Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33578541", "kind": "science-record", "revision": 8, "content_hash": "sha256:5ed254a5034d6e962d252512413e58e2ad0de89515aaae917f68ecc3671e21d8", "created_at": "2026-11-01T15:41:25Z", "updated_at": "2026-11-01T22:46:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis.", "doi": "10.1097/MD.0000000000024471", "pmid": "33578541", "authors": ["Denghua Liu", "Rui Zhou", "Aiguo Zhou"], "journal": "Medicine", "year": 2021, "abstract": "BACKGROUND: In osteosarcoma, the lung is the most common metastatic organ. Intensive work has been made to illuminate the pathogeny, but the specific metastatic mechanism remains unclear. Thus, we conducted the study to seek to find the key genes and critical functional pathways associated with progression and treatment in lung metastasis originating from osteosarcoma.\nMETHODS: Two independent datasets (GSE14359 and GSE85537) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using DAVID. Meanwhile, the protein-protein interaction (PPI) network constructed by STRING was visualized using Cytoscape. Afterwards, the key module and hub genes were extracted from the PPI network using the MCODE and cytoHubba plugin. Moreover, the raw data obtained from GSE73166 and GSE21257 were applied to verify the expression differences and conduct the survival analyses of hub genes, respectively. Finally, the interaction network of miRNAs and hub genes constructed by ENCORI was visualized using Cytoscape.\nRESULTS: A total of 364 DEGs were identified, comprising 96 downregulated genes and 268 upregulated genes, which were mainly involved in cancer-associated pathways, adherens junction, ECM-receptor interaction, focal adhesion, MAPK signaling pathway. Subsequently, 10 hub genes were obtained and survival analysis demonstrated SKP2 and ASPM were closely related to poor prognosis of patients with osteosarcoma. Finally, hsa-miR-340-5p, has-miR-495-3p, and hsa-miR-96-5p were found to be most closely associated with these hub genes according to the interaction network of miRNAs and hub genes.\nCONCLUSION: The key genes and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of lung metastasis originating from osteosarcoma, and provide potential diagnostic and therapeutic targets.", "claims": [{"id": "claim-method", "statement": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r), a web-based application, contributes to filtrating DEGs through the Bioconductor's GEO Query and limma R software.[11] Therefore, in the present study, the DEGs between the lung metastasis group and the non-metastasis group were screened out by the GEO2R online platform with cut-off criteria of P < .05 and |log fold-change| (|logFC|) >1. The raw data of 2 gene expression microarray datasets (GSE14359, GSE85537) were obtained from the GEO database and then subjected to differential expression analysis by the GEO2R online platform.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33578541", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r), a web-based application, contributes to filtrating DEGs through the Bioconductor's GEO Query and limma R software.[11] Therefore, in the present study, the DEGs between the lung metastasis group and the non-metastasis group were screened out by the GEO2R online platform with cut-off criteria of P < .05 and |log fold-change| (|logFC|) >1."}, {"asset": "source:pmid:33578541", "locator": "sections[10] \"Identification of DEGs\" paragraph 2", "quote": "The raw data of 2 gene expression microarray datasets (GSE14359, GSE85537) were obtained from the GEO database and then subjected to differential expression analysis by the GEO2R online platform."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:33578541"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33578541", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000024471", "sha256": "sha256:13dabb7ea3c8df40776f989054467465f2a3c4f2c7896e82e161711303a681fd", "bytes": 28241, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1097/MD.0000000000024471", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7886415", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:33578541:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:ba1afb77726971e6e5df0ec527093bd31b2ed313094775229386ac6f1895ee27", "bytes": 2417, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T1", "version": null, "note": "The detailed information of hub genes.", "structure": {"pmcid": "PMC7886415", "section_index": 13, "section_title": "Hub gene selection and analysis", "row_count": 11, "column_count": 3}, "table": {"label": "Table 1", "caption": "The detailed information of hub genes.", "rows": [["Gene symbol", "Full name", "Function"], ["SKP2", "S-Phase kinase associated protein 2", "SKP2 encodes a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction, and transcription."], ["ASPM", "Abnormal spindle microtubule assembly", "ASPM encodes a centrosomal protein that plays an essential part in maintaining the normal function of the mitotic spindle and regulating neurogenesis."], ["TOP2A", "Topoisomerase (DNA) II alpha", "TOP2A encodes a DNA topoisomerase that is essential in the regulation of DNA structure and transcription, and it is the direct molecular target of anthacyclines."], ["SMC2", "Structural maintenance of chromosomes 2", "SMC2 encodes the central component of the condensin complex, which is required for conversion of interphase chromatin into mitotic-like condense chromosomes."], ["CDC25C", "Cell division cycle 25C", "CDC25C encoded a tyrosine protein phosphatase that participated in regulating G2/M progression and mediating DNA damage repair"], ["SOCS3", "Suppressor of cytokine signaling 3", "SOCS family proteins form part of a classical negative feedback system that mainly regulates cytokine signal transduction."], ["DTL", "Denticleless E3 ubiquitin protein ligase homolog", "DTL encodes a substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response, and translesion DNA synthesis"], ["ECT2", "Epithelial cell transforming 2", "ECT2 is a guanine nucleotide exchange factor (GEF) of the Rho family members of small GTPases and essential for signal transduction pathways involved in the regulation of cytokinesis."], ["CENPN", "Centromere protein N", "CENPN is the vital component of the CENPA-NAC (nucleosome-associated) complex, which plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation"], ["PARPBP", "PARP1 binding protein", "PARPBP contributes to suppressing inappropriate homologous recombination, thereby playing a central role in DNA repair and the maintenance of genomic stability."]], "row_count": 11, "column_count": 3, "numeric_cells": 7, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T1"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "reordered", "quote": "GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r), a web-based application, contributes to filtrating DEGs through the Bioconductor's GEO Query and limma R software.[11] Therefore, in the present study, the DEGs between the lung metastasis group and the non-metastasis group were screened out by the GEO2R online platform with cut-off criteria of P < .05 and |log fold-change| (|logFC|) >1. 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