Furthermore, NOS3, IGF1, VAMP8, FOS, and HMOX1 were verified in the GSE89632 dataset. At last, the MAPK signal pathway was identified as important pathway, and JUN was identified as a key gene involved in the progression from NAFL to NASH.\nCONCLUSION: This study may provide credible molecular biomarkers in terms of screening and diagnosis for NAFLD. Meanwhile, it also serves as a basis for exploring the molecular mechanisms underlying the progression of NAFL to NASH.", "claims": [{"id": "claim-method", "statement": "The DEGs were determined between normal and NAFLD tissues in the GSE126848 dataset by using the “limma” R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34262330", "locator": "sections[4] \"Identification of DEARGs\" paragraph 2", "quote": "The DEGs were determined between normal and NAFLD tissues in the GSE126848 dataset by using the “limma” R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We obtained the RNA sequencing (RNA-seq) data (GSE126848 and GSE89632) of NAFLD through the GEO database (http://www.ncbi.nlm.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34262330", "locator": "sections[3] \"Data Acquisition\" paragraph 2", "quote": "We obtained the RNA sequencing (RNA-seq) data (GSE126848 and GSE89632) of NAFLD through the GEO database (http://www.ncbi.nlm.nih.gov/)."}], "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:34262330"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE126848"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE126848"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34262330", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S317785", "sha256": 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"−1.633130235", "0.000603545", "0.002927043"], ["ALPI", "−4.098624701", "−2.707234962", "0.013805642", "0.041945477"], ["FOS", "−1.035131218", "1.018454227", "0.015669374", "0.046612503"]], "row_count": 77, "column_count": 5, "numeric_cells": 313, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t0001"}}, {"id": "asset:table:pmid:34262330:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8f7d92e5fa07ed5d0ea70f9c6e85d08b6689996bbd335a1d1457a21b095a7bf8", "bytes": 2456, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#t0002", "version": null, "note": "The GO Enrichment Analysis (BP, MF, CC)", "structure": {"pmcid": "PMC8275104", "section_index": 11, "section_title": "Functional Enrichment of the DEARGs", "row_count": 12, "column_count": 10}, "table": {"label": "Table 2", "caption": "The GO Enrichment Analysis (BP, MF, CC)", 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