Exploring Potential Biomarkers, Ferroptosis Mechanisms, and Therapeutic Targets Associated with Cutaneous Squamous Cell Carcinoma via Integrated Transcriptomic Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36247089", "kind": "science-record", "revision": 5, "content_hash": "sha256:b2debcd1dd8c7f9dc66afde924b32a3107abbd1c38531600bb69d2737591be26", "created_at": "2026-11-01T18:15:38Z", "updated_at": "2026-11-01T22:50:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exploring Potential Biomarkers, Ferroptosis Mechanisms, and Therapeutic Targets Associated with Cutaneous Squamous Cell Carcinoma via Integrated Transcriptomic Analysis.", "doi": "10.1155/2022/3524022", "pmid": "36247089", "authors": ["Wenxing Su", "Biao Huang", "Qingyi Zhang", "Wei Han", "Lu An", "Yi Guan", "Jiang Ji", "Daojiang Yu"], "journal": "Journal of healthcare engineering", "year": 2022, "abstract": "Background: Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with nonmelanoma skin cancers (NMSC). However, the unclear pathogenesis of cSCC limits the application of molecular targeted therapy.\nMethods: Three microarray datasets (GSE2503, GSE45164, and GSE66359) were downloaded from the Gene Expression Omnibus (GEO). After identifying the differentially expressed genes (DEGs) in tumor and nontumor tissues, five kinds of analyses, namely, functional annotation, protein-protein interaction (PPI) network, hub gene selection, TF-miRNA-mRNA regulatory network analysis, and ferroptosis mechanism, were performed.\nResults: A total of 146 DEGs were identified with significant differences, including 113 upregulated genes and 33 downregulated genes. The enriched functions and pathways of the DEGs included microtubule-based movement, ATP binding, cell cycle, P53 signaling pathway, oocyte meiosis, and PLK1 signaling events. Nine hub genes were identified (CDK1, AURKA, RRM2, CENPE, CCNB1, KIAA0101, ZWINT, TOP2A, and ASPM). Finally, RRM2, AURKA, and SAT1 were identified as significant ferroptosis-related genes in cSCC. The differential expression of these genes has been verified in two other independent datasets.\nConclusions: By integrated bioinformatic analysis, the hub genes identified in this study elucidated the molecular mechanism of the pathogenesis and progression of cSCC and are expected to become future biomarkers or therapeutic targets.", "claims": [{"id": "claim-method", "statement": "The DEGs between cSCC and noncancerous samples were screened using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), which is an online tool for differential analysis of the original dataset based on the LIMMA software package [16].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36247089", "locator": "sections[4] \"2.2. Identification of DEGs\" paragraph 2", "quote": "The DEGs between cSCC and noncancerous samples were screened using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), which is an online tool for differential analysis of the original dataset based on the LIMMA software package [16]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36247089", "locator": "sections[23] \"Data Availability\" paragraph 2", "quote": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 146 common DEGs, including 113 upregulated genes and 33 downregulated genes, were identified between cSCC tissues and normal tissues.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36247089", "locator": "sections[12] \"3.1. Identification of DEGs in cSCC\" paragraph 2", "quote": "As shown in Figure 3(a), a total of 146 common DEGs, including 113 upregulated genes and 33 downregulated genes, were finally identified between cSCC tissues and normal tissues."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 146 common DEGs, including 113 upregulated genes and 33 downregulated genes, were identified between cSCC tissues and normal tissues.", "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:36247089"], "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:GSE2503"], "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:GSE2503"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36247089", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/3524022", "sha256": "sha256:3d34ece018e245bde8d9fb887ee5a63f34fd100c1fd0ce377a7fa1182350b0b2", "bytes": 42239, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/3524022", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9553755", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE2503", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2503", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE2503", "version": null, "note": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM47612", "GSM47613", "GSM47614", "GSM47615", "GSM47616", "GSM47617", "GSM47618", "GSM47619", "GSM47620", "GSM47621", "GSM47622", "GSM47623", "GSM47624", "GSM47625", "GSM47626"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Novel Molecular Markers for non-melanoma skin cancer", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE45164", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45164", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE45164", "version": null, "note": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1098446", "GSM1098447", "GSM1098448", "GSM1098449", "GSM1098450", "GSM1098451", "GSM1098452", "GSM1098453", "GSM1098454", "GSM1098455", "GSM1098456", "GSM1098457", "GSM1098458"], "sample_count": 13, "group_sizes": null, "group_sizes_basis": null, "platform": "571", "taxon": "Homo sapiens", "title": "Transcription profiling of human skin squamous cell carcinoma (SCC)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE53462", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53462", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE53462", "version": null, "note": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1294012", "GSM1294013", "GSM1294014", "GSM1294015", "GSM1294016", "GSM1294017", "GSM1294018", "GSM1294019", "GSM1294020", "GSM1294021", "GSM1294022", "GSM1294023", "GSM1294024", "GSM1294025", "GSM1294026", "GSM1294027", "GSM1294028", "GSM1294029", "GSM1294030", "GSM1294031", "GSM1294032", "GSM1294033", "GSM1294034", "GSM1294035", "GSM1294036", "GSM1294037"], "sample_count": 26, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Molecular classification of non-melanoma skin cancer by gene expression profiling", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE66359", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66359", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE66359", "version": null, "note": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1620805", "GSM1620806", "GSM1620807", "GSM1620808", "GSM1620809", "GSM1620810", "GSM1620811", "GSM1620812", "GSM1620813", "GSM1620814", "GSM1620815", "GSM1620816", "GSM1620817"], "sample_count": 13, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Analysis of the gene expression profile in normal human epidermal keratinocytes and cutaneous squamous cell carcinoma cell lines", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE7553", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE7553", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE7553", "version": null, "note": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM183218", "GSM183219", "GSM183220", "GSM183221", "GSM183222", "GSM183223", "GSM183224", "GSM183225", "GSM183226", "GSM183227", "GSM183228", "GSM183229", "GSM183230", "GSM183231", "GSM183232", "GSM183233", "GSM183234", "GSM183235", "GSM183236", "GSM183237", "GSM183238", "GSM183239", "GSM183240", "GSM183241", "GSM183242", "GSM183243", "GSM183244", "GSM183245", "GSM183246", "GSM183247", "GSM183248", "GSM183249", "GSM183250", "GSM183251", "GSM183252", "GSM183253", "GSM183254", "GSM183255", "GSM183256", "GSM183257", "GSM183258", "GSM183259", "GSM183260", "GSM183261", "GSM183262", "GSM183263", "GSM183264", "GSM183265", "GSM183266", "GSM183267", "GSM183268", "GSM183269", "GSM183270", "GSM183271", "GSM183272", "GSM183273", "GSM183274", "GSM183275", "GSM183276", "GSM183277", "GSM183278", "GSM183279", "GSM183280", "GSM183281", "GSM183282", "GSM183283", "GSM183284", "GSM183285", "GSM183286", "GSM183287", "GSM183288", "GSM183289", "GSM183290", "GSM183291", "GSM183292", "GSM183293", "GSM183294", "GSM183295", "GSM183296", "GSM183297", "GSM183298", "GSM183299", "GSM183300", "GSM183301", "GSM183302", "GSM183303", "GSM183304"], "sample_count": 87, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene Expression Patterns Involved in the Malignant Transformation and Progression of Metastatic Melanoma", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE2503 not downloaded", "asset:data:geo:GSE2503 licence not read", "asset:data:geo:GSE45164 not downloaded", "asset:data:geo:GSE45164 licence not read", "asset:data:geo:GSE53462 not downloaded", "asset:data:geo:GSE53462 licence not read", "asset:data:geo:GSE66359 not downloaded", "asset:data:geo:GSE66359 licence not read", "asset:data:geo:GSE7553 not downloaded", "asset:data:geo:GSE7553 licence not read"]}, "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": "verbatim", "quote": "The DEGs between cSCC and noncancerous samples were screened using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), which is an online tool for differential analysis of the original dataset based on the LIMMA software package [16]."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE2503", "GSE45164", "GSE66359", "GSE53462", "GSE7553"], "resolved_accessions": ["GSE2503", "GSE45164", "GSE66359", "GSE53462", "GSE7553"], "statements": ["In this study, mRNA microarray datasets were downloaded from the Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo)."], "basis": "The paper names GSE2503, GSE45164, GSE66359, GSE53462, GSE7553 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36247089", "data:geo:GSE2503"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE2503"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:11:14Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13363, "completion_tokens": 1710, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36247089", "type": "paper", "label": "pmid:36247089"}, {"id": "source:pmid:36247089", "type": "manuscript", "label": "PMID 36247089 full text"}, {"id": "data:geo:GSE2503", "type": "dataset", "label": "GEO GSE2503"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36247089", "type": "paper", "label": "pmid:36247089"}, {"id": "source:pmid:36247089", "type": "manuscript", "label": "PMID 36247089 full text"}, {"id": "data:geo:GSE2503", "type": "dataset", "label": "GEO GSE2503"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36247089", "type": "extraction", "used": ["source:pmid:36247089"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE2503", "type": "accession_resolution", "used": ["data:geo:GSE2503"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36247089", "parent_hash": "sha256:fe567124b22bf4ad8c1959314edb912bbd354416b75a4c4d2ca39caae83f8ccd", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE2503 licence not read", "asset:data:geo:GSE2503 not downloaded", "asset:data:geo:GSE45164 licence not read", "asset:data:geo:GSE45164 not downloaded", "asset:data:geo:GSE53462 licence not read", "asset:data:geo:GSE53462 not downloaded", "asset:data:geo:GSE66359 licence not read", "asset:data:geo:GSE66359 not downloaded", "asset:data:geo:GSE7553 licence not read", "asset:data:geo:GSE7553 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["f molecular targeted therapy. Methods: Three microarray datasets (GSE2503, GSE45164, and GSE66359) w"], "order_basis": "paper_text_order:369", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The DEGs between cSCC and noncancerous samples were screened using GEO2R (https://www.ncbi.nlm.nih.gov/geo/geo2r), which is an online tool for differential analysis of the original dataset based on the LIMMA software package [16]."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}